# NMDA antagonists for tolerance, a collection of the evidence and anecdotal reports



## MeDieViL

I tought id make this thread for those interested in using NMDA antagonists for drug tolerance.


*NMDAR and opioid tolerance:*

(PMID: 19806811) Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice
_From these results it is concluded that lamotrigine and magnesium sulfate alone or in combination could prevent the development of morphine tolerance and withdrawal symptoms. Glutamate release inhibitory effect of lamotrigine and its possible mechanism and property of magnesium, blocking the N-Methyl-D-Aspartate (NMDA) receptor calcium channel, is probably its mechanism on preventing morphine induced tolerance and dependence._

(PMID: 19764437) Anti-opioid action of glutamate-NMDA receptor systems underlying morphine analgesic tolerance
_The mechanisms underlying opioid tolerance are not fully understood, but appear to be comprised of two types of plasticity or counter-adaptation, at the cellular level and through neuronal circuits. Current studies mostly emphasize the cellular adaptation mechanisms, which include altered gene expression and receptor desensitization due to phosphorylation and endocytosis. However, the mechanisms underlying opioid tolerance and dependence are not always explained by cellular adaptation mechanisms alone. This review focuses on the plasticity in neuronal circuits achieved through an enhancement of so-called anti-opioid glutamate/NMDA receptor synaptic activities._

(PMID: 18819620) Evaluation the effects of dextromethorphan and midazolam on morphine induced tolerance and dependence in mice.
_From these results it may concluded that Dextromethorphan and midazolam alone or in combination could prevent the development of morphine induced tolerance and dependence. These effects can be related to the N-Methyl-D-Aspartate (NMDA) receptor antagonist behavior of Dextromethorphan and GABA-receptor agonist property of midazolam._

(PMID: 18177675) The glycine site-specific NMDA antagonist (+)-HA966 enhances the effect of morphine and reverses morphine tolerance via a spinal mechanism
_Using the C-fibre reflex as a nociceptive response elicited by a wide range of stimulus intensities in the rat, we recently reported that a single treatment with (+)-HA966, a glycine site-specific NMDA receptor antagonist: (1) potentiates morphine antinociception; and (2) reverses an established morphine tolerance. _

(PMID: 17994223) NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats
_CONCLUSIONS: The results, together with previous research, suggest that NMDA receptors are broadly involved in opiate-induced plasticity, including the development of opiate tolerance and sensitization._

*NMDAR and ethanol tolerance:*

(PMID: 1596749) Effect of (+)MK-801 and ketamine on rapid tolerance to ethanol
_The findings suggest that NMDA antagonists block rapid tolerance by preventing some adaptation that occurs during intoxicated practice._

(PMID: 1831064) NMDA antagonist inhibits rapid tolerance to ethanol
_These data suggest that the known role of NMDA receptors in long-term synaptic facilitation may underlie the effect of learning in the development of tolerance to the motor-impairing and hypothermic effects of ethanol._

(PMID: 16790637) Ethanol-induced hypnotic tolerance is absent in N-methyl-D-aspartate receptor epsilon 1 subunit knockout mice
_Our results indicate epsilon1 subunit containing the NMDA receptor might be involved in the development of ethanol-induced hypnotic tolerance._

(PMID: 15153783) Acute tolerance to ethanol inhibition of NMDA-induced responses in rat rostral ventrolateral medulla neurons
_These data suggested that ethanol inhibition and subsequent tolerance development is associated with changed sensitivity to NMDA in the RVLM, which may play important roles in the ethanol regulation of cardiovascular function. _

(PMID: 8724445) Dizocilpine prevents the development of tolerance to ethanol-induced error on a circular maze test.
_Chronically, dizocilpine (0.075 and 0.15 mg/kg) prevented the development of tolerance to the effect of EtOH on error score, even though the lower dose of dizocilpine permitted tolerance to the effects of EtOH on running. These results suggest that NMDA receptor antagonists selectively inhibit tolerance to cognitive effects of ethanol even when the antagonists do not affect motor performance._

(PMID: 8545482) D-cycloserine enhances rapid tolerance to ethanol motor incoordination
_The enhancement of ethanol tolerance by D-cycloserine and the antagonism of this effect by ketamine cannot be attributed to changes in pharmacokinetics of ethanol. Taken together, these results confirm the participation of the NMDA receptor system in the development of tolerance to ethanol, and reinforce earlier findings about the involvement of learning in tolerance._

(PMID: 7938132) Effect of NMDA antagonists on rapid and chronic tolerance to ethanol: importance of intoxicated practice
_Therefore, daily administration of the NMDA antagonists was necessary to block development of chronic tolerance. Daily injection of (+)MK-801 (0.25 mg/kg IP) failed to block chronic tolerance, but inclusion of a second dose of (+)MK-801 daily, and progressive increase of this second dose during the chronic treatment period did block chronic tolerance. Unlike (+)MK-801, ketamine does not have motor-impairing effects of its own, and does not potentiate those of ethanol; it was, therefore, used in the remaining experiments. _

(PMID: 7953754) Interaction between N-methyl-D-aspartate (NMDA) and serotonin (5-HT) on ethanol tolerance
_Earlier work from this laboratory had shown that 5-HT is involved in the development of tolerance to ethanol, and that enhancement of 5-HT levels by L-tryptophan accelerated tolerance development. To explore the possibility that NMDA receptors are involved in the 5-HT effect on tolerance, we examined the effect of a noncompetitive N-methyl-D-aspartate (NMDA) antagonist [(+)MK-801] on the ability of L-tryptophan to enhance tolerance to the effect of ethanol on tilt-plane test performance by the rat. L-Tryptophan treatment resulted in the development of rapid tolerance to a dose of ethanol that failed to produce such tolerance by itself. However, prior administration of (+)MK-801 blocked the L-tryptophan effect on rapid tolerance development, in a dose-dependent manner. These results suggest that NMDA receptors are involved in the 5-HT enhancement of ethanol tolerance._

(PMID: 8415841) Effect of D-cycloserine on rapid tolerance to ethanol
_These findings are further evidence that the NMDA system, which requires activation by the glycine receptor, plays a major role in the development of at least some forms of ethanol tolerance._

(PMID: 8453972) Blockade of chronic tolerance to ethanol by the NMDA antagonist, (+)-MK-801
_Tolerance to the effects of (+)-MK-801 itself did not occur over 2 weeks of treatment. These results suggest that NMDA receptors are involved in development of chronic tolerance to ethanol as shown previously with rapid tolerance._

(PMID: 8428601) Effect of NMDA receptor antagonists on rapid tolerance to ethanol
_Results showed that (+)-MK-801 and ketamine blocked the development of rapid tolerance to ethanol on both tests. Since these drugs did not modify blood or brain alcohol levels in any of the groups, the blockade of ethanol rapid tolerance cannot be attributed to changes in pharmacokinetics of ethanol. These data suggest that the role of NMDA receptors in ethanol tolerance may be similar to their role in memory and learning, involving a facilitation of transmission in certain synapses._

*NMDAR and stimulant tolerance:* (unfortionally i found references regarding sensitisation, it is established however that NMDA antagonists upregulate several dopamine receptors backed up by many members that used it succesfull for stim tolerance).

(PMID: 2671566) Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801

(PMID: 9560846) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants

(PMID: 11915303) Alteration of neuronal activities following repeated administration of stimulants


*NMDAR and nicotine tolerance:*


(PMID: ) The NMDA antagonist dizocilpine (MK-801) attenuates tolerance to nicotine in rats
_These results suggest that the NMDA receptor may be involved in adaptation to both unconditioned and conditioned behavioural responses to nicotine._

(PMID: 18452252) The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review
_The aim of the present review is to discuss preclinical findings concerning the role of N-methyl-D-aspartate (NMDA) receptor neurotransmission in mediating the behavioral effects of nicotine, tolerance, sensitization, dependence, and withdrawal. Based on preclinical findings, it is hypothesized that NMDA receptors mediate the common adaptive processes that are involved in the development, maintenance, and expression of nicotine addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists may prove to be useful in alleviating the symptoms of nicotine abstinence and facilitate tobacco-smoking cessation._

(PMID: B8032593) Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists
_The results suggest the involvement of NMDA receptors in adaptations of the behavioural and neurochemical effects of nicotine that occur as a result of repeated administration of the drug._

*NMDA antagonists and dopamine*

(PMID: 1382178) Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat.
_D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity._

(PMID: 7770607) Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.

(PMID: 10443547) Adaptations of NMDA and dopamine D2, but not of muscarinic receptors _following 14 days administration of uncompetitive NMDA receptor antagonists.
The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%._

(PMID: 10214758) Decreased striatal dopamine-receptor binding in sporadic ALS: glutamate hyperactivity?
_In drug-naïve, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole._

(PMID: 12832726 Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
_We can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain._

(PMID: 10096038) Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
_In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP._

(PMID: 14997010) Enhanced expression of dopamine D(1) and glutamate NMDA receptors in dopamine D(4) receptor knockout mice.
_The findings suggest that D1, D4, and NMDA receptors might interact functionally and that developmental absence of D4 receptors might trigger compensatory mechanisms that enhance expression of D1 receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses._

*NMDA antagonists and serotonin*

(PMID: 9187317) Single doses of MK-801, a non-competitive antagonist of NMDA receptors, increase the number of 5-HT1A serotonin receptors in the rat brain.
I_t is concluded that single administration of MK-801 may alter the density of serotonergic 5-HT1A receptors and in consequence influence the function of the central nervous system associated with activation of 5-HT1A receptors._

*Anecdotal reports*



> I've been using Delsym (dextromethorphan polistirex, DXM, a sustained-release preparation of DXM) to prevent amphetamine-tolerance as long as I've been taking them. So that would be about 8-9 months of use without breaks, and the proof is in the pudding.
> 
> I haven't developed any tolerance whatsoever to any of the drug's effects. The dose started at 30mg/day (of the XR formulation), but an extra 30mg capsule later in the day was added onto that after a few weeks because they seemed to wear off too quickly for me. I stayed on that until a couple months ago when I switched to the immediate-release formulation, which I find lasts about eight hours per dose (quite surprisingly!), with a come-up beginning at approximately T+0:15 hours post-dose, a pronounced effect at T+1:00 pursuant, the peak at T+2:00 through T+7:00, followed by a gentle comedown which ends about T+9:00. The only difference I find between the IR and XR formulations of the drug is actually that the IR form lacks the mid-dose sluggishness and consequent "second-wind". So one dose at 6AM *really* kicks in at 8AM, beginning to wear off at 1PM; taking the second dose at noon times everything just perfectly. If I'm planning on making rounds of the bars with friends at night or practicing/playing a gig with my band, I just pop an extra 30mg in the early evening as needed.
> 
> But back to the Delsym -- I used to take a full teaspoon of the 12-hour suspension twice daily (that's equivalent to 15mg Robitussin Maximum Strength Cough every six hours). This dose completely prevented any development of tolerance and *may* have even allayed some of the nastier stim side effects by antagonizing some excitatory neurotransmission via glutamate et al. For six weeks now though I've been taking Prozac at 40mg daily, which (along with its ultra-long-half-life metabolite, norfluoxetine) is among the most potent inhibitors of cytochrome P450 IID6 (aka debrisoquine 4-hydroxylase), along with quinidine and paroxetine. CYPIID6 is responsible for the metabolism via O-demethylation (removal of the methyl group at the sixth position in the structure) of dextromethorphan, which primarily acts upon PCP2 and sigma receptors, to the potent NMDA antagonist dextrorphan (DXO; the dextroratory form of the opioid levorphan, which is about equipotent to morphine). Thus I now take twice as much Delsym to ensure a more normal ratio of DXM to DXO in the blood. My doctor and all reseach I've done has assured me that this is perfectly safe (i.e. not nearly a dose sufficient to cause Olney's lesions, etc.). I would use another NMDA antagonist like Emenda (memantine HCl) if it were available to me, even if simply to avoid the simple carbohydrates in the syrup, but Medicaid will only cover three prescriptions monthly now that I've turned 21. I may, on the other hand, finally put my lab scale to good use and order pure dextrorphan tartrate from Sigma-Aldrich (0.5 grams = $63.30) so as to avoid the unnecessary PCP2/sigma activation associated with DXM. Another chemical I'm interested in is Merck, Sharpe and Dome Inc.'s (+)-MK-801 hydrogen maleate (dizocilpine hydrogen maleate), for which the Sigma-Aldrich "Cell Signalling and Neuroscience" catalog provides the following synopsis: "Highly potent and selective non-competitive NMDA receptor antagonist that acts at the NMDA receptor-operated ion channel as an open channel blocker. Inhibits behavioral sensitization to psychostimulants and ethanol." The cost is prohibitive, though -- $43.10/5mg.





> i just wanted to follow up on the subject of DXM and amphetamines. it's been my XP that a recommended dose of cough syrup, the only active ingredient being DXM, taken with 90mg XR adderall are as follows:
> 
> -much smoother onset, more of a ramp than a rocket
> 
> -more mentally stimulating and less physically stimulating
> 
> -greatly reduced negative side effects(rapid pulse, rebound effect after dosage wears off) and condition of user less obvious to the outside world
> 
> -x-ray vision
> 
> i wish.
> 
> anyway, overall i am very pleased with the results of the combination. i plan on adding calcium and magnesium to my regimine as well.





> steady adderall xr use 30mg daily for months
> accidentally got scripted IR not XR and then had it fixed for XR but had an extra bottle of IR now
> Started using IR alternating with XR at times
> eventually started to crush XR and parachute on days I wanted them to come on stronger.
> Around this time dose started to increase to an extra 15 mg since i had the extra bottle...
> Then came getting invited to my friends djing at a club and other clubbing events
> I don't drink, smoke weed, or do any other drugs anymore, only other drug I use is clonazepam, and I WILL NOT abuse that, I've seen where benzo abuse takes you, and not going back there...that is merely something for longstanding insomnia and social anxiety (pre-existing to ADD diagnosis)
> Started popping 60 mg IR
> Started doing 60 on and off on regular days...but not all at once like on the club nights
> eventually every other weekend or every weekend id do 90mg in one sitting
> started to lose its effect...so I started blowing 60....
> I got an extra 10mg IR added to my 30mg xr script
> as finals approached, just to get basically baseline i needed 60mg, and to get focused or motivated it took 90. Ended up doing about 240 mg over two days (spread out doses)
> but I never quite as focused as I used to be. never felt high at all.
> 
> Once finals were over, I saw where this was going, decided to say **** this **** I'm not wasting my script, my mental energy, and being depending on unreasonable amounts of amphetamine just to function, not even get the therapeutic effect.
> 
> abstained from usage for 5 days completely, took tyrosine, choline, nootropics, brain supplements, etc.
> 
> Today I decided, just to see how it goes, to take 30mg, less than my full prescribed dose, along with a tablespoon of delsym and some magnesium.
> 
> Not only did I get the euphoria and motivation, but I also got the focus and energy and I DIDN'T FOR ONCE end up with freezing cold fingers!!! and its lasted much longer than using 4 times as much has and im not crashing.
> 
> Personally, I think that along with vitamins and supplements to restore neurotransmitters, taking a few day breaks between using as well as using dxm and magnesium with your dosage can change the outcome of your entire experience.
> 
> one thing i've considered...while using adderall daily, i also used nootropics....
> they counteract the nmda effects magnesium and dxm have i think..atleast the racetams.
> i didnt use any today..
> could aniracetam/other racetams possibly increase tolerance while using them?





> Small doses of Ketamine taken before a dose of dexedrine definitely did wonders to keep tolerance at bay...
> 
> But now that I'm slightly the wiser, I simply take the small doses of Ketamine, and skip the amp altogether .





> i take 30-45mg about 45 minutes to an hour before ingesting an opiate. and yes it works. i have been abusing opiates for about 2-3 months or so now and my tolerance has stayed at a pretty intermediate level. with dxm+weed 35mg of hydrocodone has me nodding pretty nicely.





> I started using DXM in conjunction with opiate use about 6-7 months ago. I always use at least 45mg, but usually 60mg of DXM with every dose of opiate. It did not reverse tolerance, but it prevented tolerance from increasing. Before I started the DXM I to slowly increase dosage every month, but once I started the DXM, and even now, my dosage has remained identical and with even slightly stronger effect from the opiate dosage than 6 months ago(so I guess some reversal may have occured).
> 
> Note: I also use a dose of 600mg of Tagament and 100mg of Diphendydramine with each opiate dose along with the DXM.





> It's an NMDA antagonist so it reduced and prevents tolerance to opiates, and for some reason it increases the warmness, analgesia, and euphoria, for me atleast. That is at therapeutic doses. Anything above 90mg's will ruin an opiate high.





> actualy you guys ;like it or not, but i am right. ever try getting dexed up and then doing a line of coke? youll get so ****ing high its rediculous.
> dxm prevents tolerance from building to ALL the drugs i listed, thats fact. but it also makes them feel stronger. opiates i notice a HUGE difference, coke i notice the BIGGEST difference, and then speed and nicotine i guess. look into it if you dont believe me im not bull****ting you
> peace


And more....



> I'd have to agree with Klowns on this one. If only from personal anecdote. Yesterday, I started taking Robitussin for an awful cough with the flu but also had to complete a lot of work. Mind you I haven't felt particularly pleasant when taking Adderal in quite some time. Anyway I had taken about 50mg's of DXM an hour prior to taking the Adderal. Then took 40 mg IR. I should also note this is about double the dose I normally take. But god damn was I flying around it felt like some of the first few times ever taking it. Also, the last dose I took was around 10 pm last night and I have yet to fall asleep or even have any sign of sleepiness. This is strange because I can often fall asleep even after taking it late at night.





> dear good people
> I SUCCESFULLY use dxm every day in small doses to prevent tolerance from building to my pain pills, and occasional pods/seeds. now let me see
> i have been on opiates around ten years, but 4-5 years of CONSISTENT every day use of hydrocodone, and dxm. now, not ONCE in these years have i EVER asked my doctor to up my dose, (rather surprising to him i believe) and i still get EXCELLETN analgesia from just 1 7.5/325 hydrocodone a dose. sure i take mroe to get high every once in a while. but i dont actualy need more. and when i go on a binge and take a bunch, and run out on thursday, i cant get my pills till monday..............well when monday rolls around, i take ONE pill, smoke weed 15 minutes later and i am still STRAIGHT ****ED UP NODDING no joke. and no i am not a lightweight, i just dont like to run out of meds and be in withdrawal. idealy, 150-300 mg would be my choice of dose for the whole day, but alas, i cant get anyone to ****ign script me that much.
> i take anywhere from 30-120 mg dxm in the morning. i find polystyrex works better than bromide, it lasts all day, and it wont cause a sharp spike in psychoactive effects. (i wouldnt feel them anyways i use to drink 4 bottles of tussin a day for about 6 years and i had to go to serious rehab for that addiction). i havent fried out on it in almost exactly oen year. this drug IS a miracale drug, and no i wouldnt call it toxic to the brain. i would say it HELPS THE BRAIN, i mean, it is basicaly useful in EVERY sort of addiction, not just opiates, it can prevent tolerance to ALL kinds of drugs like caffeine nicotine amps, i mean ALL MANNER of drugs.
> all the people i know who heavily abused dissociatives are now off them and are some of the most intelligent people i know.
> olneys is OUT THE ****ING WINDOW come one now people. if wedMD calls DXM a "Co-Analgesic", well **** thats good enough for me. it also greatly reduces fybromyalgia pain even by itself, and if i take grapefruit juice first then a small dose of dex when i have NO pain meds, it actualy gives me SIGNIFICANT wd relief AND pain relief.
> look more into these drugs before you bash them anyone, please, because i believe them to be miracle drugs.
> and ketamine, is the safest of the dissociateves anyways, just for your information. even when all that olneys **** was going around, they said PCP was most likely to cause it, followed by dxm, followeed by ketamine. i have also have ++++ psy experiences on K.
> show me any real evidence that the **** is hard on the brain any ill listen. but even if it is miniscualy bad for you............its either that, or a never ending skyrocketing opiate tolerance.............hummmm.....hard descision
> peace





> I'm also inferring from the study that the researchers must consider DXM safe taken long-term. I mean, assuming 80mg morphine qid, we're talking 320mg of DXM daily -- still quite a bit shy of the gram recommended above, but 320mg is (for most people) a very psychoactive dose. I'm only taking 15mg and definitely feel it helps. I can't explain my lack of Ultram tolerance after 400mg/day for several months any other way.





> Well, I'm hanging on 40mg of Adderall with 3 NDMA antagonists: L-Theanine at 100-200mgs, DXM 60mg. Magnesium up to 1000mg. I first used 10 mg Adderall but without NDMA antagonists in two months had to jump up to 40 mgs. Then I started using the above and I can say that (I think) they work. I'd use acamprosate or memantine if i'd have access though.





> Hiya,
> 
> I wasn't able to look through all these studies to see if they gave any definitive information on human dosages of DXM which block NMDA receptors, but 60mg Delsym seems to work great for me -- there's no way in hell I'd still be finding relief from 60mg Adderall if it weren't for the DXM!





> Vince,
> 
> Memantine, for me at least, is effective for amphetamine tolerance. Whereas before it would poop out ofter about 3 days, leaving me wrung out and irritable, it now gives me a smooth effect (one dosage of 40mg. lasts about 12hours), that I can take every day- giving me energy, concentration, motivation and social confidence.
> 
> I've waited to log this post because I was hoping to learn exactly what mechanisms allowed memantine to work this way. But, at this point, at least, I will have to say that it is a bit of a mystery. Presumable, amphetamine induces hyperglutaminergic activity, which incuces the tolerance, which the memantne is able to prevent by limiting glutaminergic activity to within physiologically safe bounds.
> 
> Also memantine is seemingly effective for tardive dyskinsia (see patent referred to above). Also effective as a adjunct mood stabilizer to valporate acid (sp?) and possibly lamotrigine.
> It is speculated to be effective for OCD disorders. Also I can't help but wonder if it won't prevent , at least in some , instances, of AD poop out.
> 
> BTW: I take, 5mg/day selegiline, 40mg/day adderall, 30mg./day memantine, 4g.day klonopin at night and 50mg./day of amisulpride.
> 
> AndrewB





> It's hardly utopia, but memantine to attenuate amphetamine tolerance to mood/motivational effects has worked for me (at 9 weeks in), and among a few others, this guy who documented his experiences with some extensiveness:
> 
> Like andrew I in the past acquired complete tolerance to the mood/motivational effects of amphetamine after about 2 or 3 days of chronic dosing, leaving a concentrative effect which for me (not everyone) always felt zombifying. These mood/motivational effects (in combination with the concentrative effect) are considerably more therapeutic for me.





> > I'm not concerned with development of tolerance as I've been able to maintain a constant effect from amphetamines for months now without raising dose. In all fairness, I do take 60mg Delsym (dextromethorphan polystirex) twice daily, which is quite likely preventing tolerance. My pdoc endorses the use of DXM to all his stimulant-treated patients now, ever since I brought it to his attention months ago. He's seeing many patients finally stabilized on doses of amphetamines whereas they used to escalate monthly or even weekly. It doesn't seem to be working as well for his patients taking methylphenidate.





> I take (d)-amphetamine 15mg IR ~3 days per week. It works very well for SA and sometimes can make me very extroverted, but it's not a practical treatment as tolerance sets in if I use it more frequently.
> 
> After hearing many glowing reports about how memantine inhibits the development of amphetamine tolerance, I started taking it at 5mg for 4 days, and have been on 10mg/day since. On the 12th day of being on 10mg memantine, I took my usual 15mg dose of amph, and felt a powerful surge of euphoria, sociability, confidence, and was completely free of SA. It was just like taking amphetamine for the first time! Over the next 4 days, I took 15mg each morning but skipped one day. Each dose was just as powerful and efficacious, AND the duration was extended to ~7-8 hours! So this brings me to today, where I decided to reduce my amph dose to 10mg, and it's working even better than 15mg did before starting memantine.
> 
> Could memantine render amphetamine a practical longterm treatment for SA/social anhedonia (among many other disorders)? Looks like it may, but I'll have to give it the test of time. Anyone else have any experience with this regimen?





> Memantine has truly saved my life, i do not exaggerate. Although Memantine, by itself, doesn't offer me significant benefits (other than reduction of OCD) it pretty much, is the most important part of my regimen. It doesnt seem possible to actually prevent the tolerance to the Actual beneficial effects of Amphetamine, but....it is possible. I see no benefit in taking Amphetamine at all, if not combined with Memantine. I currently take 15 mg Memantine a day......5 and 10mg/day both significantly inhibited tolerance, however, only for a period of 2-4 weeks, I could take Amphetamine consistently (every day, 30mg) with its mood-elevating and anxiety-reducing and pro-social benefits, continuing to remain and be of use. When tolerance becomes a problem, i take short 2-5 day breaks from Amphetamine, and every time, my tolerance goes down significantly, and I am able to resume amphetamine, with its beneficial effects being much stronger again.
> 
> There is ALOT of evidence, that Memantine and other NMDA antagonists/glutamate antagonists reduce some of the neurotoxicity of Amphetamine. Some of the neurotoxicity will remain, regardless of NMDA antagonism.....however, glutamate itself, is responsible for a significant portion of amphetamine-induced neurotoxicity......honestly, Memantine appears to be, almost perfect, without any obvious shortcomings. It will only be a matter of time, before a negative effect of such, is discovered, but nevertheless, Its positive effects, appear to greatly outweigh its cost. Yay for memantine





> Memantine is good stuff. I've been taking 5mg a day for several weeks now, and i'm just now starting to see its tolerance prevention ability. I took one 20mg adderall XR + 5mg memantine this morning after a 4 day break from adderall and it has worked great all day. I lost the magic there for awhile but today the addy is working like it did during the first few months and this is just from 20mg.


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## Mr Blonde

Good work collating everything brother, interesting reading there.


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## monstanoodle

Couple more anecdotal bits from myself:


			
				monstanoodle said:
			
		

> DexterMeth said:
> 
> 
> 
> 
> 
> 
> 
> monstanoodle said:
> 
> 
> 
> 
> I've heard many-a-time about NMDA Antagonists acting to diminish tolerance to Opiates and, I'm in no way certain that it's a complete fact, but one week I was using both H(eroin) and K(etamine) together - smoking the prior, snorting the latter.
> I did notice that after a week of heavy use of both that, when I had run out of H, used K for a few more days (which helped massively with any withdrawals I experienced) until I scored some more H, my tolerance to H was practically the same as it was at the beginning of the week if not reduced slightly.
> 
> Now, I'm not claiming it to be a solution to tolerance, and I could even be mistaken, but it definitely seemed to have the effect of keeping tolerance at a constant level and then, when only using K for a couple of days, had slightly diminished my Opiate tolerance.
> 
> Anyway, it may be something you (dear reader) might wish to try out and report back. Just thought I'd add my tuppence
> 
> 
> 
> But you stopped doing H in the first place for a few days before starting again. How does this prove anything other than taking a break from opiates for enough time to get the shit out of your body will lower your tolerance?
> 
> Click to expand...
> 
> 
> After a few days my tolerance would have definitely remained the same (from past experience) and my tolerance, after using K simultaneously, was the same as it was at the beginning of the week of using both H & K.
Click to expand...


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## MeDieViL

Interesting thx for posting your experience, altough i have to say that its possible that ketamine isnt as effective as the other nmda antagonists due to its short half life, when it wears off there could also be a small rebound wich would be counterproductive. But it did seem to help you.

Also a couple of extra notes:
- Memantine is probably the best agent for tolerance to therapeutic doses of amp/opiates etc, but maybe not to recreational doses of a combination of several agents, this is because it has a VERY low affinity for the NMDA receptors, this way it can even be considered a cognitive enhancing drug as it doesnt interfere with normal cognition in most cases. However this also means that it can be easily overpowered if taking too high doses or combo's of several drugs.

When going on a drug binge it would be better to use more powerfull NMDA antagonists like DXM (or augment memantine with some DXM).

- When using DXM go for the extended release version to make sure it doesnt wear off too soon.


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## monstanoodle

MeDieViL said:


> Interesting thx for posting your experience, altough i have to say that its possible that ketamine isnt as effective as the other nmda antagonists due to its short half life, when it wears off there could also be a small rebound wich would be counterproductive. But it did seem to help you.



Yes I can imagine that it's not the best NMDA Antagonist, but I think I know the reason as to why it may have worked so well...

Basically I'm not one of those people who likes to snort half a G and fall into that strange ol' K-hole, I prefer to take small lines continuously.
So, eventually I will meet the K-hole, but I build up to it slowly - little line by little line by little line.

This will have kept the blood concentration more constant no doubt 

The Memantine does sound really good and would likely be perfect for the job


----------



## Shambles

You missed the most obvious one of all - NMDA antagonists effect on the tolerance of NMDA antagonists - has to be the most ridiculous of any drug. Someone came round with a bit of ket last night - been a bit of a drought on so had none for many months - tolerance has barely dropped in all that time. On the plus side, maybe it's kept my tolerance to other stuff down to more managing levels too :D


----------



## MeDieViL

Shambles said:


> You missed the most obvious one of all - NMDA antagonists effect on the tolerance of NMDA antagonists - has to be the most ridiculous of any drug. Someone came round with a bit of ket last night - been a bit of a drought on so had none for many months - tolerance has barely dropped in all that time. On the plus side, maybe it's kept my tolerance to other stuff down to more managing levels too :D



Yes, ket tolerance is something unsolvable at this point, a drug i luckily never build a tolerance too but ive had so little oppertunities to try it.


----------



## MeDieViL

Post has been updated, if anyone has more ref's regarding the interaction between NMDA and other receptors, please post them.


----------



## fryingsquirrel

At the request of the OP, here's my purely ancedotal experience, the pharmacology is largely over my head. Having read that the use of DXM (among other which I do not have easy access to) could prevent tolerance to amphetamines I decided to give it a try. I had spent about a week with my anti-drug family, so I had used no drugs except a few benzos and a little pot. So my amphetamine tolerance was pretty low by my standards, though probably still off the charts compared to most people. I had easy access to but high quality ice and to anny meth [snip]. Obviously I can't give specific numbers for the purity of either, and I wasn't weighing my dose. I would just throw a large amount in a spoon and put an amount of water on it which was not sufficient to dissolve all the meth. I would then draw up a shot of what I assume to be the maximum amount of meth which will dissolve in that amount of water. If anyone knows how much meth say a CC of water will dissolve I'd be curious to know. Anyway, I would draw up 30 units per shot. This was a very strong dose, even with my tolerance. I was taking 60 mgs of DXM in the form of 4 15 mg robotussin cough gels twice a day, though I'm sure I missed a few doses given how spun I was. I would do a shot about every six hours, although I wasn't timing them or anything. This continued for what I later realized was 12 days. I neither upped my dose nor increased the number of doses per day. I've stay up this long on more occasions than I care to admit, and I would typically be up to around 50 units every 4 hours or so. Yes, I realize how insane these doses must seem. But even at the end (when my wife told me it was time to get some sleep) I had noticed no increase in tolerance. Also I had no paranoia at all, not even the level which would have been rational for someone in my position. I haven't had a chance to try this again, my lifestyle has changed to the point that more than a weeekend warrior type tweeking isn't an option. But I know myself well enough to know that I will go on another crazy meth run again, and when I do I absolutely will be repeating the DXM dosing, both for the sake of science and to get higher off my dope.

This being a harm reduction site I feel obliged to say "Don't try this at home, these stunts are performed by experienced tweekers".


----------



## Jabberwocky

^just be a little more cautious posting such things in the future.  law enforcement check these boards remember?


----------



## adder

Well, articles are articles, research is research... But to be honest I've never experienced a substantial decrease in opioid tolerance if any at all in my life. I've never been an every day consumer of any NMDA antagonist, I really did such things occasionally but it didn't really have any impact on my intake of opioids (well, unless I shot morphine and ketamine together - well, but I'd rather say it was kind of synergy between two drugs and not any decrease in tolerance).


----------



## MeDieViL

adder said:


> Well, articles are articles, research is research... But to be honest I've never experienced a substantial decrease in opioid tolerance if any at all in my life. I've never been an every day consumer of any NMDA antagonist, I really did such things occasionally but it didn't really have any impact on my intake of opioids (well, unless I shot morphine and ketamine together - well, but I'd rather say it was kind of synergy between two drugs and not any decrease in tolerance).



Well thats kinda expected since NMDA antagonists wont reverse tolerance, they rather slow the development of tolerance, also you need to chronically dose them while you are taking the other drugs.

DXM and memantine appear to work and we have good indications on what doses are effective, ketamine on the other hand has a very short half life wich could render it useless for this purpose, unless you really try to redose in time and do it chronically but thats rather impractical with ket.


----------



## MeDieViL

Can anyone move my thread to the advanced section?

Thx


----------



## Captain.Heroin

MeDieViL said:


> Can anyone move my thread to the advanced section?
> 
> Thx



I'll talk it over with the other Other Drugs moderators and see if they are on board with the idea.  I don't see any problem with doing so though.  

I have always been impressed with your thread here, though I haven't had any practical purposes for it.  



MeDieViL said:


> Post has been updated, if anyone has more ref's regarding the interaction between NMDA and other receptors, please post them.



I have combined ketamine once with mushrooms (peak of the trip), and once with LSD (tail end of the trip).  Both times I IV'd it.  By far the effects lasted much longer than they otherwise would have (IV Ketamine by itself doesn't last long, but with the mushrooms, it lasted hours, seemingly much longer).  During the tail end of the LSD trip, the duration was only 2-3x longer, but it was really, really intense, and definitely brought back a lot of the visual/tactile sensations that were waning.  

I was definitely impressed with both experiences and wasn't experiencing the high degree of synergy that I did.


----------



## MeDieViL

The reason i wanted it in advanced is because i can get some more scientific discussions going, the thread is dropping to the back all the time anyway, perhaps its a better idea to make a link to my thread in one of the informative sticky's on here with general info about drug use.

Cheers,

I also have experimented with MDMA the last 2 weeks and memantine helps a ton with the comedown, basicly no week aftereffects, just a bit skecthed out the day after.


----------



## MagickalKat777

I wonder how NMDA antagonism would affect benzo withdrawal... Its largely speculated that the vast majority of benzo withdrawals are mediated through NMDA getting out of control... I've heard of people K-holing themselves for literally days at a time and making it through benzo withdrawal...

Unfortunately, getting ahold of memantine is proving difficult recently - I've been trying unsuccessfully for about a month now - because I would like to get off my benzos and anything that will help... but I'm not gonna shove myself in a permanent K-hole for a week.


----------



## MeDieViL

MagickalKat777 said:


> I wonder how NMDA antonism would affect benzo withdrawal... Its largely speculated that the vast majority of benzo withdrawals are mediated through NMDA getting out of control... I've heard of people K-holing themselves for literally days at a time and making it through benzo withdrawal...



Well, i good friend of me reversed allmost all the tolerance he had to xanax (took it for years) however that only happened when he went to 40mg of memantine, after that he added in topiramate and did a fast withdrawal (topiramate also blocks one of the pathways involved in withdrawal.


----------



## MagickalKat777

Interesting... I'm on 40mg of valium a day and looking to get off as soon as possible - or at least knock the tolerance down to a point where I can taper much quicker...

It seems that NMDA antagonism is the way to go... but getting the memantine is the problem. (I edited that initial post).

And really, adding dope-a-max? Ugh.


----------



## MeDieViL

Here is he's experience:


> I took Alprazolam for 3 years, then went through accidental cold-turkey withdrawal because the local pharmacies weren't carrying any (happens where I live occasionally, sucky country/city). I experienced severe withdrawal symptoms including paranoia and transient psychosis but soon I got again on Alprazolam and thankfully didn't have a seizure. During that period I was completely tolerant to 2 mg Alprazolam's both sedative and anxiolytic effects.
> 
> Since I started taking Memantine, the tolerance was reversed somewhat and 1 mg was anxiolytic and practical enough for social anxiety disorder. 2 mg was very effective sedative. Tolerance didn't develop any further from this point on.
> 
> When I began tapering off Alprazolam for good, I was on 2 mg/day and the withdrawal was pretty negligible, only symptoms were irritability and slight sense of panicking, despite the rapid taper process.


I remember him saying on MSN he added in topiramate to make the last taper easier wich worked succefully, the was off them quite quikcly.


----------



## MeDieViL

Captain.Heroin said:


> I'll talk it over with the other Other Drugs moderators and see if they are on board with the idea.  I don't see any problem with doing so though.
> 
> I have always been impressed with your thread here, though I haven't had any practical purposes for it.
> 
> 
> 
> I have combined ketamine once with mushrooms (peak of the trip), and once with LSD (tail end of the trip).  Both times I IV'd it.  By far the effects lasted much longer than they otherwise would have (IV Ketamine by itself doesn't last long, but with the mushrooms, it lasted hours, seemingly much longer).  During the tail end of the LSD trip, the duration was only 2-3x longer, but it was really, really intense, and definitely brought back a lot of the visual/tactile sensations that were waning.
> 
> I was definitely impressed with both experiences and wasn't experiencing the high degree of synergy that I did.



I'm still trying to figure out how they modulate the serotonine symptons, they appear to upregulate 5HT1A rapidly but no idea about the other receptors.


----------



## MeDieViL

Bump! I would like to get a few things discussed in the advanced section


----------



## MagickalKat777

I've got 240 pills of "Namenda" (memantine) on the way... going to start with 10mg for 2 days to see how the brain fog is, then bump it to 20mg for a week - I have a feeling that is all that I'm going to need. Then when my valium suddenly knocks me on my ass I'm going to drop the dose by 10mg and see how I feel... if I'm still getting knocked out after a few days, I'm going to drop it again - by 5mg this time... even a 15mg cut in 2 weeks would make me supremely happy.

I can do DXM too - it seems like people are using 60mg of Delsym? Would this be favorable as well? Or just do ONE NMDA antagonist? lol. I really want off of these fucking benzos!


----------



## MeDieViL

Well my mate only noticed a reversal of benzo tolerance after he went up to 30-40mg of memantine, you can augment mem with some DXM to get the same results of a lower dose.


----------



## MagickalKat777

Well I started Delsym today. 30mg every 12 hours I imagine?


----------



## MagickalKat777

Updating. I ended up taking 60mg Delsym at 2PM yesterday, 60mg at 4:30AM or so this morning.

I ended up passing out some time around midnight and didn't take my valium. Upon waking at 4:30 I would normally be in mild withdrawal (half-life means nothing with my body - my metabolism is ridiculously fast) but I actually wasn't and I didn't take any valium until about 30 minutes ago when I took 10mg instead of my usual 20mg.

My morning cigarette really hit me hard too. Like I smoked half of it and when I went back in the house, I was quite dizzy and had a huge nicotine rush but ironically I didn't have my heart rate start pounding like it normally would if I had such a rush.

The NMDA antagonism is already starting to work its magic. The valium is kicking in faster and I've actually got some euphoria creeping in from it and its making me tired. This is astonishing - I've never gotten euphoria from any benzo except Xanax before - and I only got that when I first started to take it. The valium at half the dose is making me want to take a nap - and I just woke up - there really is a lot more than placebo to this!


----------



## MeDieViL

Awesome news, indeed NMDA antagonists are very promosing for drug tolerance, please keep the updates coming!


----------



## Captain.Heroin

Moved to Advanced Drug Discussion due to request from the OP.


----------



## seep

thanks Magicalkat for the polistyrex dosing suggestion. I'll try this myself with my 2 physical dependencies: alprazolam and amphetamine

any data on how chronic DXM affects testosterone production?


----------



## MagickalKat777

seep said:


> thanks Magicalkat for the polistyrex dosing suggestion. I'll try this myself with my 2 physical dependencies: alprazolam and amphetamine
> 
> any data on how chronic DXM affects testosterone production?



I don't know about actual scientific studies but I used this stuff daily in 2nd and 3rd, sometimes 4th plateau doses for over a year (I was quite addicted) and never had any issues with testosterone levels during the 2 physicals that I had.

The doses for NMDA antagonism are obviously much lower than those required for recreation so I wouldn't be terribly concerned about it.

I ended up taking yet another nap today. I'm going to stay on the 30mg of Valium for a week though and see how I feel. It definitely looks like Delsym will help me get my tolerance down, if not kick the benzos entirely.

The interesting thing is that NMDA antagonists prevent seizures as well so even if I start having nasty withdrawals (which I'm highly doubting at this point), I don't have to worry about having seizures.

Once I've been on the 60mg twice a day for a week or so I'm going to knock it down to 45mg twice a day and see how that goes. I've heard that 60-80mg a day should be plenty sufficient for NMDA antagonism but would rather start off high and move down slowly, especially given the large safety profile of DXM.

The big key thing for me is going to be staying sober during this period - that's easier said than done when you have penis envy mushrooms lying about as well as moon rocks, MDA, and research chemicals... But in order for this to work, I'm going to have to abstain (plus I don't want to tempt the serotonin syndrome gods - even with such a low dose of DXM I would rather not risk it).


----------



## soccerfocus05

i've obtained memantine overseas, [NOT ASKING FOR SOURCE], do you have an rx or obtai them domestically (assuming you are usa)


----------



## seep

seep said:


> . . . polistyrex . . . I'll try this myself with . . . amphetamine



This shit is the shit!


----------



## seep

original post said:
			
		

> (PMID: 2671566) Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801



um, the locomotor, stereotypical and convulsant effects are reversed but not the euphoric effects? That is sorta what I'm experiencing (to varying degrees)


----------



## Tomer

Thanks for the posts, everyone.

I just purchased some Delsym today (12 hour Extended).  I took a 5ML dose about 5 min. ago and plan on dosing my Dex in about 45.  Is 5ML once or twice a day sufficient, or, would it be advised to take a larger dose?  Please advise.

Cheers


----------



## Cloudy

Last winter I consumed a few grams of K over about 2-3 week period.  At the same time I was taking tramadol practically everyday, or every other day for 3 weeks.  During that period I did have to increase the dosage a little bit, but I never felt like i had to go over 500mg (I would have a benzo on hand or have consumed a light dose before taking the tramadol) during that whole period.  I started dosing 200mg from the get go, but probably could have hit 300mg at the time to get a decent nod.  What was most noticeable about the experience was the lack of any sort of physical or mental reaction from stopping the tramadol use.


----------



## MeDieViL

seep said:


> um, the locomotor, stereotypical and convulsant effects are reversed but not the euphoric effects? That is sorta what I'm experiencing (to varying degrees)



Reverse tolerance is sensitization, the first time you take a substance tolerance occurs normally, however after stopping the substance a few days sensitization kicks in causing craving and also increased sensivity to the drug mediated by a CREB related mechanism (if i remember correctly something like dopamine in the nulceus accumbens --> NMDA --> CREB), after witch tolerance occurs normally again, but with craving "implanted" in the brain, not really related to normal tolerance we experience, i didnt find any references regarding tolerance itself to amphetamine (except one to cocaine) however many anecdotal reports confirm it works for amp tolerance.

Personally i noticed that 20mg of memantine does very little for tolerance, 40mg works great with 60mg being optimal (in my case, high dose tough and may cause bad brainfog for some, that dose also isnt actively used so be aware of that).

In case of memantine you need to take a break before reversal to the euphoric effects occurs and then readd amphetamine or it isnt capable of reversing tolerance, i would assume its the same with DXM, anecdotally it appears that NMDA antagonists make the withdrawal a ton easier, making it much easier to take a break.


----------



## MeDieViL

I'm gonna switch to DXM tomorrow myself untill i got memantine again, my dex pooped out within a few days.


----------



## seep

Medievel either I'm severely dyslexic or that study says that MK-801 _blocked_ sensitization (or caused "desensitization" if there is such a thing).


----------



## MeDieViL

seep said:


> Medievel either I'm severely dyslexic or that study says that MK-801 _blocked_ sensitization (or caused "desensitization" if there is such a thing).



Yes i know thats what i ment, sensitization occurs before tolerance occurs but its not really relevant, the fact they block sensitization doesnt mean they wont work against tolerance to the the euphoric effects.

Read this for more information behind the dynamics of sensitization, tolerance and addiction:
http://www.mesolimbic.com/article/addiction.html
http://www.nature.com/embor/journal/v7/n2/full/7400635.html
http://neuro.psychiatryonline.org/cgi/content/full/20/1/23


----------



## seep

Prof. Dr. K. Kuschinsky said:
			
		

> After repeated administration of psychostimulant drugs, a sensitization rather than a tolerance to the behavioral effects can be observed.



Oh.


----------



## MeDieViL

seep said:


> Oh.



That doesnt really occur in humans tough, there's definatly tolerance going on rather then sensitisation, i beleive it may have to do with the dosing regime in rodents or differences btw humans and rodents, i'm not sure about it.


----------



## MeDieViL

Both seep and someone else (pmed me forgot username) have noticed that adding DXM to amp reverses tolerance to the locomotor and stimulating effects but not the euphoric effects, therefor i think a break is essential to reverse tolerance in the reward pathways, after wich DXM can be readded.


----------



## MagickalKat777

Be careful using DXM... it has nasty interactions with a lot of things. I stopped using Delsym after a bad reaction with 4-HO-MET and my 60mg twice a day DXM dose (was mild serotonin syndrome type effects).

I just received my memantine and reading the literature that came with it:

"Memantine showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors and for voltage dependent Ca2+, Na+, or K+ channels. Memantine also showed antagonistic effects at the 5HT3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency."

I find it fascinating that it antagonizes 5HT3 - this is the receptor thought to be associated with vomiting and is what odansetron (Zofran) and other -setron drugs do. As many will know, these drugs are quite powerful anti-emetics. This makes me hopeful that memantine will prevent nausea and vomiting from certain substances.

The nicotinic acetylcholine receptor blockage explains why smokers tend to quit on memantine - nicotine specifically activates that receptor.

Further, the paperwork also says that it has 100% bioavailability and peak concentrations hit after 3 to 7 hours and the elimination half-life for the drug is 60-80 hours, with most of the drug (57-82%) being excreted unchanged. Also, CYP450 is not involved, unlike DXM.

Also, "the mode of action suggests that the effects of L-Dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with memantine. The effects of barbituates and neuroleptics may be reduced."

That explains part of the reduction of tolerance.

It also notes that the concomittant use of other NMDA antagonists (specifically mentioning amantadine, ketamine, and DXM) has not been evaluated and their use should be with caution due to the risk of pharmacotoxic psychosis.

The side effects seem rather minimal and no higher than placebo and they even speak of a 400mg overdose that "the patient experienced restlessness, psychosis, visual hallucinations, somnolence, stupor, and loss of consciousness. The patient recovered without permanent sequelae."

Sounds like higher doses become more like classic dissociatives. I wouldn't do that because of the extremely long half-life, however.

I see my doctor at 3 today and I'm going to tell him of my plans to start memantine and also ask for a low-dose prescription of Topamax to block AMPA in the last stage of benzo withdrawal.


----------



## MeDieViL

ive used memantine up to 80mg a day, was pretty much side effect free, its very easy to tolerate, it does potentiate several things such as dopaminergics. From what ive read it doesnt appear to be as strong as DXM for the reductionof tolerance while DXM is capable of reversing tolerance, mem seems to only dramatically slow it down. Its a very good med.

It also caused a huge difference in the MDMA comedowns, so i beleive it may also work for MDMA tolerance.

I highly recommend memantine instead of DXM.


----------



## MagickalKat777

DXM's activity profile is too broad-spectrum even if it reverses tolerance... and mem seems perfectly capable of reversing tolerance as well, just using higher doses or possibly just needing to take a longer break from the substance you're tolerant to.

I'm curious to see if memantine drops cathinone tolerance though - my cathinone tolerance is so high right now that I took 600mg of methylone and 400mg of M1 the other night and barely felt a thing until I took 2C-D, then I was rolling my ass off.


----------



## MeDieViL

MeDieViL said:


> Yes i know thats what i ment, sensitization occurs before tolerance occurs but its not really relevant, the fact they block sensitization doesnt mean they wont work against tolerance to the the euphoric effects.
> 
> Read this for more information behind the dynamics of sensitization, tolerance and addiction:
> http://www.mesolimbic.com/article/addiction.html
> http://www.nature.com/embor/journal/v7/n2/full/7400635.html
> http://neuro.psychiatryonline.org/cgi/content/full/20/1/23



Those article mentions the major role of NMDA and CREB and addiction and tolerance, there does seem to be a CREB inhibit available namely curcumin:



> Neuroreport. 2009 Jan 7;20(1):63-8.
> Curcumin blocks chronic morphine analgesic tolerance and brain-derived neurotrophic factor upregulation.
> Matsushita Y, Ueda H.
> 
> aDivision of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
> Abstract
> This study was carried out based on the assumption that brain-derived neurotrophic factor (BDNF) may counterbalance the action of morphine in the brain. Morphine analgesic tolerance after daily administrations for six days was blocked by intracerebroventricular injection of anti-BDNF IgG on day 5, but not by administrations on days 1-4. Chronic morphine treatment significantly increased the expression of exon I and IV BDNF transcripts, indicating differential regulation of BDNF gene expression. Daily administration of the CREB-binding protein inhibitor curcumin abolished the upregulation of BDNF transcription and morphine analgesic tolerance. These results suggest that curcumin might be a promising adjuvant to reduce morphine analgesic tolerance, and that epigenetic control could be a new strategy useful for the control of this problem.



Ive experimented with curcumin for the past days (without memantine) and noticed it seemed to COMPLETELY abolish the depression of amphetamine comedowns, even after abusing it.
I havent experiment with it enough to make any conclusions regarding tolerance but my first impression seems to be very good.

I think it will be a very good add on to memantine. Be carefull tough, its a reverseble MAOA inhibitor (30%).


----------



## MeDieViL

MagickalKat777 said:


> DXM's activity profile is too broad-spectrum even if it reverses tolerance... and mem seems perfectly capable of reversing tolerance as well, just using higher doses or possibly just needing to take a longer break from the substance you're tolerant to.
> 
> I'm curious to see if memantine drops cathinone tolerance though - my cathinone tolerance is so high right now that I took 600mg of methylone and 400mg of M1 the other night and barely felt a thing until I took 2C-D, then I was rolling my ass off.



Yeah i'm curious as well, keep us updated!%)


----------



## MagickalKat777

Interesting. I have curcumin capsules that I bought as a supplement ages ago but never took.

Its MAO-A though? Hmmm...


----------



## MeDieViL

MagickalKat777 said:


> Interesting. I have curcumin capsules that I bought as a supplement ages ago but never took.
> 
> Its MAO-A though? Hmmm...



Yeah, altough i combined it with methylone without problem, its a reverseble inhibitor, tobacco smoke inhibits MAOA with 30% tough but ive got no idea how easily curcumin is displaced from the MAO enzyme.

I'm taking 500mg JARROW curcumin.

Perhaps use it with opiates/amps/benzo's first to see wheter it is of any added value for you.


----------



## MeDieViL

More refs and reports:


> Continuous or intermittent cocaine administration: effects of amantadine treatment during withdrawal.
> King GR, Joyner C, Ellinwood EH Jr.
> Department of Psychiatry, Duke University Medical Center
> 
> Research indicates that daily cocaine injections produce sensitization to, while the continuous infusion of cocaine produces tolerance to, its behavioral and neurochemical effects. The effects of the continuous infusion of cocaine are consistent with the withdrawal syndrome reported by human cocaine abusers. The present experiment examined whether amantadine administrations during withdrawal from continuous or intermittent cocaine attenuate and/or eliminate the behavioral effects produced by these administration regimens. The rats were pretreated for 14 days with either continuous or intermittent daily injections of cocaine, and were then withdrawn from the pretreatment regimen for 7 days. On days 1-5 of the withdrawal period, half the subjects received a 5.0 mg/kg IP injection of amantadine, and the other half received a 20.0 mg/kg IP injection of amantadine. On day 7 of withdrawal from the cocaine pretreatment, all rats were given a 15.0 mg/kg IP injection of cocaine. Their behavior was rated according to the modified Ellinwood and Balster (6) scale for 60 min. *The results indicated that amantadine treatment during withdrawal eliminated the tolerance normally associated with the continuous infusion of cocaine. *In contrast, in both the saline control and daily injection subjects amantadine treatment during withdrawal resulted in a slight, but statistically significant, reduction in the behavioral effects of cocaine. The present results therefore indicate that low doses of amantadine should be considered as a potential pharmacotherapy for the early stages of cocaine withdrawal. Furthermore, the present experimental procedures may represent an effective screening methodology for potential cocaine pharmacotherapies.
> 
> PMID: 8208762 [PubMed - indexed for MEDLINE]





> Yes, I can attest to the benefits of memantine in regards to amphetamine tolerance. Prior to using memantine, I attempted to minimize tolerance to Adderall with magnesium. Whilst it did yield limited success, memantine works far better for tolerance prevention; it also greatly enhances the rate of reversal to previously built tolerance if taken during a drug holiday.





> And good luck in your re-sensitisation quest, mindsync. If you find naltrexone doesn't work like it should, I can PERSONALLY attest to the effectiveness of memantine, in both PREVENTION of tolerance and RE-SENSITISATION to opies. At least to hydrocodone, anyway (but, since they all work nearly the same way, it should work with just about any).
> 
> I took them nearly every day for a whole year and a half due to chronic chest pain, along with memantine and the occasional DXM experiment, and did NOT develop even so much as the slightest bit of tolerance.
> 
> Well, with the exception of psychological tolerance due to wearing off of novelty... Drugs just aren't as "fun" when you're used to taking them every day... even if they work CONSISTENTLY with NO tolerance...





> I've been on 20mg memantine for several months now. I can attest to the benzo tolerance reduction. I can take .5mg alprazolam as-needed now and not have to fear the awful rebound anxiety the following day.



Also i would like to add that my first post may give a too positive view as some ppl DID end up getting tolerant, it seems that for optimal tolerance prevention 40mg a day is optimal, lower doses only slow it down.


----------



## MagickalKat777

MeDieViL said:


> Yeah, altough i combined it with methylone without problem, its a reverseble inhibitor, tobacco smoke inhibits MAOA with 30% tough but ive got no idea how easily curcumin is displaced from the MAO enzyme.
> 
> I'm taking 500mg JARROW curcumin.
> 
> Perhaps use it with opiates/amps/benzo's first to see wheter it is of any added value for you.



that's EXACTLY the same brand I have.

So I saw my doctor and after checking interactions, he gave me the greenlight on memantine but he doesn't want me to go any higher than 10mg a week - he sees no problem with the 40mg dose.

This is perfect since I just got a letter from my employer today informing me that they filled my position, essentially laying me off.


----------



## seep

MeDieViL said:


> Both seep and someone else (pmed me forgot username) have noticed that adding DXM to amp reverses tolerance to the locomotor and stimulating effects but not the euphoric effects



um, your sentence is a little confusing (I do appreciate that your native language is Belgian).  

DXM preserved amp's euphoric effect, yes, but it definitely did not reverse tolerance to the locomotor effects.  In fact, it calmed them a bit.

*Additionally*, it completely antagonized the stereotypical effects.  In other words, I was not repeating the same phrase over and over and over and over and over and over and over: stuff like that. Stereotypical as in Asperger's stereotypy.

It also stopped the spontaneous crying.

Additionally, I would sometimes actually forget to take doses of amp: i.e. diminished craving.

I had to take a break from the DXM because of a weird GI event that felt something like severe acid reflux (which I've never had).  The discomfort lasted for days.


----------



## MeDieViL

Ah okay, ive misread your last post in this thread.


----------



## crOOk

Oh niceness, I started reading about this very recently for two reasons: 

1) NMDA receptors are fascinating and I'd love to research them in the future.

2) I started taking amphetamine sulfate orally, am planning to keep doing so for the next decade and am worried that tolerance is going to keep increasing. Since I started taking Magnesium citrate 3 weeks ago sensitivity hasn't been changing it seems (~1g per day dissolved in water, a ridiculous amount of actual Mg considering the size of that ligand).
I was considering to switch to DXM HBr 30mg per day for a few weeks and see if tolerance can actually be decreased that way.

I hope I'll have found out more once I have time to browse through those links. 

Thank you!

Edit: Most excellent post MeDieViL, thank you very much!! I'll order some DXM right now! They only cost 2.48€ per 20caps here in Germany, that's nothing really even if it turns out I need 60mg per day! I'll still be at less than 10 Euros per month...


----------



## MeDieViL

Changes of GABA(A) receptor binding and subunit mRNA level in rat brain by infusion of subtoxic dose of MK-801.
Kim HS, Choi HS, Lee SY, Oh S.

College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Chungbuk, South Korea.
Abstract
In the present study, we have investigated the effects of prolonged inhibition of NMDA receptor by infusion of subtoxic dose of MK-801 to examine the modulation of GABA(A) receptor binding and GABA(A) receptor subunit mRNA level in rat brain. It has been reported that NMDA-selective glutamate receptor stimulation alters GABA(A) receptor pharmacology in cerebellar granule neurons in vitro by altering the levels of selective subunit. However, we have investigated the effect of NMDA antagonist, MK-801, on GABA(A) receptor binding characteristics in discrete brain regions by using autoradiographic and in situ hybridization techniques. The GABA(A) receptor bindings were analyzed by quantitative autoradiography using [3H]muscimol, [3H]flunitrazepam, and [35S]TBPS in rat brain slices. Rats were infused with MK-801 (1 pmol/10 microl per h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2 ML). The levels of [3H]muscimol binding were highly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, the [3H]flunitrazepam binding and [35S]TBPS binding were increased only in specific regions; the former level was increased in parts of the cortex, thalamus, and hippocampus, while the latter binding sites were only slightly elevated in parts of thalamus. The levels of beta2-subunit were elevated in the frontal cortex, thalamus, hippocampus, brainstem, and cerebellar granule layers while the levels of beta3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in MK-801-infused rats. The levels of alpha6- and delta-subunits, which are highly localized in the cerebellum, were increased in the cerebellar granule layer after MK-801 treatment. These results show that the prolonged suppression of NMDA receptor function by MK-801-infusion strongly elevates [3H]muscimol binding throughout the brain, increases regional [3H]flunitrazepam and [35S]TBPS binding, and alters GABA(A) receptor subunit mRNA levels in different directions. The chronic MK-801 treatment has differential effect on various GABA(A) receptor subunits, which suggests involvement of differential regulatory mechanisms in interaction of NMDA receptor with the GABA receptors.


----------



## MagickalKat777

I started the memantine today. I took it with my 20mg valium dose and passed out for the next twelve hours. It appears its already potentiating it. Also, when I went to go get food a few minutes ago, I tried smoking a cigarette and it was absolutely disgusting. It also did not elevate my heart rate or blood pressure at all. It was as if I didn't get anything from the nicotine.

Such results were not expecting from the first dose. I took another 10mg with my night dose over valium about an hour ago and I'm extremely sleepy again.

I'm thinking about tossing in DXM as well since DXM seems to reduce tolerance while you're ON the drugs and memantine requires you to stop them it appears.

I wonder how my CREB would be involved in benzodiazepine. I talked to my doctor about AMPA and he does not feel comfortable giving me topiramate because it has a large side effect profile. He does support my use of memantine though. If it gets me off the benzos and back to "normal" then he is all for it.


----------



## MeDieViL

> Psychological drug tolerance
> The reward system is partly responsible for the psychological part of drug tolerance.
> The CREB protein, a transcription factor activated by cyclic adenosine monophosphate (cAMP) immediately after a high, triggers genes that produce proteins such as dynorphin, which cuts off dopamine release and temporarily inhibits the reward circuit. In chronic drug users, a sustained activation of CREB thus forces a larger dose to be taken to reach the same effect. In addition it leaves the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for an additional "fix".[21]
> A similar mechanism, interfering also with the dopamine system, but relying on a different transcription factor, CEBPB, has also been proposed. In this case dopamine release onto the nucleus accumbens neurons would trigger the increased synthesis of substance P which, in turn, would increase the dopamine synthesis in the VTA. The effect of this positive feedback is suggested to be dampened by repeated substance abuse.[22]


I havent read the paper wiki linked too yet but it makes complete sense to me as on curcumin i simply dont get amp depression comedown anymore, my binges are usually short lived tough but normally definatly make me depressed afterwards.


----------



## MeDieViL

> Reversal of Triazolam Tolerance and Withdrawal-Induced Hyperlocomotor Activity and Anxiety by Bupropion in Mice
> Dipesh Joshi, Pattipati S. Naidu, Amanpreet Singh, Shrinivas K. Kulkarni
> 
> Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
> Address of Corresponding Author
> 
> Pharmacology 2005;75:93-97 (DOI: 10.1159/000087189)
> 
> Key Words
> 
> Triazolam
> Bupropion tolerance
> Triazolam tolerance
> Drug dependence
> Triazolam withdrawal
> Bupropion, anxiety
> Abstract
> 
> Chronic administration of triazolam (0.25 mg/kg/day, i.p.) on days 1–8 and its withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored-chamber test. Daily administration of bupropion (2 or 5 mg/kg, i.p.) prior to triazolam for 8 days prevented withdrawal-induced anxiety in mice. Triazolam withdrawal also induced a significant increase in the locomotor activity of mice indicating an anxiogenic response. Daily administration of bupropion (2 or 5 mg/kg) prior to triazolam for 8 days also prevented withdrawal-induced increased locomotor activity. In conclusion, chronic administration of bupropion (2 and 5 mg/kg) exhibited a significant protection against triazolam withdrawal-induced anxiety and hyperlocomotor activity in mice. The result suggests the protective effect of bupropion in the management of triazolam withdrawal reactions.





> Ibogaine is a hallucinogen (psychotomimetic) that some claim interrupts addiction and reduces or eliminates withdrawal syndromes, specifically in regards to opioids.[79] Its mechanism of action is unknown, but likely linked to nAchR α3ß4 antagonism.


Wellbutrin is a α3ß4 antagonist too, seems that this antagonism of this receptors has some implications in drug tolerance, DXM appears to be an antagonist at that receptor too.

AFAIK memantine only antagonizes the alpha7 nicotinic receptor and not the α3ß4, this would explain why DXM is better at reversing tolerance in some cases then DXM, atlough memantine does appear to be efficient at reversing benzo tolerance and preventing further tolerance from occuring.

There's some good data on this receptor and addiction, will post more tomorrow, time for sleep soon!


----------



## MagickalKat777

Well at the 20mg dose, memantine is causing considerable respiratory suppression - should I take that as a sign that it is making me more sensitive to my valium dosing? I think I may need to cut back to 10mg a day as the respiratory suppression is rather significant.


----------



## MeDieViL

Cant you try to lower your benzo's doses? Memantine shouldnt do that so id say its the valium.


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## MagickalKat777

Yeah I cut the valium to 30mg a day instead of 40mg and kept the memantine at 20mg. Now I just need to see how my body does with it.

The weird thing is that the DXM did not cause this side effect and its not listed on memantine's side effect list. I may just be very sensitive to this drug??


----------



## MeDieViL

Ive been following many ppl on memantine and none have reported this side effects, maybe its a side effect of the "adaptation phase" where ppl usually notice brainfog and inhibition of amphetamine, untill a few days later it passes and most are side effect free, maybe your just sensitive to the adaptation.


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## MagickalKat777

It actually seems to be rapidly diminishing my benzodiazepine tolerance as I thought. I'm definitely withdrawing a little bit from the dose adjustment but I think when I woke up last night that I didn't take 2 valium I only took one which means I only took 50% of my dose yesterday.


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## MeDieViL

Awesome! Thx for the update mate!


----------



## MagickalKat777

Think it safe to go to 30mg or should I stay on 20 for another week?


----------



## MeDieViL

Its safe to go up, may cause brainfog tough, but its safe.

I'm really curious to find out how this stuff affects mdma and psychedelics.


----------



## MagickalKat777

I'm not getting much in the way of brain fog - but at the same time, I didn't really get much brain fog from daily DXM usage either. I just want to get off the benzos ASAP and I think the quicker I get to 40mg, the quicker I will be off my benzos.

Any idea how long I have to stay on this stuff to keep GABA upregulated so I don't go into benzo withdrawal? Couple months?


----------



## MeDieViL

If tolerance reduces enough so its easy to quit them, once your off them you can stop the memantine IMO. There's no problem going to 40mg as fast as possible, i even jumped from 40 to 80mg once lol.


----------



## MagickalKat777

Think it would be safe to toss in 60mg a day of DXM instead to get quicker tolerance reversal? I'm not doing any MDXX drugs and I don't take anything other than the memantine and my valium so I am considering it. I don't think CREB inhibitors would help me with benzos (maybe amphetamines but I'm avoiding those right now) so I was thinking DXM and memantine might be a good combo.


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## MeDieViL

Yes should be safe


----------



## seep

> Also, when I went to go get food a few minutes ago, I tried smoking a cigarette and it was absolutely disgusting.



memantine is a nicotinic (nAChR) antagonist

any idea if memantine's much cheaper cousin amantadine is strong enough to elicit the desired effects?


----------



## MeDieViL

seep said:


> memantine is a nicotinic (nAChR) antagonist
> 
> any idea if memantine's much cheaper cousin amantadine is strong enough to elicit the desired effects?



It appears to work in rodents, it does have some toxiticy issues in humans wich could limit its application tolerance prevention.


----------



## MagickalKat777

memantine is actually cheaper than Delsym if you know where to look for it. I don't know about amantadine but I have read that it is quite toxic to humans so I wouldn't recommend it.

Dizocilpine is supposed to be quite effective as well but that one isn't so readily available.


----------



## seep

MagickalKat777 said:


> Dizocilpine is supposed to be quite effective as well but that one isn't so readily available.



I wouldn't recommend doing this regimen with dizocilpine. From what I've read, it's too powerful.  Up to a certain point, you do need your glutamate receptors.


----------



## MagickalKat777

Yeah memantine, DXM, and DXO seem the best candidates for this endeavor.

I wonder if SA keeps a customer list though... because they sell DXO and DXM and I would imagine that they would keep a list of customers for the DEA, even if the compound isn't scheduled after the guy in Colorado that was ordering AMT and AET in bulk from them and selling them as ecstasy tabs.

I'm not going to risk it. The memantine is just fine - it is definitely causing respiratory suppression with me though which apparently HAS been reported with drugs like it, such as amantadine. I'm hoping the effect lessens over time.


----------



## MagickalKat777

I went up to 30mg a day yesterday. I had my first psychoactive since I started the memantine on Monday last night. I drank 3 cans of miller lite beer over the course of four hours and was TRASHED! No tolerance whatsoever. Not only that but it was incredibly EUPHORIC! It felt amazing! I had mild rushes and everything! 

There was nothing negative other than the usual dehydration which caused me to awaken with a very slight headache. Normally even just one beer will give me tachycardia. There was no tachycardia with this at all. It felt incredible actually. And normally I am the kind of guy who needs to have 3 or 4 beers within an HOUR to get buzzed. I was flat out DRUNK after drinking those beers, even though I spaced them out so far apart!

I think I'm just gonna go for broke and shoot up to the 40mg mark today with memantine. I'm hoping to drop another 10mg of valium next week (which would put me at a 50% dose reduction in two weeks) but we will see how I feel. So far it is looking pretty good - I'm not having any withdrawals from the 25% dose reduction other than psychological stuff - I can get past the psychological though since the physical signs of withdrawal are not present.

Man I can't wait til the next time I roll - if my alcohol tolerance was reduced that low and alcohol actually became a euphoric and pleasant beverage, I can only imagine what wonders MDA and MDMA will hold for me now!


----------



## MagickalKat777

Went to 40mg today. I just took 131.4mg of moon rocks and I'm coming up fucking HARD! Memantine's effect on tolerance is NO JOKE! HOLY SHIT!

I love this stuff! It has a DXM-like brain fog at first but that goes away and I actually think clearer with it than without it AND it prevented any withdrawal symptoms from such an abrupt drop in dose (25% of a benzo dose is a LOT to not have any withdrawals from - previously, a 5% cut would have me in withdrawals by the third day) then you get the added benefit of drugs actually working again! I'm already rushing and I only took the moon rocks like 15 minutes ago. This is insane! I took 150mg last weekend and didn't feel hardly shit for rushes even at the peak and I'm just COMING UP!

I  memantine. Seriously. Amazing drug.


----------



## MagickalKat777

Okay so... Memantine restores the "magic" BIG TIME... I'm so fucked up right now and it feels incredible!


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## crOOk

Just started on 60mg DXM per day and I'm wondering... Won't I acquire a tolerance to the dxm eventually? My tolerance to ketamine and pcp used to be quite high even without daily use.
I'm just saying, long term use might be problematic. Naturally all of us are pretty euphoric about this right now, as it's usually the case when new treatments are discovered until side effects become more apparent. So if anyone should notice anything out of the ordinary, he should probably report it even if he himself sees no connection to the memantine/dxm.


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## MagickalKat777

Actually, I used to use 2nd and 3rd plateau doses of DXM daily for the better part of a year, crOOk, and I never got a tolerance.

Ketamine I got a tolerance to and its permanent because of how much I did my first time... I've only done it three times but because I did like 200mg my first time with it, I have to do that much every time or I don't k-hole. At least that's the way it seems.


----------



## MyDoorsAreOpen

For my internal medicine rotation, I wrote a paper on NMDA receptor antagonism in the treatment of chronic pain. It seems that these drugs are a sort of 'reset button' on neural memory; tolerance to drugs, chronic pain, and negative thought loops are all forms of reinforced neural pathways. The reinforcement comes from the neurons inserting more NMDA receptors (actually ion channels) in the cell membrane, so that they can depolarize and fire more easily. Jamming these ion channels brings the cells back to their original firing threshold.

I think the clinical use of DXM and ketamine (to say nothing of any PCP analogs!) will always be controversial, because people not ready for an all-out mystical experience (that's most people), tend to find them highly frightening in psychoactive doses. Memantine, however, is a gem -- it's highly specific to the NMDA receptor, unlike the others just mentioned. I think it has great potential for treating a number of psychiatric and psychosomatic illnesses which are a result of reinforcing the wrong neural pathways over time.

I love theanine, too. 200mg of that, and I feel like a million dollars. I'd recommend anyone with minor depression, anxiety, or anger management issues start taking it.


----------



## crOOk

MagickalKat777 said:


> Actually, I used to use 2nd and 3rd plateau doses of DXM daily for the better part of a year, crOOk, and I never got a tolerance.
> 
> Ketamine I got a tolerance to and its permanent because of how much I did my first time... I've only done it three times but because I did like 200mg my first time with it, I have to do that much every time or I don't k-hole. At least that's the way it seems.


200mg is a regular breakthrough dose for a first timer. Mine was at 250mg back then and it was no overkill (160lbs, male, dried pharmaceutical racemic K applied intranasally). 
Ketamine tolerance is weird though, the experience changes in quality even after long intervals of abstinence. I recently had a magical experience again after 3 months of ketamine abstention. From what I know ketamine tolerance (quantitative) can sky rocket to infinity. as in people doing several grams per day and be completely functional.

I'm just afraid that long term use of these nmda antagonists might lead to an even quicker developement of tolerance towards various substances. That'd really be a shame.

Come to think of it... My cannabis tolerance has been decreasing steadily throughout the years (been using for >11yrs). I use daily at ~.1g these days. 

I've noticed this process started when I started using Ketamine 6yrs ago. Several times per week at first, occasionally for the past 4yrs. Later episodes of DXM use at lower dosages (60-200mg) for the antidepressant effect. ~5years ago a 4 month pcp binge of daily use.

I've always stayed relatively sensitive to booze which I am and have been very happy about.
I've always stayed sensitive to all empathogenic drugs unlike everybody else I've come to know who's done em more than a couple of times...  I've rolled  less than 50times I'd say, it's still absolutely overwhelming each and every time! 

While psychedelics never manage to crush me anymore due to my very frequent former use, there have occured some massive changes in trip quality over the years which seemed to increase constantly along with a quantitative tolerance which rendered the whole class of substances utterly useless. Massive physical side effects, harsh comedown, hangover, the magic is gone. Since this tendency was pretty constant, NMDA antagonists seem to have brought no benefits to me in this respect. I still love DMT and Mescaline though which had never seen changes as grave as those with other psychedelics, though they still occured.

Interestingly, I seem to be extremely sensitive to SSRI's, namely citalopram which gave me some of the typical psychedelic side effects (yawning, feeling in my throat) and massive euphoria. I can already feel emotional changes at a threshold dose of ~1mg. Standard initial dose for citalopram is 10mg...

Sooo, considering I've done DXM and Ketamine fairly regularly, but not very frequently over the past few years, I could very well imagine that even this infrequent use has been having an effect on my sensitivity towards cannabis (sensitivity started increasing around the time I started using NMDA antagonists), alcohol, maybe even MDMA and also might have increased my sensitivity to ssri's compared to my (unknown) innate sensitivity.


Is it known whether the NMDA antagonists in question will only reverse tolerance and thereby increase sensitivity to the level that could be seen before the receptors had been pharmaceutically stimulated OR will it actually increase sensitivity by separate mechanisms, therefore allowing an increased sensitivity past "natural" levels?? Damn I still haven't read through those publications...


MyDoorsAreOpen said:


> For my internal medicine rotation, I wrote a paper on NMDA receptor antagonism in the treatment of chronic pain. It seems that these drugs are a sort of 'reset button' on neural memory; tolerance to drugs, chronic pain, and negative thought loops are all forms of reinforced neural pathways. The reinforcement comes from the neurons inserting more NMDA receptors (actually ion channels) in the cell membrane, so that they can depolarize and fire more easily. Jamming these ion channels brings the cells back to their original firing threshold.
> 
> I think the clinical use of DXM and ketamine (to say nothing of any PCP analogs!) will always be controversial, because people not ready for an all-out mystical experience (that's most people), tend to find them highly frightening in psychoactive doses. Memantine, however, is a gem -- it's highly specific to the NMDA receptor, unlike the others just mentioned. I think it has great potential for treating a number of psychiatric and psychosomatic illnesses which are a result of reinforcing the wrong neural pathways over time.
> 
> I love theanine, too. 200mg of that, and I feel like a million dollars. I'd recommend anyone with minor depression, anxiety, or anger management issues start taking it.


Couldn't have said it any better!! 

I'll assume you consume the theanine orally. Do you have pills, powder or just plain tea? Seems like green tea can contain up to 2500mg per 100g tea, that's about 250mg per cup.


----------



## Dr. Beat

I took Memantine for about 1.5 years while taking Suboxone to keep my tolerance down, which it did a lot. I would get on the nod some days on this combination, usually a few days after taking the Memantine.

My experience with Memantine is less is better! So I would only take it once a week, and only 5 or 10mg. And that was enough to make a big difference to my tolerance.

The side effects were very strong respirtory depression from both drugs together, so I got a lot of sleep apnea from these 2 drugs combined. To reduce the sleep apnea, I would have a cup of black tea just before bed, and no caffeine through the day so it worked maximum while sleeping.

Little to no high from cigarettes (was only an occasional casual smoker before) or alcohol, so I stopped drinking and smoking on this combination.

I also find Memantine reduces the positive effect of caffeine, and there are a few articles on Science Direct saying Glutamate is important for the caffeine high.

I think Memantine is the safest of the NMDA antagonists for human consumption after every I have read and tried.


----------



## chaos_destroy

Sorry if i missed it somewhere in this thread but is this tolerance reversal likely to be permanent? Or will it come back when the Memantine is stopped? Will doing this cause a tolerance to ketamine at recreational doses?


----------



## crOOk

chaos_destroy said:


> Sorry if i missed it somewhere in this thread but is this tolerance reversal likely to be permanent? Or will it come back when the Memantine is stopped? Will doing this cause a tolerance to ketamine at recreational doses?


The latter question seems to be of relevance for our community. :D I have no idea about cross tolerance between ketamine and the nmda antagonists mentioned in this thread to be honest, but maybe someone else can enlighten us.
Regarding the permanence. I doubt it's permanent, but the effect does seem to last way past the point of drug excretion. We have the following anecdotal evidence for that:

-Dr. Beat's report of him only taking the Memantine once per week
-The fact that the antidepressant effects of some NMDA antagonists last way past the point of the actual intoxication, 1-2wks seems to be most common
-My experience of decreased cannabis tolerance throughout the years during occasional nmda antagonist use (see my long post 3 posts further up in this thread, frequency ranging from several times per week to a month without)

IF the mechanism MyDoorsAreOpen suggested (temporarily blocked nmda receptors) is what this is all about, then I couldn't imagine the effect to be permanent though. My cannabis tolerance does seem to increase slightly after not taking any nmda antagonists for a few weeks, but it's still way below what it used to be or what it is for most other cannabis users.


----------



## MyDoorsAreOpen

^ I never said the jamming of NMDA receptors, a.k.a. ancillary Ca++/Na+/K+ pores, was temporary. There are actually a number of physiological ways these pores can get clogged, with likely varying degrees of reversibility. I'm not well read enough on this to know whether the clogged NMDA receptors ever get endocytosed (drawn into the cell for disposal, 'taken out of circulation'), or whether it's just a matter of them staying in the cell membrane and remaining damaged and nonfunctional, but the effects of even just one use of a high-affinity antagonist seem to be quite long lasting.

I wonder if it's something akin to wiping your Etch-a-sketch™ or your hard disk, or the burn-in patterns on old TVs and monitors: for most intents and purposes you clear a whole lot of new space to establish new learned patterns of neural firing. But trace elements of the old pathways remain and are detectable on close scrutiny, and can become reestablished over time more easily than brand new ones can be formed.

NMDA receptor antagonists are no magic bullet. They have to be combined with effortful lifestyle modifications to have a permanent transformative effect. But they're the next best thing to a magic bullet.


----------



## crOOk

MyDoorsAreOpen said:


> ^ I never said the jamming of NMDA receptors, a.k.a. ancillary Ca++/Na+/K+ pores, was temporary. There are actually a number of physiological ways these pores can get clogged, with likely varying degrees of reversibility. I'm not well read enough on this to know whether the clogged NMDA receptors ever get endocytosed (drawn into the cell for disposal, 'taken out of circulation'), or whether it's just a matter of them staying in the cell membrane and remaining damaged and nonfunctional, but the effects of even just one use of a high-affinity antagonist seem to be quite long lasting.
> 
> I wonder if it's something akin to wiping your Etch-a-sketch™ or your hard disk, or the burn-in patterns on old TVs and monitors: for most intents and purposes you clear a whole lot of new space to establish new learned patterns of neural firing. But trace elements of the old pathways remain and are detectable on close scrutiny, and can become reestablished over time more easily than brand new ones can be formed.
> 
> NMDA receptor antagonists are no magic bullet. They have to be combined with effortful lifestyle modifications to have a permanent transformative effect. But they're the next best thing to a magic bullet.


Thanks for clearing that up! Even with the limited biochem knowledge you possess (more than I know about the subject) you manage, in simple words, to give me a new idea of a process that's been challenging me to see through it for quite some time.

The question would be though, by establishing new behavioural patterns while on a long term nmda antagonist schedule, wouldn't those new pathways get clogged pretty quickly as well? (just a rethorical question really... :D)
And also, what happens when tolerance has been decreased to a certain degree and the nmda antagonist is withdrawn (along with the other substance of [ab]use). Will their be a rebound in tolerance to (endogenous) transmitters binding to the receptors in question?

I'll probably know soon enough. :D

I'm still very curious about that theanine thing. I was close to buying a ton of green tea today. :D


----------



## seep

MagickalKat777 said:


> Okay so... Memantine restores the "magic" BIG TIME... I'm so fucked up right now and it feels incredible!



I'm totally getting similar results from Huperazine A.  I've been taking 100 mcg twice daily for 4 days.  I wonder if anyone else can relate to this w/r/t huperazine.

In case it's of interest to you, I've cut my alprazolam consumption in half.  Not because I'm trying to give it up but because it's suddenly too potent.  FWIW I have a 6-year daily alprazolam habit.


----------



## MeDieViL

MagickalKat777 said:


> Went to 40mg today. I just took 131.4mg of moon rocks and I'm coming up fucking HARD! Memantine's effect on tolerance is NO JOKE! HOLY SHIT!
> 
> I love this stuff! It has a DXM-like brain fog at first but that goes away and I actually think clearer with it than without it AND it prevented any withdrawal symptoms from such an abrupt drop in dose (25% of a benzo dose is a LOT to not have any withdrawals from - previously, a 5% cut would have me in withdrawals by the third day) then you get the added benefit of drugs actually working again! I'm already rushing and I only took the moon rocks like 15 minutes ago. This is insane! I took 150mg last weekend and didn't feel hardly shit for rushes even at the peak and I'm just COMING UP!
> 
> I  memantine. Seriously. Amazing drug.



Hahaha, memantine is dramatically underrated, thx for posting your experience, its amazing stuff!

As for tolerance to memantine itself, this does not appear to be the case to the anti tolerance effects of NMDA antagonists, recreational effects possibly yes.


----------



## MeDieViL

seep said:


> I'm totally getting similar results from Huperazine A.  I've been taking 100 mcg twice daily for 4 days.  I wonder if anyone else can relate to this w/r/t huperazine.
> 
> In case it's of interest to you, I've cut my alprazolam consumption in half.  Not because I'm trying to give it up but because it's suddenly too potent.  FWIW I have a 6-year daily alprazolam habit.



Interesting mate, so its NMDA antagonism seems to be strong enough to counteract tolerance too, very interesting stuff!

What results are you getting on amp with huperzine?


----------



## MyDoorsAreOpen

I wasn't aware memantine had any recreational potential on its own. For most people, at least from what I've been taught, the psychoactive effects of memantine are subtle enough to be unnoticeable for most people. Most other known NMDARAs (even magnesium), do a whole lot more than just antagonize NMDA receptors, and these actions are augmented and enhanced by their NMDA receptor action. Memantine, by contrast, pretty much just hits that one receptor, with a fairly low binding affinity, meaning any one molecule doesn't stay attached to the receptor and exert its effects very long before detaching. This is a good thing for people who want only the neuroprotective effects of NMDA receptor antagonism, and don't want to deal with any other effects, mental or bodily.


----------



## MeDieViL

^^ I was more referring to NMDA antagonists in general, like with DXM, tolerance to the recreational effects can occur but all reports consistently lack reporting a tolerance to the anti tolerance effect. Indeed memantine seems to be lacking in recreational effects only causing a unpleasant experine.


----------



## seep

MeDieViL said:


> What results are you getting on amp with huperzine?



Same as with DXM: takes the edge off while preserving the euphoria.  No bruxism, no hyperkinesis, no anxiety, no obsessive thoughts or rumination.

A little less "speediness" though. Like, I'm not talking anyone's ears off or setting things on fire.


----------



## Geaux Tigers!

I am prescribed Lisdexamfetamine (Vyvanse) 70mg./day by my doctor. I have noticed that my tolerance has increased to Lisdexamafetamine.

What NMDA antagonist, besides Memantine, would be the best to use as a daily regimen to prevent tolerance buildup? I would do Memantine, but I don't have the means to procure it at this time.

I have looked into:

10ml. Delsym Extended Release daily
Chelated Magnesium 250mg daily
200 mcg. Huperzine A daily

Should I just get this? What OTC methods would you suggest to counteract my tolerance to Lisdexamfetamine?


----------



## MyDoorsAreOpen

Does anyone else yawn a lot on theanine?


----------



## MeDieViL

> Is it known whether the NMDA antagonists in question will only reverse tolerance and thereby increase sensitivity to the level that could be seen before the receptors had been pharmaceutically stimulated OR will it actually increase sensitivity by separate mechanisms, therefore allowing an increased sensitivity past "natural" levels?? Damn I still haven't read through those publications...


It seems that receptor upregulation explains the tolerance prevention induced by NMDA antagonists, an overview of the references i was able to find:


> NMDA antagonists and dopamine
> 
> (PMID: 1382178) Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat.
> D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity.
> 
> (PMID: 7770607) Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.
> 
> (PMID: 10443547) Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.
> The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%.
> 
> (PMID: 10214758) Decreased striatal dopamine-receptor binding in sporadic ALS: glutamate hyperactivity?
> In drug-naïve, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole.
> 
> (PMID: 12832726 Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
> We can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain.
> 
> (PMID: 10096038) Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.
> In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP.
> 
> (PMID: 14997010) Enhanced expression of dopamine D(1) and glutamate NMDA receptors in dopamine D(4) receptor knockout mice.
> The findings suggest that D1, D4, and NMDA receptors might interact functionally and that developmental absence of D4 receptors might trigger compensatory mechanisms that enhance expression of D1 receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses.
> 
> NMDA antagonists and serotonin
> 
> (PMID: 9187317) Single doses of MK-801, a non-competitive antagonist of NMDA receptors, increase the number of 5-HT1A serotonin receptors in the rat brain.
> It is concluded that single administration of MK-801 may alter the density of serotonergic 5-HT1A receptors and in consequence influence the function of the central nervous system associated with activation of 5-HT1A receptors.





> Changes of GABA(A) receptor binding and subunit mRNA level in rat brain by infusion of subtoxic dose of MK-801.
> Kim HS, Choi HS, Lee SY, Oh S.
> 
> College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Chungbuk, South Korea.
> Abstract
> In the present study, we have investigated the effects of prolonged inhibition of NMDA receptor by infusion of subtoxic dose of MK-801 to examine the modulation of GABA(A) receptor binding and GABA(A) receptor subunit mRNA level in rat brain. It has been reported that NMDA-selective glutamate receptor stimulation alters GABA(A) receptor pharmacology in cerebellar granule neurons in vitro by altering the levels of selective subunit. However, we have investigated the effect of NMDA antagonist, MK-801, on GABA(A) receptor binding characteristics in discrete brain regions by using autoradiographic and in situ hybridization techniques. The GABA(A) receptor bindings were analyzed by quantitative autoradiography using [3H]muscimol, [3H]flunitrazepam, and [35S]TBPS in rat brain slices. Rats were infused with MK-801 (1 pmol/10 microl per h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2 ML). The levels of [3H]muscimol binding were highly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, the [3H]flunitrazepam binding and [35S]TBPS binding were increased only in specific regions; the former level was increased in parts of the cortex, thalamus, and hippocampus, while the latter binding sites were only slightly elevated in parts of thalamus. The levels of beta2-subunit were elevated in the frontal cortex, thalamus, hippocampus, brainstem, and cerebellar granule layers while the levels of beta3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in MK-801-infused rats. The levels of alpha6- and delta-subunits, which are highly localized in the cerebellum, were increased in the cerebellar granule layer after MK-801 treatment. These results show that the prolonged suppression of NMDA receptor function by MK-801-infusion strongly elevates [3H]muscimol binding throughout the brain, increases regional [3H]flunitrazepam and [35S]TBPS binding, and alters GABA(A) receptor subunit mRNA levels in different directions. The chronic MK-801 treatment has differential effect on various GABA(A) receptor subunits, which suggests involvement of differential regulatory mechanisms in interaction of NMDA receptor with the GABA receptors.



I'm still trying to find its effect on other receptors, like the GABAB receptor or other serotonine receptors.


----------



## MeDieViL

Geaux Tigers! said:


> I am prescribed Lisdexamfetamine (Vyvanse) 70mg./day by my doctor. I have noticed that my tolerance has increased to Lisdexamafetamine.
> 
> What NMDA antagonist, besides Memantine, would be the best to use as a daily regimen to prevent tolerance buildup? I would do Memantine, but I don't have the means to procure it at this time.
> 
> I have looked into:
> 
> 10ml. Delsym Extended Release daily
> Chelated Magnesium 250mg daily
> 200 mcg. Huperzine A daily
> 
> Should I just get this? What OTC methods would you suggest to counteract my tolerance to Lisdexamfetamine?


Id say huperzine A looks like the best option, altough only seep reported succes with it, it definatly seems to be as potent as DXM looking at he's experience.


----------



## MagickalKat777

If Huperzine A can do this at 100mcg, it would make it the most potent NMDA antagonist known to man.

It fucks with acetylcholine though... Thanks but no thanks. Too many side effects.

Possible side effects include breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, itchy or swollen skin, upset stomach, diarrhea, vomiting, hyperactivity and insomnia. Most adverse events were cholinergic in nature and no serious adverse events occurred.

(from wiki)

https://secure.wikimedia.org/wikipedia/en/wiki/Huperzine_A

I think I'll be sticking with memantine. Also, memantine FEELS like a dissociative... I don't know if this is because I just rapidly flew up to 40mg in a single week or not but it definitely feels like I'm on DXM or K, I just am not having any actual hallucinogenic effects.

I don't doubt that in a high enough dose, memantine would be hallucinogenic but it probably wouldn't be very pleasant.

So as of today its officially been 8 days since I cut my Valium from 40mg to 30mg and I've been having minimal withdrawal symptoms. Mostly just in my head - there have been no physical signs of withdrawal. 

It was far too early to roll though - I did experience a lot of anxiety when I added MDA to my MDMA and then later added 2C-D and had the most intense OEVs of my life. So it does appear that NMDA antagonists also reduce tolerance to hallucinogenic phenethylamines, not just amphetamines.


----------



## Geaux Tigers!

Thanks for your insightful post about Huperzine A, MagickalKat777! You have definitely made me think twice about attempting a regimen of Huperzine A. Also, you have compounded my jealously with your access to Memantine.

However, I'm still dumbfounded as to what daily regimen of MNDA antagonist I should proceed with to reduce my Vyvanse tolerance. 

If Huperzine A is so ineffective, what about a different suggestion? I'd appreciate any response. Thanks!


----------



## Geaux Tigers!

I was doing random reading in this forum. I came across another post from July from MagikalKat777.



MagickalKat777 said:


> Delsym. 30mg every twelve hours. Not very expensive and extremely effective. Two days at 60mg every twelve hours and I shaved 25% of my benzo dose on the third day.
> 
> Its certainly more effective than memantine but I took a psychedelic and was reminded why DXM is bad so I switched to memantine.




Would the suggestion he outlined be the most effective NMDA anatgonist regimen for me? If I solely did Delsym, would it be as effective as a cocktail of drugs, including magnesium (etc.)


----------



## avcpl

MagickalKat777 said:


> Went to 40mg today. I just took 131.4mg of moon rocks and I'm coming up fucking HARD! Memantine's effect on tolerance is NO JOKE! HOLY SHIT!



Would you say that the 40mg dose of memantine  is needed for MDMA tolerance?

I ordered some and am trying to devise a schedule.

I was thinking 10mg a day for a week, up it to 20mg for a week then roll, or is that not aggressive enough?  What would your recommendation be?

I'm one of the few that has not had roll improvement with piracetam and once took so much of it, I think it actually muted my roll). My MDMA tolerance is there, but not extreme; it's just really inconsistent even with most variables being equal. And my rolls are no where near the first few times (as is the case with most people), but not remedied by long breaks or good product or increasing doses..etc. and I don't think it's just lack of novelty either...

Thanks!  Really enjoying this thread!


----------



## blessedamines

i dont know if this was already put up but 
http://journals.lww.com/behavioural...tine_reduces_morphine_antinociceptive.15.aspx

its a article about Tianeptine and antinociceptive tolerance to Morphine


----------



## /navarone/

Hey check this Japanese drug I just found while roaming on wiki:

*Indeloxazine*






_Indeloxazine (Elen, Noin) is a so-called cerebral activator used in Japan for the treatment of cerebrovascular disease. It was launched in 1988. Indeloxazine acts as a serotonin releasing agent and norepinephrine reuptake inhibitor. It also acts as an NMDA receptor antagonist. It enhances acetylcholine release through indirect activation of the 5-HT4 receptor. Indeloxazine has nootropic, neuroprotective, anticonvulsant, and antidepressant effects._

Would love to get my hands on some of that.


----------



## crOOk

/navarone/ said:


> Hey check this Japanese drug I just found while roaming on wiki:
> 
> *Indeloxazine*
> 
> 
> 
> 
> 
> 
> _Indeloxazine (Elen, Noin) is a so-called cerebral activator used in Japan for the treatment of cerebrovascular disease. It was launched in 1988. Indeloxazine acts as a serotonin releasing agent and norepinephrine reuptake inhibitor. It also acts as an NMDA receptor antagonist. It enhances acetylcholine release through indirect activation of the 5-HT4 receptor. Indeloxazine has nootropic, neuroprotective, anticonvulsant, and antidepressant effects._
> 
> Would love to get my hands on some of that.


Nice. We are gonna see countless nmda antagonists popping up in the next couple of years. :D


----------



## MeDieViL

That stuff looks like a potentially extremely effective antidepressant, in rodents treatment resistance (and humans) has been associated with the 5HT1A receptor/gene wich serotonine releasing agents bypass, sexual dysfunctioning and mood blunting due to inhibiting phasic serotonine release also wont be an issue, that combined with the NMDA antagonism makes up for a highly interesting treatment, it also leaves the option of adding other compounds to this one wich it should probably prevent tolerance for, i see some very high potential in that compound.


----------



## MagickalKat777

Geaux Tigers! said:


> Would the suggestion he outlined be the most effective NMDA anatgonist regimen for me? If I solely did Delsym, would it be as effective as a cocktail of drugs, including magnesium (etc.)



30mg twice a day of Delsym should work quite well for reducing tolerance. DXM is unique in that you don't have to STOP the drug that you're taking in order to have a drastic drop in tolerance in a short period of time. Memantine, on the other hand, takes longer to drop tolerance if you are still taking the drug.

The problem with DXM is that it has a dirty receptor affinity profile and interacts with a lot of things. If you don't take any drugs that are contraindicated (SSRIs, SRAs, MAOIs mainly) then DXM is a great choice and it is certainly faster than memantine. You just have to watch out for drugs that interact with DXM (and there are a lot of them) and avoid them when you are on the DXM regimen. Also, memantine has a rather long half-life of 60-100 hours, which means it stays in your system much longer than DXM. I am currently doing 20mg twice a day (12 hours apart) on memantine but that's only because I experience significant respiratory suppression if I don't space it out. I'm not sure if that's a side effect of the memantine, a reaction from the tolerance reduction to my valium, or a combination, but I have noted marked respiratory suppression occasionally with memantine.

Basically, Delsym is perfectly fine if a) you want the tolerance to drop FAST, even while continuing to take the drug, b) you aren't hypersensitive to it, and c) you can avoid mixing it with incompatible substances.



avcpl said:


> Would you say that the 40mg dose of memantine  is needed for MDMA tolerance?
> 
> I ordered some and am trying to devise a schedule.
> 
> I was thinking 10mg a day for a week, up it to 20mg for a week then roll, or is that not aggressive enough?  What would your recommendation be?
> 
> I'm one of the few that has not had roll improvement with piracetam and once took so much of it, I think it actually muted my roll). My MDMA tolerance is there, but not extreme; it's just really inconsistent even with most variables being equal. And my rolls are no where near the first few times (as is the case with most people), but not remedied by long breaks or good product or increasing doses..etc. and I don't think it's just lack of novelty either...
> 
> Thanks!  Really enjoying this thread!



40mg seems to be the magic number for tolerance reduction in the short term. If you take it over a long period of time, I've seen reports of as little as 10mg cutting tolerance but not until a month or longer has passed by.

The drug is rather benign. In a single week I went from 10mg to 40mg a day, it just adds more brain fog when you do this so quickly but if you can handle the brain fog then it is much more effective much quicker.

As far as rolling goes, memantine will reduce your tolerance, however, if you don't have the monoamines available to create the roll, you'll end up with a half-assed roll, just at a lower dose than you would normally need to take.

Medievil stated that he experienced no crash from MDMA while on memantine nor did he experience the CNS stimulation effects from his amphetamine - this was not the case in my experience and I both experienced significant CNS stimulation AND had a rather nasty crash but that involved MDA, MDMA, and 2C-D in a single 24 hour period so I can't say that the crash wouldn't have been worse if I wasn't on the memantine. I have a feeling that the crash would have been lessened in intensity but I have no way of knowing that for certain because I was also 5 days into a 25% benzodiazepine cut and taking the drugs obviously messed with my levels of neurochemicals massively. I ended up having to take my Valium early but I didn't have to take more Valium than I would normally need in a day so it is really hard to say what happened there.


----------



## MagickalKat777

MeDieViL said:


> That stuff looks like a potentially extremely effective antidepressant, in rodents treatment resistance (and humans) has been associated with the 5HT1A receptor/gene wich serotonine releasing agents bypass, sexual dysfunctioning and mood blunting due to inhibiting phasic serotonine release also wont be an issue, that combined with the NMDA antagonism makes up for a highly interesting treatment, it also leaves the option of adding other compounds to this one wich it should probably prevent tolerance for, i see some very high potential in that compound.



Yes but with a 2.2 hour half-life, that's a lot of pills that would be needed every day to maintain sufficient blood levels and I haven't done a lot of research as of yet but I doubt the NMDA antagonism at reasonable therapeutic doses is of clinical significance to make much difference.


----------



## MeDieViL

I would like to add my experience regarding daily use of GBL on memantine, i take around 100ml a week and after several months didnt experience any tolerance whatsoever, i did have occasional breaks of a couple weeks because i allways ran out too soon, but i definatly should have build up a tolerance by now consider i use it alot and use it every day.

Physical addiction is something ive allways avoided on GBL, because i never took it during the day in the past, even without memantine, the timefrime you take it plays a major role in physical addiction to G imo, with not taking it for sleep too being very important.

Yeah 40mg is the dose were memantine really works, anything lower and it just seems to slow tolerance quite a bit but thats all.


----------



## MagickalKat777

I just added 30mg of Delsym because I'm withdrawing pretty severely today... Not severely... its hard to put my finger on it because I have weird body feelings but no actual physical withdrawals. Just a feeling that something is "off" and yuck.

I think adding the DXM will reduce my valium tolerance faster than memantine will... I just have to be careful not to do drugs (which I shouldn't be doing when I'm tapering anyway).


----------



## MagickalKat777

Memantine + Lyrica = WIN for Valium withdrawal. I took 100mg of Lyrica last night as an experiment and I not only got euphoric and sedated from it, I ended up passing out and sleeping an entire 8 hours for the first time since I started my NMDA regimen.

I'll be dropping the DXM as it appears that the DXM actually has a higher tolerance when co-administered with memantine.


----------



## MagickalKat777

So my withdrawal is just not going fast enough at 40mg... would 50, 60mg make a bigger impact or should I switch to Delsym for NMDA antagonism instead? I noticed that Delsym made me cut my Valium the second day I was on it...


----------



## crOOk

> *Repeated Heroin Administration: A Sensitization Process*
> 
> DISCUSSION
> The ﬁrst result of this study is that intermittent administrations of the same dose of heroin induced not only an analgesic effect but also a long-lasting enhancement in pain sensitivity (hyperalgesia), as observed with the progressive emergence of a delayed decrease of the nociceptive threshold for several days. This hyperalgesia cannot be explained by an excess of nociceptive inputs induced by behavioral testing associated with heroin administration because we reported previously that long-lasting hyperalgesia is also observed in opiate-treated rats unexposed to repeated nociceptive stimuli on the day of opiate administration (Laulin et al., 1998; Ce ´le `rier et al., 2000). This phenomenon appears an actual sensitization of pronociceptive systems because both magnitude and duration of hyperalgesia increased as a function of heroin administrations. Indeed, we observed that the ﬁrst 1.25 mg/kg heroin administration induced moderate hyperalgesia for 2 d, whereas the ﬁfth injection of the same heroin dose was followed by a larger hyperalgesia for 6 d. Our study also shows that repeated 12 once-daily subcutaneous heroin injections induced a gradual lowering of the nociceptive threshold that progressively disappeared after the cessation of the heroin treatment. Thermal hyperalgesia has also been reported 48 hr after cessation of a series of 8 once-daily intrathecal injections of morphine (Mao et al., 1994).
> Our observation that the administration of a small heroin dose (0.2 or 0.3 mg/kg), which was ineffective in inducing a delayed hyperalgesia after the ﬁrst exposure in rats, triggered substantial delayed hyperalgesia after a series of intermittent or once-daily heroin administrations is in agreement with the sensitization hypothesis. Considered as a whole, these results clearly indicate that a repeated heroin administration schedule induced a sensitization to heroin-induced delayed hyperalgesia.
> 
> The second result of this study is that pain hypersensitivity progressively disappeared in heroin-treated rats after the cessation of heroin administrations, as demonstrated by the slow return of the nociceptive threshold to the pre-drug value. Interestingly, the larger the decrease of the nociceptive threshold, the larger was the delay to return to basal pain sensitivity. Two types of processes might account for this phenomenon. The ﬁrst one would be a progressive deactivation of pronociceptive systems according to a mere homeostatic process. The second one would be a sustained and prolonged activity of the pronociceptive systems progressively opposed by an active and opposite counteradaptation that is isodirectional to the ﬁrst effect of the opiate (Poulos and Cappell, 1991; Ramsay and Woods, 1997), i.e., pain inhibition by endogenous analgesic systems (Fig. 5). Although a progressive deactivation of pronociceptive systems after the cessation of heroin administrations could not be excluded totally, our results strongly suggest a critical role for the second process. This is supported by the effectiveness of naloxone in precipitating hyperalgesia in rats that had recovered their pre-drug nociceptive threshold value after stopping heroin administration. Although the effectivenes of naloxone in precipitating hyperalgesia was only slightly increased between the ﬁrst and ﬁfth heroin injections (32 and 48% decrease of the nociceptive threshold, respectively) in the intermittent heroin injection schedule, our observation that the naloxone-precipitated hyperalgesia was maintained for 2 months after a series of 12 daily heroin administrations had ended (35% decrease of the nociceptive threshold) provides evidence that compensatory mechanisms permitting maintenance of the pre-drug nociceptive threshold value were sustained for a long time. Because an opioid receptor antagonist, which was ineffective in control heroin naive rats, induced a pharmacological effect such as hyperalgesia, this means either that opioid receptors were stimulated by a compensatory increase of endogenous opioid ligands or that signaling activity of opioid receptors is enhanced.
> 
> Indeed, it has been reported that opioid agonist stimulation results in a gradual conversion of the m opioid receptor into a sensitized or constitutively active state (Wang et al., 1994; Bilsky et al., 1996) and upregulation of the cAMP pathway (Nestler, 1992). Although these three mechanisms may account for the naloxone-precipitated hyperalgesia, the unmodiﬁed analgesic effects of heroin in this model of discontinuous administration favors the hypothesis of an increase of endogenous opioid ligands.
> 
> Studies are in progress in our laboratory to identify the nature of endogenous opioids that could be involved in this adaptive process, permitting a return to basal nociceptive threshold. Taken together, these studies suggest that heroin-deprived animals were, for a very long-time, in a new biological state associated with a high-level balance between opioid-dependent analgesic systems and pronociceptive systems that mask one another (Fig. 5). This is in agreement with the compensatory response hypothesis (Wise, 1988; Schulteis and Koob, 1996; Robinson and Berridge, 2000), especially the opponent process theory (Solomon, 1980).
> 
> The third result of our study is that, unlike sensitization of heroin-induced hyperalgesia observed after repeated administration, a change in heroin-induced analgesia was never observed.
> As reported earlier (Laulin et al., 1999), we observed that both time course and AUC related to the analgesic effect of heroin were unchanged when the opiate was injected during the hyperalgesic phase induced by heroin. During the hyperalgesic period, the shift of the nociceptive threshold is actually what produced the impression of less analgesia, i.e., apparent tolerance. Moreover, this study showed that the analgesic effect of heroin was also unchanged when heroin is administered in heroin-treated animals that recovered their pre-drug nociceptive threshold value after cessation of heroin administrations, and it is in agreement with some studies showing that intermittent exposure may lead to sensitization of a drug effect, whereas continuous exposure to a drug may lead to tolerance of the same drug effect (Post, 1980).
> This could explain why controlled clinical studies report that the dose of opiates that is required in chronic pain patients to alleviate pain (intermittent exposure) may remain constant for years on end (Twycross and McQuay, 1989; Foley, 1991; Portenoy, 1996). Taken together, these data indicate that the increases of the opiate doses that are sometimes required to alleviate pain in suffering patients are caused either by disease progression leading to aggravation of pain, as suggested previously (Collin et al., 1993; Colpaert, 1996), or by an excessive enhancement of pain sensitivity induced by repeated opiate administration, as observed in this study. In this respect, apparent tolerance to the opiate analgesic effect observed in intermittent heroin-treated rats appears as a by-product resulting from a pain sensitization process.
> The relationships between apparent tolerance, pain sensitization, and naloxone-precipitated hyperalgesia observed in intermittent heroin-treated rats lead to the assumption that if the sensitization process was prevented before the drug effect was initiated, apparent tolerance, pain sensitization, and naloxone-precipitated hyperalgesia could not be expressed. Numerous studies demonstrated that the NMDA receptor antagonist may prevent the expression of sensitization processes (Stewart and Badiani, 1993), especially pain sensitization leading to hyperalgesia, allodynia, and spontaneous pain (Haley and Wilcox, 1992; Mao et al., 1995; Coderre and Katz, 1997). Of note is the observation that m-opioid receptor stimulation triggers the activation of NMDA receptors by reducing Mg21 blocking via intracellular protein kinase C (PKC) activation (Chen and Huang, 1991, 1992). It has been suggested that the subsequent increase of intracellular Ca21 concentration further stimulates PKC activity leading to a lasting enhancement of glutamate synaptic efﬁciency in a positive feedback (Mao et al., 1995; Coderre and Katz, 1997).
> The present study shows that the NMDA receptor antagonist MK-801, when administered just before heroin, not only precluded sustained heroin-induced delayed hyperalgesia as described previously (Laulin et al., 1998, 1999) but also prevented the effectiveness of a small heroin dose to induce a sustained hyperalgesia in heroin-deprived rats, a critical criterion for sensitization. No apparent tolerance was observed. Moreover, MK-801 also prevented naloxone effectiveness in precipitating hyperalgesia in heroin-deprived rats that had recovered their pre-drug nociceptive threshold value. This indicates that naloxone-precipitated hyperalgesia is the result of the sharp breakdown of an equilibrium between opioid-dependent analgesic systems and NMDA-dependent pronociceptive systems. Because NMDA receptor antagonists can prevent the development of sensitization and long-term potentiation (Kullmann and Siegelbaum, 1995; Hudspith, 1997), our results lead to the hypothesis that pain sensitization and some signs of withdrawal such as hyperalgesia are issued from a neuroadaptive continuum triggered by opioid receptor stimulation in which NMDA-dependent pronociceptive systems play a critical role.
> 
> _Source: J Neurosci. 2001 Jun 1;21(11):4074-80.
> Evelyne Ce ´le ` rier, Jean-Paul Laulin, Jean-Benoı ˆt Corcuff, Michel Le Moal, and Guy Simonnet
> Institut National de la Santé et de la Recherche Médicale U 259, Psychobiologie des Comportements Adaptatifs, Université Victor Ségalen Bordeaux 2, 33077 Bordeaux, France._


Might not be the most recent findings, but I still found it worth mentioning. Again, this is a short term study though...


MyDoorsAreOpen said:


> For my internal medicine rotation, I wrote a paper on NMDA receptor antagonism in the treatment of chronic pain. It seems that these drugs are a sort of 'reset button' on neural memory; tolerance to drugs, chronic pain, and negative thought loops are all forms of reinforced neural pathways. The reinforcement comes from the neurons inserting more NMDA receptors (actually ion channels) in the cell membrane, so that they can depolarize and fire more easily. Jamming these ion channels brings the cells back to their original firing threshold.
> 
> I think the clinical use of DXM and ketamine (to say nothing of any PCP analogs!) will always be controversial, because people not ready for an all-out mystical experience (that's most people), tend to find them highly frightening in psychoactive doses. Memantine, however, is a gem -- it's highly specific to the NMDA receptor, unlike the others just mentioned. I think it has great potential for treating a number of psychiatric and psychosomatic illnesses which are a result of reinforcing the wrong neural pathways over time.
> 
> I love theanine, too. 200mg of that, and I feel like a million dollars. I'd recommend anyone with minor depression, anxiety, or anger management issues start taking it.


Hehe I'm planning to do a study on NMDA antagonists for my dissertation (which still lies a couple years in the future). Something about chronic use of high doses or abuse would be interesting, I haven't seen mcuh on that aside from old studies regarding pcp.

I just can't imagine that this jamming of ion channels can go on for very long, looking at how I felt after abusing nmda antagonists for a few years and seeing how massive the tolerance to those drugs itself can become... :/ I still appreciate their wide range of effects, their impressive value as the seemingly most effective antidepressants of our time, the magical state a high dose of Ketamine or Phencyclidine puts me in... But I doubt it can be made into a habit of chronic use, at least with those antagonists which are known to man as of now and are known to be effective over the short term.

In other words, I'd appreciate anyone posting their experiences with long term use. The people I know who use a lot of NMDA antagonists usually have massive tolerance for every other drug they take on a frequent basis... People who are trying this tolerance reduction right now (and I am among those) might wake up to realize their drug expenses have exploded and the exact opposite of what they intended has happened. There are no long term studies and we are playing with fire making ourselves subject to studies of psychotropic drug interactions, I just hope everyone is perfectly aware of that.


My hypothesis would be something along the lines of: Long term use of certain NMDA antagonists, will lead to quicker developement of tolerance towards certain drugs (only drugs that have been consumed during the episode of nmda antagonist use?).
It'll probably lead to a whole lot more changes in neuronal and behavioural adaptation processes...
The little evidence I have so far is looking at (polytoxicomanic) people I know who have actually been abusing nmda antagonists for a longer period of time and also looking at myself who hasn't been as successful at decreasing amphetamine tolerance with DXM (and ketamine) as some people here. While it does seem to have the described effect, it is only of a short duration.

We should probably start a thread solely to compare the tolerance towards various drugs between those users who have been extensively abusing nmda anatagonists and those who have not. I'm almost certain we will see a tendency from lower tolerance in the occasional user and those who are relatively new to nmda antagonists towards an extraordinarily high development of tolerance in the chronic user of ketamine and dextrometorphan.

Bluelight would be the perfect place to conduct surveys like this, in fact if creating surveys like that would be a little easier, I'm sure we'd see a lot of them popping up on the forums.


----------



## BananasAndOranges

MeDieViL said:


> I would like to add my experience regarding daily use of GBL on memantine, i take around 100ml a week and after several months didnt experience any tolerance whatsoever, i did have occasional breaks of a couple weeks because i allways ran out too soon, but i definatly should have build up a tolerance by now consider i use it alot and use it every day.
> 
> Physical addiction is something ive allways avoided on GBL, because i never took it during the day in the past, even without memantine, the timefrime you take it plays a major role in physical addiction to G imo, with not taking it for sleep too being very important.
> 
> Yeah 40mg is the dose were memantine really works, anything lower and it just seems to slow tolerance quite a bit but thats all.


taking g for sleep is how the addiction really started for me. I dunno about you. How many years have you been doing it? I always got up to 2 10ths a day and could often start on the next bottle.......it was shite!


----------



## MeDieViL

BananasAndOranges said:


> taking g for sleep is how the addiction really started for me. I dunno about you. How many years have you been doing it? I always got up to 2 10ths a day and could often start on the next bottle.......it was shite!



I NEVER take G for sleep, wich is rather important to avoid addiction, i can allways sleep after the doses wear off tough.

Ive been taking GBL with occasional breaks of a couple weeks since 2008, i only started using 100ml a week on memantine tough, and after months i have yet to notice tolerance, i would imagine memantine also puts a brake on the development of physical addiction.


----------



## BananasAndOranges

MeDieViL said:


> I NEVER take G for sleep, wich is rather important to avoid addiction, i can allways sleep after the doses wear off tough.
> 
> Ive been taking GBL with occasional breaks of a couple weeks since 2008, i only started using 100ml a week on memantine tough, and after months i have yet to notice tolerance, i would imagine memantine also puts a brake on the development of physical addiction.


I cant/couldnt for me it was like I had to take enough to black out which for most is a dose but for me it was like a few bottles and around the clock. my body would feel it everytime it wore off and i would wake up every 3 hours and dose repeatedly. it was going on for like a year or a bit less but lets say a year....awfullly addicting stuff and the wds were sooooo unbearable.....try never to get one...its like being really uncomfortable and having no appetite i guess just like a opiate withdrawal but not puking except I puked because i was ending up taking 3 10ths to 4 a day. which is a LOT if you know how its measured and im sure you do. fucks your stomach UP


----------



## BananasAndOranges

MagickalKat777 said:


> So my withdrawal is just not going fast enough at 40mg... would 50, 60mg make a bigger impact or should I switch to Delsym for NMDA antagonism instead? I noticed that Delsym made me cut my Valium the second day I was on it...


WHAT THE FUCK IS DELSYM and why would you take it I saw this the other day at walgreens everywherreee


----------



## avcpl

MeDieViL said:


> Yeah 40mg is the dose were memantine really works, anything lower and it just seems to slow tolerance quite a bit but thats all.




So for mild/moderate MDMA tolerance, how many days at 40mg memantine would you recommend for tolerance reversal?

And, should you take the MDMA while the memantine is in your system, or would it matter (i.e.   a week or two buffer period with no memantine?)






.


----------



## ferinox

I decided to add delsym to my plan to taper off of 100 mg of  oxycodone daily. It was a fairly rapid taper with a 50% decrease every 4 days. Not only was it easy, I actually started getting high again on the lower doses to my surprise. Is that unusual or can a NMDA antagonist really be that effective? I also had only been on opiates for 2 months if that makes any difference.


----------



## MeDieViL

ferinox said:


> I decided to add delsym to my plan to taper off of 100 mg of  oxycodone daily. It was a fairly rapid taper with a 50% decrease every 4 days. Not only was it easy, I actually started getting high again on the lower doses to my surprise. Is that unusual or can a NMDA antagonist really be that effective? I also had only been on opiates for 2 months if that makes any difference.



They really do work mate, its quite incredible actually.


----------



## MeDieViL

avcpl said:


> So for mild/moderate MDMA tolerance, how many days at 40mg memantine would you recommend for tolerance reversal?
> 
> And, should you take the MDMA while the memantine is in your system, or would it matter (i.e.   a week or two buffer period with no memantine?)
> 
> 
> 
> 
> 
> 
> .



Its completely unclear wheter they can slow mdma tolerance, let alone reverse tolerance, 40mg mem seems to be the sweet spot for amp tolerance, give it a try and let us know.


----------



## avcpl

MeDieViL said:


> Its completely unclear wheter they can slow mdma tolerance, let alone reverse tolerance, 40mg mem seems to be the sweet spot for amp tolerance, give it a try and let us know.



Sorry, I do realize that; I'm just looking for a place to start. 

So if I where to follow a schedule for amp tolerance, what would that entail?


----------



## MeDieViL

avcpl said:


> Sorry, I do realize that; I'm just looking for a place to start.
> 
> So if I where to follow a schedule for amp tolerance, what would that entail?



For amphetamine its recommened to titrate up to 40mg of memantine and taking a small break of amp untill the memantine adaptation phase is over.


----------



## avcpl

MeDieViL said:


> For amphetamine its recommened to titrate up to 40mg of memantine and taking a small break of amp untill the memantine adaptation phase is over.



I would imagine the memantine adaptation phase will be different for everyone, but may I ask how long yours was so that I have a point of reference?  (and you too MagickalKat?).

I'm particularly intrigued because part of the diminished effects of mdma for me have been lack of an amp feeling and lack of pupil dilation; it will be interesting to see if memantine restores those aspects...


----------



## MeDieViL

It inhibits amphetamine for pretty much a full week in my case, after witch the adaptation phase is over and tolerance prevention/potentation takes place.


----------



## MeDieViL

http://www.bluelight.ru/vb/showthread.php?t=519434&highlight=memantine


----------



## avcpl

MeDieViL said:


> It inhibits amphetamine for pretty much a full week in my case, after witch the adaptation phase is over and tolerance prevention/potentation takes place.



A week at 40mg/day? or a week total (starting and building up to the 40mg)?

Sorry to be such a pain in the ass! But, I do appreciate your responses!


----------



## MeDieViL

NP mate.

A week at 40mg.


----------



## avcpl

lol, thanks.  I'm just trying to calculate how much I need to have on hand for the trial. A week at 40mg for me and my wife would be 56 (10mg) pills minimum (plus what it takes for us to build up to that dose). Kind of sensitive to the brain-fog feeling myself, so it may take a while at small increments. 

Again, thanks so much!


----------



## MeDieViL

As long you keep us updated mate!

Damn, i ran out of memantine a while ago, i am sleep deprived and using amphetamine day 2 amp barely works anymore, i remember that of the old days but this really shows how good memantine was working for me, my amp allways stayed working as strong.


----------



## Tomer

Med-

Would taking DXM a few hours prior to MDMA ingestion potentiate the experience?  45-60 MG Dose of DXM Extended prior to the MDMA (Delsym).  Let me know what you think

Cheers


----------



## MeDieViL

Tomer said:


> Med-
> 
> Would taking DXM a few hours prior to MDMA ingestion potentiate the experience?  45-60 MG Dose of DXM Extended prior to the MDMA (Delsym).  Let me know what you think
> 
> Cheers


Yes, and not a little bit! A pretty deadly roll it can become.


Dont take DXM with MDMA mate, order memantine.


----------



## MeDieViL

I would also like to request that those that arent getting as impressive results to report their experience too, to get a good idea on the effectiveness of NMDA antagonists, i know that with this kind of thing some members may not feel like reporting their experience if it didnt work.


----------



## MeDieViL

More ppl need to try this! Comeone guys, imagin using all your drugs with barely a tolerance, give this shit a try!

I'm gonna make a small thread about this in the MDMA section, many have lost the magic and i bet a few members would try it, we really need more reports on MDMA!


----------



## MeDieViL

More reports, those where posted on bluelight



> This drug DXM stands for dextromorphan or something. I need you to research its effects on the brain and the nervous system. This is insane.
> 
> Let me try to explain a little bit. It's known as robotussin and its used for coughs and its a dissociative which means it fucks with the central nervous system, but I tried taking 3 times the normal dose in some sort of attempt to reverse my opiate tolerance as ive been going into withdrawal and this is what happened:
> 
> Last night it worked and i got high off a dose of oxycodone i havent been able to feel even since last year.
> 
> But this is even more INSANE like seriously Alicia I want to jump and shout. It's unlocked memories and removed what I can only describe as a brain fog and has unlocked my personality and I feel like a NORMAL HUMAN BEING I feel like MYSELF for the first time in a long time since I started using opiates.
> 
> My theory is that it deactivates the glial cells in the CNS that are responsible for producing whats called 'tolerance' to opiates and the endogenous opiods produced by the brain. In other words, the 'brain damage' (aka tolerance) i've incurred with long term opiate use has been temporarily removed by this otc dissociative drug, DXM. I can FEEL my brains natural pleasure chemicals again and it feels so great. But the thing is NO ONE UNDERSTOOD. After long term opiate abuse at school I was suffering from constant depression and my parents put me in rehab counseling/psychologist/psychiatrist. the psychiatrist gave me SSRI's and they did jack shit but THIS WORKS.
> I was depressed and fiending for opiates because I was so overly tolerant to the family of neurotransmitters known as opioids. Apparently these chemicals are as much involved with long term memory and basically EVERYTHING as they are with pleasure.
> I cannot believe this, but at the same time, the body builds its own tolerance to DXM, so it's not like I can feel like myself unless I start abusing DXM to reverse opiate tolerance which obviously won't work after a long period of time.
> 
> I feel excitement and all kinds of other emotions I haven't known for a year at least. It's insane, it's like I just woke up out of a coma.





> Good to hear you feel better I would not do opies anymore if i had your chance. they have ruined enough shit for 6 lifetimes.....
> I dont believe glial cells/neurons can be "deactivated". Activated brain areas create neurons to form networks to tighten response, but die off if not used. Short term memory is the best example.
> Possibly antagonism, but I would look into the memory centers of the brain.
> 
> Go borrow a fMRI machine from a hospital. jk
> 
> I was hoping someone could shed a little light on how it has managed to temporarily cure my opiate tolerance and everything that came with it. Part of formthis message is copied from something I sent to an ex girlfriend whos attending Harvard in the hopes that she could do some published research on the topic and spread the word.
> 
> The reason I'm posting it here is because in the past 2 or 3 years of opiate addiction bluelight has given me an amazing resource for harm reduction and drug information and I want to share this with opiate addicts seeking help on this forum.
> 
> By the way, before I paste the edited version of what I sent her, I am currently experiencing no withdrawal symptoms thanks to DXM and I was sick as a dog yesterday with no oxycodone left to save my ass. (Took about 4.5 hours after taking my 55mg dose of DXM for withdrawal to cease entirely)
> Here's my account of DXM and its effects on reversing opiate tolerance that I sent to my ex:
> 
> 
> 
> Thanks Bluelight. if a mod wants this to be in journals or trip reports I'd ask them to please wait to move it until some users with advanced knowledge of chemistry have read my anecdotal account and possibly verified it with accurate info, thanks!!!


[/QUOTE]
Negative report:


> I'd hate to break it to you (even though it seems it's already been broken) but Dextromethorphan (or any NMDA antagonists for that matter) will play about as big of a role in alleviating opiate/oid withdrawal symptoms as Diphenhydramine, Naproxen and Loperamide do. On a relief factor, it *may* lie somewhere between the OTC remedies and Benzodiazepines/Barbituates.
> 
> Someone with a very mild Codeine addiction would probably benefit from a combination of DXM with the other remedies listed, but a Heroin addict that injects 2+ grams a day for years will not think of it as a 'miracle drug' at all.
> 
> Back when I was that Heroin addict I just spoke of, I tried DXM, Ketamine, PCP, all the OTC methods, Benzos, Barbituates, Clonidine, etc; trying to find the *right* combination for making withdrawal at least somewhat tolerable. Even throwing a Methadone taper into the mix didn't work. The only thing that got me off of Heroin was making my first visit to my PCP (not to be confused with Phencyclidine) in order to get on Suboxone maintenance. When he saw that I was in severe withdrawals 6 hours after injecting 7 'Philly' bags, he put me on 32mg of Suboxone instantly. I went through a pretty nasty withdrawal for about 48 hours, but got back to baseline at around 72 hours. That was 13 months ago and now I am down to 8mg once per day with zero relapses. The only time(s) I've ever felt a craving were after I'd get done with an intense workout and I'd see a vein that originally had collapsed suddenly re-appear, sort of announcing to the monkey in me, "Hey, I'm back! Whatcha got for me?"... anyways, I'll leave it at that.
> 
> Sorry for the long post. I just don't want anybody to see this thread title and get their hopes up without diving deep into the data and personal experiences and go lock themselves in a room with a couple of bottles of cough syrup thinking they'll be "cured" by a "miracle drug".
> 
> By the way, hello everyone. I recognize a few names and posting styles from the old BL, the bee's nest, PhreeX's old board, etc. My account got canned back when BL had the "re-boot" or whatever around 2005(?), so unfortunately I can't access it/it doesn't exist anymore, and I've just been lurking for years.
> 
> Peace!


----------



## MagickalKat777

Well I am down 50% on my valium now but its not comfortable - I may have to go back up or increase the memantine or add Delsym or something.

I get the distinct impression that DXM is more effective for benzos than memantine is but at the same time, I was taking 60mg of Delsym twice a day versus taking 20mg of memantine twice a day so maybe I just need to go up in the mem dose.

Personally, I think Delsym was working quite well with the valium withdrawal though - my tolerance to it was going down when I was on the Delsym and it started on the second or third day... I switched to memantine due to concerns about drug interactions with DXM but I may switch back because memantine has suppressed my breathing when I take too much (up to 60mg a day) and doesn't appear to be working as well as DXM does. Plus I quit taking drugs altogether in order to do my taper as quickly as possible and get back to work.

Can anyone comment on how well DXM works versus memantine for benzo withdrawal? I would imagine that it is superior - I remember that my valium tolerance dropped on its own when I was doing the Delsym whereas the memantine seems to just reduce the withdrawal symptoms (ie., no brain fog, no memory problems, still functional, no panic attacks, but still psychological symptoms like feeling that your heart is going to give out, weird body feelings, but nothing physical to back it up other than random pains).

It seems to be somewhat commonly reported that for whatever reason, DXM users can keep using the drug they are tolerant to and still experience a tolerance reduction but this does not seem to be the case with memantine. 

I guess I may have to just suck it up and switch to the syrup and just make sure to avoid serotonergic drugs, although I wonder how much damage a roll would do with therapeutic levels of Delsym - I won't be trying it though.


----------



## MeDieViL

I wonder wheter ketamine "shock" therapy would work, like in the same way as it works for depression.


----------



## MagickalKat777

I have a gram of ketamine I could experiment with but ketamine lasts such a short amount of time that's its kind of pointless.


----------



## MeDieViL

NMDA antagonists work for tolerance by inducing receptor upregulation, the effects of ketamine last a few weeks for depression, while this has been associated with rapid synaptogenesis this doesnt explain everything as the antidepressants effects disappear rapidly again, perhaps receptor upregulation of differend neurotransmitter systems plays a major role too, in that case a singly high dose of ketamine should reverse tolerance quite a bit to several substancs, after wich you should be able to maintain this with memantine or DXM, however i'm just speculating on this, would be interesting to see how it would work.


----------



## MeDieViL

I highly recommend a heartrate monitor when combining memantine with depressants for the following study i just came across.


> Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.
> Gallini A, Sommet A, Montastruc JL; and the French PharmacoVigilance Network.
> 
> Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire, Hôpitaux de Toulouse, Toulouse, France. adeline_gallini@yahoo.fr
> Abstract
> OBJECTIVE: To review the cardiovascular adverse drug reactions (ADRs) with memantine reported to the French PharmacoVigilance Database.
> 
> METHODS: We reviewed all the observations of cardiovascular ADRs with memantine reported to the French PharmacoVigilance Database up to May 2007. We recorded the characteristics of patients (age, sex and underlying disease) and of ADRs (nature, seriousness, delay in occurrence, evolution, imputability).
> 
> RESULTS: After exclusion of 16 cases, the cardiac origin of which was not clearly assessed, 36 cardiac ADRs with memantine were recorded between its commercialisation in France (July 2003) and May 2007. These ADRs consisted of 18 reports of bradycardia and 18 reports of various cardiovascular ADRs (orthostatic hypotension with fall[6] electrocardiogram perturbations[4] fainting[2] malaise with arterial hypotension[2] arterial hypotension and acute renal failure[1] fatal heart failure[1] sudden death[2]). Among the 18 reports of bradycardia, 7 cases occurred with memantine as the sole suspected drug and all but one resolved after memantine's discontinuation.
> 
> CONCLUSION: Cardiovascular properties of memantine seem to be complex and remain quite unclear. Despite its drawbacks and its descriptive design, our study suggests that memantine could determine some cardiac ADRs, especially bradycardia; the mechanism of which remains unexplained.


----------



## 23536

MeDieViL said:


> I would also like to request that those that arent getting as impressive results to report their experience too, to get a good idea on the effectiveness of NMDA antagonists, i know that with this kind of thing some members may not feel like reporting their experience if it didnt work.



of those attempting DXM, ~5-10% will not get the NMDA antagonist effect.  DXM's affinity for the PCP site measures at Ki = 7253 nM, so people who cannot adequately convert it to DXO will see little benefit.


----------



## MagickalKat777

After my pulse skyrocketed to 180 BPM the other night from 150mg of known clean MDMA (moon rocks) and 235mg of known-clean mescaline HCl, I have decided that I am going to switch to DXM. I was going to take myself to the hospital but instead I drank a bunch of whiskey and passed out shortly after. A rise in pulse and BP was noted with a previous roll on memantine, before the withdrawal process had started, so it wasn't just withdrawal.

I either need to stay completely sober when I am on memantine  - taper or not - or I need to get off the memantine and get on something that is safer as long as it isn't combined with serotonin releasing agents. Mushrooms, for example, should be perfectly safe on DXM, as should most other tryptamines (except maybe aMT) and phenethylamines (minus 2C-T-7 and the aforementioned serotonin releasing agents).


----------



## avcpl

Wow mk, glad you are alright! Thanks for posting that; I just assumed that when I worked up to 40mg of memantine and adapted to it, it would be ok to take my standard dose of MDMA. I guess, I'll take a week or more off first to be safe. 

But for tolerance prevention, don't you have to take the drug with the memantine?


----------



## MagickalKat777

I tend to have any adverse reaction that is clinically possible - my body really dislikes pharmaceutical drugs so don't take my word as the final word, it was more a word of caution - but cardiac events do appear to be a problem with memantine.

I switched to DXM starting last night by taking 5mL of Delsym at midnight. I then SKIPPED my Valium dose and took another 5mL at 6AM then fell asleep about 11AM. I woke up about 3PM, which meant I missed my afternoon dose of Valium as well and then about 4:30 I finally took 5mg of Valium and that's all I've had today. I took another 5mL of Delsym when I woke up and another 5mL at 7:30 or so and will take another 5mL at midnight. Normally I'd have taken 20mg of Valium in this time period so there is definitely something to dextromethorphan versus memantine. I should also note that I have experienced no respiratory suppression or heart abnormalities since I stopped taking the memantine, even with the extreme decrease in Valium.

Even more amazing is the fact that when all this went on with the heart racing out of control on the MDMA/Mescaline combo and the drinking that ensued, I ended up taking a full extra 20mg of Valium that day but I'm still able to come down so quickly off of it the day after the fact.

As for the tolerance prevention, just go back on the memantine after you come down from the MDMA. Memantine has quite a long half-life though so there's still a chance that a good bit of it could be in your system even a week later. Even at the low side of 60 hours, that's 2.5 days before your blood level of memantine is halved and another 2.5 days before its quartered, meaning that it takes 5 days to get down to 10mg plasma levels after taking 40mg. On the high end, the half life is 100 hours so you'd be looking at just over 4 days before your plasma levels would hit 20mg after dosing 40mg.

Either way, it seems that all of the NMDA antagonists have the ability to cause severe CNS issues including respiratory failure, heart attack, and stroke, so just be careful with them. Ketamine has been known to cause significant increases in pulse and blood pressure and everyone knows that recreational levels of dextromethorphan cause tachycardia and hypertension.

All that being said, the 120mg of dextromethorphan polisterex I have taken is having less of an impact on my pulse and blood pressure than 40mg of memantine did.


----------



## Smokey McPot

My oxy tolerance is way out of hand lately and I want to try to lower it using DXM.

How much DXM should I be taking and how often/ when in relation to when i take my opiates should I be taking it? For those that have been successful with this, how long did it take to notice a lowering of tolerance?

I know nobody really knows this stuff for sure but could someone give me a regimen of sorts to try/ start with and Ill post my results with it weather it works or not, for the sake of science of course.

Also does it matter if im using DXM polystirex or DXM Hbr? can i use any preparation with dxm in it because the doses are relatively low or should i use something where DXM is the only active?


----------



## M Brace

MeDieViL said:


> NMDA antagonists work for tolerance by inducing receptor upregulation, the effects of ketamine last a few weeks for depression, while this has been associated with rapid synaptogenesis this doesnt explain everything as the antidepressants effects disappear rapidly again, perhaps receptor upregulation of differend neurotransmitter systems plays a major role too, in that case a singly high dose of ketamine should reverse tolerance quite a bit to several substancs, after wich you should be able to maintain this with memantine or DXM, however i'm just speculating on this, would be interesting to see how it would work.



Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own?  Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?  

What about DXM?  I've read about people using DXM the day before taking mdma and finding that it restores some magic.  

Does the benefit remain after the nmda antagonist has left the building?  Or is it necessary to consume it in conjunction with the substance it's supposed to help with?


----------



## crOOk

MeDieViL said:


> NMDA antagonists work for tolerance by inducing receptor upregulation, the effects of ketamine last a few weeks for depression, while this has been associated with rapid synaptogenesis [...]


I thought NMDA receptors were important for neuroplasticity, does the synaptogenesis happen once the effects have worn off as some sort of rebound effect?


----------



## MeDieViL

crOOk said:


> I thought NMDA receptors were important for neuroplasticity, does the synaptogenesis happen once the effects have worn off as some sort of rebound effect?



It occurs rapidly as ketamine activates the mTOR pathway.


----------



## avcpl

M Brace said:


> Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own?  Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?
> 
> What about DXM?  I've read about people using DXM the day before taking mdma and finding that it restores some magic.
> 
> Does the benefit remain after the nmda antagonist has left the building?  Or is it necessary to consume it in conjunction with the substance it's supposed to help with?



Great questions!!!!! I would love the answers to these as well; I would also be interested in knowing if a memantine/DXM combo would be more effective than either one alone...






.


----------



## bben

Would nmda antagonists lessen the euphoria if used during dosing with for example amphetamine. I assume it would as it would lower glutamate activity which is needed in the VTA and NAC for euphoria as much or more than dopamine. So i would worry about nmda antagonists dampening the euphoria of any drug that derives reward through the glutamatergic system... aka all stimulants and opiates.


----------



## Cloudy

uncompetitive nmda-antagonist do not block the binding site of glutamate, and it actually needs the binding of glutamate to it's nmda receptor.


----------



## bben

Cloudy said:


> uncompetitive nmda-antagonist do not block the binding site of glutamate, and it actually needs the binding of glutamate to it's nmda receptor.



gotcha i wanted to know that.


----------



## Cloudy

Not to mention that NMDAr's are not the only receptors that are excitatory, which glutamate is an agonist for


----------



## negrogesic

While I found IV ketamine and nitrous oxide helpful for opioid withdrawal, DXM simply gave me some unwanted CNS-stimulation with inconvenient psychedelic effects. 

If you are to use DXM to aid opioid withdrawal, do NOT use it for detoxing off of tramadol, pethidine, and other serotonergic opioids...


----------



## MeDieViL

Smokey McPot said:


> My oxy tolerance is way out of hand lately and I want to try to lower it using DXM.
> 
> How much DXM should I be taking and how often/ when in relation to when i take my opiates should I be taking it? For those that have been successful with this, how long did it take to notice a lowering of tolerance?
> 
> I know nobody really knows this stuff for sure but could someone give me a regimen of sorts to try/ start with and Ill post my results with it weather it works or not, for the sake of science of course.
> 
> Also does it matter if im using DXM polystirex or DXM Hbr? can i use any preparation with dxm in it because the doses are relatively low or should i use something where DXM is the only active?



I'm not really sure about dosing as i dont really know the DXM formula's, there slow fast acting? powder and cough syrop etc, id take a look at the anecdotal reports scattered over the thread and then use simular doses, it seems delsym is most popular for this purpose.


----------



## MeDieViL

M Brace said:


> Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own?  Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?
> 
> What about DXM?  I've read about people using DXM the day before taking mdma and finding that it restores some magic.
> 
> Does the benefit remain after the nmda antagonist has left the building?  Or is it necessary to consume it in conjunction with the substance it's supposed to help with?



I noticed the exact same thing with DXM, took a recreational dose and the next day is completely fucked of MDMA, rather then getting a shitty feeling wich i started doing everytime i took mdma because of massive abuse.

Yes the benefit should remain after the NMDA antagonist has been withdrawn as they upregulate a bunch of receptors implicated in drug reward, atleast thats how it looks in theory, ketamine after mdma also abolishes the crash for most, indicating it just upregulates receptors again that have been downregulated by MDMA.


----------



## MeDieViL

bben said:


> Would nmda antagonists lessen the euphoria if used during dosing with for example amphetamine. I assume it would as it would lower glutamate activity which is needed in the VTA and NAC for euphoria as much or more than dopamine. So i would worry about nmda antagonists dampening the euphoria of any drug that derives reward through the glutamatergic system... aka all stimulants and opiates.



No, in fact they are known to potentiate it, while they do act as NMDA antagonists, they dont really affect glutamate (atleast some cause an increase in glutamate) and im not sure what role NMDA receptors temself play in drug induced reward, regardless excess blockage probably causes negative effects, but the NMDA antagonism doesnt come close to the nmda antagonist of certain drugs of abuse, wich are highly euphoric combined with other stuff (think ketamine with mdma etc).


----------



## MeDieViL

Check out nuke's post:
http://www.bluelight.ru/vb/showpost.php?p=9192577&postcount=18

Which is interesting is that regards to opiates NMDA antagonists dont upregulate the mu opioid receptors but act on a downstream mechanism.


----------



## bben

MeDieViL said:


> Check out nuke's post:
> http://www.bluelight.ru/vb/showpost.php?p=9192577&postcount=18
> 
> Which is interesting is that regards to opiates NMDA antagonists dont upregulate the mu opioid receptors but act on a downstream mechanism.



i think i remember hearing something about iNOS inhibitors preventing opiate tolerance as well. Curcumin is an iNOS inhibitor so this likely plays a role along with nmda antagonism, perhaps a more important role.


----------



## MeDieViL

bben said:


> i think i remember hearing something about iNOS inhibitors preventing opiate tolerance as well.



Yes and proglumide and ultra low dose naltrexone, however the last 2 didnt really pan out in humans, causing rather incosistent results for those that tried it, i think nmda antagonists and possibly curcumin are the best options.


----------



## bben

MeDieViL said:


> Yes and proglumide and ultra low dose naltrexone, however the last 2 didnt really pan out in humans, causing rather incosistent results for those that tried it, i think nmda antagonists and possibly curcumin are the best options.



yes since curcumin has 2 mechanisms to lower tolerance. possibly more, if only we could get it to hit the blood stream and stay bcm 95 is ok for it.


----------



## avcpl

Are there any interactions between memantine and Saint John's Wort?  (I've been searching but can't find any info; there does seem to be between SJW and DXM though...)


----------



## MeDieViL

avcpl said:


> Are there any interactions between memantine and Saint John's Wort?  (I've been searching but can't find any info; there does seem to be between SJW and DXM though...)



No, that combo is safe.


----------



## MagickalKat777

MeDieViL said:


> I noticed the exact same thing with DXM, took a recreational dose and the next day is completely fucked of MDMA, rather then getting a shitty feeling wich i started doing everytime i took mdma because of massive abuse.
> 
> Yes the benefit should remain after the NMDA antagonist has been withdrawn as they upregulate a bunch of receptors implicated in drug reward, atleast thats how it looks in theory, ketamine after mdma also abolishes the crash for most, indicating it just upregulates receptors again that have been downregulated by MDMA.



Couldn't this be explained by DXM's nonselective serotonin reuptake inhibition effects though? I don't think the amount of time that DXM inhibits serotonin reuptake has been established but I've known people who (stupidly) take dextromethorphan before rolling to increase the effects of the roll exponentially.


----------



## MeDieViL

MagickalKat777 said:


> Couldn't this be explained by DXM's nonselective serotonin reuptake inhibition effects though? I don't think the amount of time that DXM inhibits serotonin reuptake has been established but I've known people who (stupidly) take dextromethorphan before rolling to increase the effects of the roll exponentially.



Well my own personal strategy to get more serotonine was like popping 5 extra pills with 120mg MDMA at once, i abused the hell out of MDMA, think doing that twice a week, my receptors COMPLETELY downregulated, if DXM increases serotonine enough to return the magic then a couple extra pills should have done too.


----------



## MeDieViL

Ive started DXM today, i take around 100ml GBL a week, i ran out of memantine, my response to GBL changed to either sedation with barely any euphoria or brainzaps, restarted dex today, barely feel a thing, effects are greatly diminished because of my last binge without memantine, lets see how this works, this is my first time using DXM like this.


----------



## MeDieViL

Avoid combining cough syrop and GBL on a empty stomach lol


----------



## MeDieViL

Allready dont notice any G brainzaps anymore, seems this was related to tolerance, also the euphoria is back! Dex potentiated too, DXM is definatly potent shit!


----------



## MeDieViL

crOOk said:


> Oh niceness, I started reading about this very recently for two reasons:
> 
> 1) NMDA receptors are fascinating and I'd love to research them in the future.
> 
> 2) I started taking amphetamine sulfate orally, am planning to keep doing so for the next decade and am worried that tolerance is going to keep increasing. Since I started taking Magnesium citrate 3 weeks ago sensitivity hasn't been changing it seems (~1g per day dissolved in water, a ridiculous amount of actual Mg considering the size of that ligand).
> I was considering to switch to DXM HBr 30mg per day for a few weeks and see if tolerance can actually be decreased that way.
> 
> I hope I'll have found out more once I have time to browse through those links.
> 
> Thank you!
> 
> Edit: Most excellent post MeDieViL, thank you very much!! I'll order some DXM right now! They only cost 2.48€ per 20caps here in Germany, that's nothing really even if it turns out I need 60mg per day! I'll still be at less than 10 Euros per month...



How did this regime work for you mate?

Cheers


----------



## MagickalKat777

MeDieViL said:


> Allready dont notice any G brainzaps anymore, seems this was related to tolerance, also the euphoria is back! Dex potentiated too, DXM is definatly potent shit!



I've found DXM to work better than memantine in my trials and IMO, the shorter half life of DXM is a GOOD thing because any adverse events would be over with rather quickly whereas they could be prolonged with memantine for some time.


----------



## burn out

i just read this whole thread as i am interested in the possibility of treating protracted benzo withdrawals with this method. should i just start taking dxm every day and see what happens? i have ketamine also, although in limited supply.


----------



## MeDieViL

MagickalKat777 said:


> I've found DXM to work better than memantine in my trials and IMO, the shorter half life of DXM is a GOOD thing because any adverse events would be over with rather quickly whereas they could be prolonged with memantine for some time.



Yeah it seems alot more potent for this, i wish there was a non serotogenic version of DXM.


----------



## crOOk

MeDieViL said:


> How did this regime work for you mate?
> 
> Cheers


Seems to work fine, tolerance has levelled out, I'm at a slightly lower amp dose than I was when I started, while before that tolerance was constantly increasing. I'm taking 30-60mg DXM 1-3times per week so far, along with my amp dose and a fat dose of Magnesium (eyeballed).

The following is an article from 2001, so it's not really up-to-date, but still offers some help in understanding the mechanism of nmda-antagonists antidepressant effects and possibly their tolerance decreasing effects as well.



> *N-Methyl-D-aspartate Receptors Regulate a Group of Transiently Expressed Genes in the Developing Brain*
> Mammalian brain development requires the transmission of electrical signals between neurons via theN-methyl-d-aspartate (NMDA) class of glutamate receptors. However, little is known about how NMDA receptors carry out this role. Here we report the first genes shown to be regulated by physiological levels of NMDA receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1(NARG1), NARG2, and NARG3. These genes share several striking regulatory features. All three are expressed at high levels in the neonatal brain in regions of neuronal proliferation and migration, are dramatically down-regulated during early postnatal development, and are down-regulated by NMDA receptor function. NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a yeast N-terminal acetyltransferase that regulates entry into the Go phase of the cell cycle. The results suggest that highly specific NMDA receptor-dependent regulation of gene expression plays an important role in the transition from proliferation of neuronal precursors to differentiation of neurons.
> 
> Long before synaptic networks are fully established, electrical activity present in developing neurons regulates neuronal differentiation (1-4). In particular, electrical activity mediated by the NMDA1 class of glutamate receptors is required for normal neuronal development. Loss of NMDA receptor function during development increases neuronal cell death (5), prevents the formation of precise neural circuits (6, 7), diminishes respiration and feeding (8-10), and has been implicated in fetal alcohol syndrome (11) and schizophrenia (12). NMDA receptor function can also regulate neuronal proliferation (13) and migration (14). Despite the importance of NMDA receptors for normal development and adult brain function, knowledge of molecular mechanisms regulated by NMDA receptors in developing neurons is rudimentary.
> _Source:J Biol Chem. 2001 Apr 27;276(17):14257-63. Epub 2001 Jan 31.
> N-methyl-D-aspartate receptors regulate a group of transiently expressed genes in the developing brain.
> Sugiura N, Patel RG, Corriveau RA.
> Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA._


In short: There are 3 genes that are highly expressed (suggesting they contribute to the developement of those neurons) in developing neurons of the newborn's brain. These genes are downregulated by NMDA receptor activity!

While two of these 3 genes were unknown when this was published, the third seems to be the equivalent to a gene found in yeast, that is responsible for inducing the G0 phase of cells. G0 is the phase were cells will not devide themselves any further.

It still doesn't make sense to me, but this sure is helpful. 

On another note: Ethanol use seems to have an upregulating influence on NR2b gene transcription. An epigenetic mechanism is suggested here.
Booze->More NMDA 2b receptors

Btw looking at how I've developed a form of tolerance to some drugs, specifically dissociatives and psychedelics, these were much more persistant, less quickly reversible than say pot tolerance. Epigenetic mechanisms?

The epigenetic mechanisms referred to are, you've probably guessed it, methylation and demethylation of CpG sites in the regulatory areas of the mentioned gene. (Methylation of C5 in Cytosine; CpG=Cytidine+phosphate+Guanosin, one of the sequences in our dna/rna; Regions that enhance or silence expression of a gene are usually very rich in these CG-sequences and methylation of Cytosine in position 5 is thought to block these enhancing or silencing function by preventing the responsible specific transcription activators to bind to them).

And indeed it could be shown that booze induced demethylation of these areas, thereby enabling increased occupation of these DNA-binding sites and in consequence increased transcription of the NR2b gen, leading to  higher density of NMDA 2b receptors.

Here's the publication:


> *The Site Specific Demethylation in the 5′-Regulatory Area of NMDA Receptor 2B Subunit Gene Associated with CIE-Induced Up-Regulation of Transcription*
> Background
> 
> The NMDA receptor represents a particularly important site of ethanol action in the CNS. We recently reported that NMDA receptor 2B (NR2B) gene expression was persistently up-regulated following chronic intermittent ethanol (CIE) treatment. Increasing evidence that epigenetic mechanisms are involved in dynamic and long-lasting regulation of gene expression in multiple neuroadaptive processes prompted us to investigate the role of DNA methylation in mediating CIE-induced up-regulation of NR2B gene transcription. To dissect the changes of DNA methylation in the NR2B gene, we have screened a large number of CpG sites within its 5′-regulatory area following CIE treatment.
> Methods
> 
> Primary cortical cultured neurons were subjected to ethanol treatment in a CIE paradigm. Bisulfite conversion followed by pyrosequencing was used for quantitative measurement and analysis of CpG methylation status within the 5′-regulatory area of the NR2B gene; chromatin immunoprecipitation (ChIP) assay was used to examine DNA levels associated with methylation and transcription factor binding. Electrophoretic mobility shift assay (EMSA) and in vitro DNA methylation assays were performed to determine the direct impact of DNA methylation on the interaction between DNA and transcription factor and promoter activity.
> Results
> 
> Analysis of individual CpG methylation sites within the NR2B 5′regulatory area revealed three regions with clusters of site-specific CpG demethylation following CIE treatment and withdrawal. This was confirmed by ChIP showing similar decreases of methylated DNA in the same regions. The CIE-induced demethylation is characterized by being located near certain transcription factor binding sequences, AP-1 and CRE, and occurred during treatment as well as after ethanol withdrawal. Furthermore, the increase in vitro of methylated DNA decreased transcription factor binding activity and promoter activity. An additional ChIP assay indicated that the CIE-induced DNA demethylation is accompanied by increased occupation by transcription factors.
> Conclusions
> 
> These results suggest an important role of DNA demethylation in mediating CIE-induced NR2B gene up-regulation, thus implicating a novel molecular site of alcohol action.
> _Source: Mei Qiang, Ashley Denny, Jiguo Chen, Maharaj K. Ticku, Bo Yan, George Henderson Research Article, published 20 Jan 2010
> doi:10.1371/journal.pone.0008798_


I think this one is free. For the other one feel free to write me.
http://tinyurl.com/mightbefreedontknow


----------



## crOOk

Ok here it comes. This is some heavy shit. Today we learnt about cytosine methylation of cytosine in CG-rich areas responsible for enhancing gene-transcription. I immediately (in thought) came up with the hypothesis that NMDA-antagonists might interfer with methylation through some unknown route. I head home, google a bit, post above post, come out a bit more knowledgable but still unsatisfied with an unquenched thirst for deeper understanding of the mechanics.

Back to uni, back home, gone half insane in the process I google again and come up with this: BÄBÄÄÄM!
Here it goes, so hold on tight.



> *Cortical DNA methylation [insert drumroll] maintains remote memory [insert massive drumbeat!]*
> A behavioral memory’s lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.
> 
> _Source: Nature Neuroscience, Volume: 13, Pages: 664–666, 2010
> doi:10.1038/nn.2560
> Props go out to my homies of whom at least one or two (or at least their employees) worked their asses off to find this out:
> Courtney A Miller, Cristin F Gavin, Jason A White, R Ryley Parrish, Avinash Honasoge, Christopher R Yancey, Ivonne M Rivera, María D Rubio, Gavin Rumbaugh & J David Sweatt
> Props and much love also go out to all the rats in the house who had fear injected into them in wicked human experiments!_


And indeed this proved to be true. But not only that, NMDA antagonist MK-801 proved to reverse the methylation of CpG rich regulatory areas for calcineurin genes in the prefrontocortex, meaning the (fear-)memories acquired by the rats could not be maintained after MK-801 had been injected. Lucky rats I say!

This reinforces my idea of NMDA antagonists interfering with DNA methylation and also suggests that drug tolerance can manifest through modification of the very essence of life: DNA!


----------



## MyDoorsAreOpen

crOOk said:


> Additionally, it is a possible explanation why russians can drink huge amounts of booze without passing out or even getting dizzy at all, assuming that cytosine methylations responsible for tolerance are carried over to our offspring (sciency people pretty much agree on some of the methylations being transferred to our kids). This last bit might be bullshit though. Surely, only a tolerance to very few select substances are hardwired to our DNA.



I assume by 'memory', you're interpreting the word as a layman would, to mean recall of thought patterns in the CNS, right? I ask because it has a broader definition to neuroscientists and cellular biologists, and includes such phenomena as conditioned lowered depolarization thresholds in any or all cells. (Which is very relevant to a discussion of NMDA antagonists!)

The problem with your idea is that neurons don't divide, and even more importantly, don't spawn gametes. Your idea would only work if the DNA methylation you mentioned not only involved neurons, but oocytes and spermatocytes as well. Also, the methylated DNA segments would probably code for different proteins in different cells.

That said, I'd be open to the (admittedly controversial) idea that over the millennia, different cultures have selected for and against tolerance to the effects of certain drugs (especially alcohol), due to different survival pressures. But this just involves people who from birth are less (or more) susceptible to the drug's adverse effects having greater opportunities to have children. It wouldn't be affected at the genetic level by an individual's drug-taking behavior in one lifetime. But we're getting way off topic here.


----------



## crOOk

MyDoorsAreOpen said:


> I assume by 'memory', you're interpreting the word as a layman would, to mean recall of thought patterns in the CNS, right? I ask because it has a broader definition to neuroscientists and cellular biologists, and includes such phenomena as conditioned lowered depolarization thresholds in any or all cells. (Which is very relevant to a discussion of NMDA antagonists!)
> 
> The problem with your idea is that neurons don't divide, and even more importantly, don't spawn gametes. Your idea would only work if the DNA methylation you mentioned not only involved neurons, but oocytes and spermatocytes as well. Also, the methylated DNA segments would probably code for different proteins in different cells.
> 
> That said, I'd be open to the (admittedly controversial) idea that over the millennia, different cultures have selected for and against tolerance to the effects of certain drugs (especially alcohol), due to different survival pressures. But this just involves people who from birth are less (or more) susceptible to the drug's adverse effects having greater opportunities to have children. It wouldn't be affected at the genetic level by an individual's drug-taking behavior in one lifetime. But we're getting way off topic here.


A) No, my understanding of memory represents the broad definition :D 

B) Of course it's bullshit. Actually I was the one mentioning today in lecture that the deduction of behaviour possibly being handed down to our children is very far fetched considering there'd have to be a transfer of information (i use the very wide thermodynamic meaning of that word btw ;P) between cell in question and sperm cell or ovum.
Then again, even that is not completely true cause even those cells will be subject to some experience and might adapt through 5-Cytosine methylation as well.

Anyway, thanks for mentioning that our nerve cells don't divide, that was one very useful bit of information. Obviously, I had a hard time demonstrating the character of that last paragraph as it was the case so many times before even when I explicitely marked sentences and posts with the official sign for irony (a vertically mirrored "?"). I oughta delete it altogether lol. It's pretty obvious though that the memory acquired by a large number of neurons is unlikely to be implemented into one single DNA though. Or so I thought. I'm a tad drunkj, excuse me.



Anyway, having read that post and having pointed out all possible errors, you are not the least bit surprised by the idea of NMDA antagonists interfering with memory (again, the broad definition as it should've been perfectly clear already from above post) through demethylation of cytosine in calcineurin transcription enhancing areas?

Fear kept up through our cells' DNA? Not impressed eh?

Cause to me, this is quite astonishing and even the possibility of NMDA antagonists tolerance lowering properties having a common mechanism of action sounds like big fucking news to me. A neuronal reset switch through blockade of NMDA receptors.

I mean if I had any interest in this topic whatsoever, I'd have much better things to do than tearing apart a lame joke that was badly brought across.

EDIT: Lol seeing the lack of impression in you, I'm starting to sense that you only read the last paragraph of my post and decided to delete it altogether. :D

EDIT2: Rereading your post again while trying to find out why you completely ignored the actual posted information and instead selectively tore apart the last bit that contained no relevant information and seeing your mention of "lowered depolarization thresholds" being very important in understanding the effects of nmda antagonists in the same paragraph (this was the same paragraph in which you called me layman btw), then remembering you wrote a paper about it in med school, I finally came to realize what's wrong:
This information is completely new to you and wasn't included in your paper. So you're either rejecting the idea of nmda antagonists triggering a demethylation process of calcineurin gene enhancers cause you really do think it's highly unlikely the case or you're trying to discredit it since it poses a threat to the validity of your own findings! Either way, it's a typical behaviour often seen in academic narcissists, many of those being uni professors spending their time discrediting promising work of actual researchers to sucessfully earn fame among their easily impressed students. ;P Or maybe I'm just being paranoid, you were too lazy to read the whole post and I am overestimating the gravity of the above linked publication.


----------



## Solide

Damn, this is a very interesting topic even if some of this goes a little over my head. Next semester we're getting classes that I think cover the basics of things like this so might as wel read up a little on NMDA receptors and related shit already


----------



## crOOk

Solide said:


> Damn, this is a very interesting topic even if some of this goes a little over my head. Next semester we're getting classes that I think cover the basics of things like this so might as wel read up a little on NMDA receptors and related shit already


It's definitely a bit over my head as well Solide. As MyDoorsAreOpen has so precisely pointed out in his last post, I'm nothing more than a layman who by chance started studying medicine 3months ago. 7yrs out of school, no biology since 9th grade (last had an F), awful chemistry teacher back then... Not the best situation to work your way into neurophysiology, pharmacology and molecular biology.

I can tell you though it's nothing that you wouldn't have access to. While the lextures sure helped, they supplied nothing that I couldn't have tought myself through books in these 3 months (mind you, 3/4 of the time was spent dissecting a corpse and reading Clemente's Gray's Anatomy (1985)).

So if you are interested, don't make the same mistakes that I've been continuously making since I was 15 yrs old and assume that the topic is inaccessible. You can easily teach yourself all the basics in notime if you feel attracted to them.

So I'll try to give you a few recommendations how to start:
-Principles of chemistry: Anatomy of the atom; Orbital theory; tendencies is the periodic system; Types of connections between molecules; ph and acid-base reactions, ph buffer solutions; redox-reactions
-Organic chemistry: Features of carbon - apply orbital theory to this and make sure you understand the 3-dimensional character of a carbon atom that forms 4 covalent bonds; Hydrocarbons and the functional groups attached to them; cyclic hydrocarbons; aromatic qualities of cyclic hydrocarbons and heterocyclic molecules; Structure of various organic molecules; types of reactions that hydrocarbons are part of - electrophile subsitution, nucleophile substitution sn1 and sn2, radicalic substitution; repeat types of organic molecules and functional groups and the whole last bit over and over till you got a grip on it.

-Anatomy/Biology: You can skip that for the most part. Might wanna keep a good book for each at hand for whenever questions occur

-Biochem: Get started! A great book I'd recommend: "Lehninger Principles of Biochemistry, Fifth Edition" by Cox (lol) and Nelson; it's huge, don't be scared, the size and detail of the book will only help you opposed to a short book that covers almost all the same things in less detail; the body (un?)fortunately won't become less complex by reading simple literature. I got a link to the 5th ed as pdf so you can check it out before deciding whether you're gonna buy it or not.

I'm sure you'll absolutely love it. Good luck with getting familiar with the whole thing, it's really not as bad as it all sounds. Oh and before I forget, imho the basic principles of thermodynamics are very useful to know. The sooner the better, cause it'll probably take years till you really feel what Gibbs claimed in his days and you can apply that to any process we witness which will help you to a deeper understanding.

Regarding the above list: I can't guarantee for completeness, so anyone should feel free to add things. I also translated everything from German to english, since I'm mostly studying in German some of the things might be translated incorrectly. Just correct me if that's the case, I'll change the post. I'll also try to work on this biochem thread once I feel more secure with the whole topic.

peace


----------



## negrogesic

Becareful with psychopharmacology text books, the current ones used in med-school (USA) are antiquated, and while the fundamental information is good, it is simply full of errors, omissions, etc. I recently befriended the director of the NIH, and have expressed to him some of my concerns regarding the frightening lack of psychopharmacology in current US med-school curriculum. 

Unfortunately, the easiest, shortest residency, and least competitive specialty is generally speaking, Psychiatry. There is very little competition for this; unless you are at the top of your field, Psychiatrists are paid little, looked down on by many other M.D's/D.O.'s, and are generally not high ranking students. There are some definite exceptions, particularly those who take on multiple specialties, such as neurology etc. The sub-specialties within psychiatry are almost a joke, there are plenty of inept psychiatrists with 4,5 or even 6 sub-specialties (geriatric, forensic, liason, addiction, CAD etc, etc).

I am of the opinion that the standard must be set higher for psychiatrists, perhaps a mandatory PhD in psychopharmacology. Dermatological specialties (a pretty hot specialty right now due to high pay) are far more competitive, and I find most dermatologists - especially those who are also board certified dermatopathologists -know far more about psychopharmacology than the psychiatrists who are prescribing the heavily marketed medications pushed by savy drug-reps. Even more frightening, there has been an explosion in the number of psychiatrists obtaining the DATA waiver to prescribe Buprenorphine for opioid addiction, solely by taking an 8 hour online course. If curious, I will post the questions for the version I took; it is a fucking joke. In the meantime, these clueless psychiatrists are making a killing prescribing these C-III's without fear of provoking the DEA, yet are often by no means specialist in addiction medicine. 

Sorry about the psychiatry rant, I just find it to a festering sore in our medical system. Fortunately, I made the scramble into a ACGME-accredited school; I was originally planning on simply getting the M.D., but at this stage, I might as well get the D.O. in anesthesiology  (perioperative medicine), although the residency and fellowship commitments are steep. In my area, it is easy for a good anesthesiologist to make 45-50k a month for "comparatively" less time than other D.O's. Obviously, when you add on to that a pain management practice, the numbers increase significantly. Still, anyway you look at it, it is quite a bit a work, and not nearly as lucrative as finance (my actual "bread and butter")..........I've let this medicine get out of control, but I must say, I have a knack for anesthesia, but i've had extensive veterinary practice since the age of 17!         

Sorry for the rant, going on 50 hours without sleep.......


----------



## crOOk

negrogesic said:


> Becareful with psychopharmacology text books, the current ones used in med-school (USA) are antiquated, and while the fundamental information is good, it is simply full of errors, omissions, etc. I recently befriended the director of the NIH, and have expressed to him some of my concerns regarding the frightening lack of psychopharmacology in current US med-school curriculum.
> 
> Unfortunately, the easiest, shortest residency, and least competitive specialty is generally speaking, Psychiatry. There is very little competition for this; unless you are at the top of your field, Psychiatrists are paid little, looked down on by many other M.D's/D.O.'s, and are generally not high ranking students. There are some definite exceptions, particularly those who take on multiple specialties, such as neurology etc. The sub-specialties within psychiatry are almost a joke, there are plenty of inept psychiatrists with 4,5 or even 6 sub-specialties (geriatric, forensic, liason, addiction, CAD etc, etc).
> 
> I am of the opinion that the standard must be set higher for psychiatrists, perhaps a mandatory PhD in psychopharmacology. Dermatological specialties (a pretty hot specialty right now due to high pay) are far more competitive, and I find most dermatologists - especially those who are also board certified dermatopathologists -know far more about psychopharmacology than the psychiatrists who are prescribing the heavily marketed medications pushed by savy drug-reps. Even more frightening, there has been an explosion in the number of psychiatrists obtaining the DATA waiver to prescribe Buprenorphine for opioid addiction, solely by taking an 8 hour online course. If curious, I will post the questions for the version I took; it is a fucking joke. In the meantime, these clueless psychiatrists are making a killing prescribing these C-III's without fear of provoking the DEA, yet are often by no means specialist in addiction medicine.
> 
> Sorry about the psychiatry rant, I just find it to a festering sore in our medical system. Fortunately, I made the scramble into a ACGME-accredited school; I was originally planning on simply getting the M.D., but at this stage, I might as well get the D.O. in anesthesiology  (perioperative medicine), although the residency and fellowship commitments are steep. In my area, it is easy for a good anesthesiologist to make 45-50k a month for "comparatively" less time than other D.O's. Obviously, when you add on to that a pain management practice, the numbers increase significantly. Still, anyway you look at it, it is quite a bit a work, and not nearly as lucrative as finance (my actual "bread and butter")..........I've let this medicine get out of control, but I must say, I have a knack for anesthesia, but i've had extensive veterinary practice since the age of 17!
> 
> Sorry for the rant, going on 50 hours without sleep.......


Amphetamine ftw eh?


----------



## Solide

crOOk said:


> It's definitely a bit over my head as well Solide. As MyDoorsAreOpen has so precisely pointed out in his last post, I'm nothing more than a layman who by chance started studying medicine 3months ago. 7yrs out of school, no biology since 9th grade (last had an F), awful chemistry teacher back then... Not the best situation to work your way into neurophysiology, pharmacology and molecular biology.
> 
> I can tell you though it's nothing that you wouldn't have access to. While the lextures sure helped, they supplied nothing that I couldn't have tought myself through books in these 3 months (mind you, 3/4 of the time was spent dissecting a corpse and reading Clemente's Gray's Anatomy (1985)).
> 
> So if you are interested, don't make the same mistakes that I've been continuously making since I was 15 yrs old and assume that the topic is inaccessible. You can easily teach yourself all the basics in notime if you feel attracted to them.
> 
> So I'll try to give you a few recommendations how to start:
> -Principles of chemistry: Anatomy of the atom; Orbital theory; tendencies is the periodic system; Types of connections between molecules; ph and acid-base reactions, ph buffer solutions; redox-reactions
> -Organic chemistry: Features of carbon - apply orbital theory to this and make sure you understand the 3-dimensional character of a carbon atom that forms 4 covalent bonds; Hydrocarbons and the functional groups attached to them; cyclic hydrocarbons; aromatic qualities of cyclic hydrocarbons and heterocyclic molecules; Structure of various organic molecules; types of reactions that hydrocarbons are part of - electrophile subsitution, nucleophile substitution sn1 and sn2, radicalic substitution; repeat types of organic molecules and functional groups and the whole last bit over and over till you got a grip on it.
> 
> -Anatomy/Biology: You can skip that for the most part. Might wanna keep a good book for each at hand for whenever questions occur
> 
> -Biochem: Get started! A great book I'd recommend: "Lehninger Principles of Biochemistry, Fifth Edition" by Cox (lol) and Nelson; it's huge, don't be scared, the size and detail of the book will only help you opposed to a short book that covers almost all the same things in less detail; the body (un?)fortunately won't become less complex by reading simple literature. I got a link to the 5th ed as pdf so you can check it out before deciding whether you're gonna buy it or not.
> 
> I'm sure you'll absolutely love it. Good luck with getting familiar with the whole thing, it's really not as bad as it all sounds. Oh and before I forget, imho the basic principles of thermodynamics are very useful to know. The sooner the better, cause it'll probably take years till you really feel what Gibbs claimed in his days and you can apply that to any process we witness which will help you to a deeper understanding.
> 
> Regarding the above list: I can't guarantee for completeness, so anyone should feel free to add things. I also translated everything from German to english, since I'm mostly studying in German some of the things might be translated incorrectly. Just correct me if that's the case, I'll change the post. I'll also try to work on this biochem thread once I feel more secure with the whole topic.
> 
> peace



Hey man, thanks for the reccomendations and effort! Tho I feel I should've been a little more clear :D

I'm studying pharmaceutical sciences (second year now) and by 'basics of things like this' I implied the basics of pharmacological stuff. I've already passed principles of chemistry and organic chemistry and some basic biochemistry courses. Next semester i'm having courses such as 'medicinal chemistry' which are more geared towards pharmacology specifically.

I've looked through that pdf and it looks like a good, not to complex book, but most of it looked pretty familiar (in fact, I saw a couple of things which I'm studying right now for an exam tomorrow )

Also, to be contributing a little to this topic: I'm prescribed Ritalin and the last few weeks my tolerance has gone up quite a bit. I've been supplementing with magnesium a little, but tomorrow I'm going to add a little bit of DXM everyday and see how that affects tolerance.


----------



## MyDoorsAreOpen

negrogesic said:


> Becareful with psychopharmacology text books, the current ones used in med-school (USA) are antiquated, and while the fundamental information is good, it is simply full of errors, omissions, etc. I recently befriended the director of the NIH, and have expressed to him some of my concerns regarding the frightening lack of psychopharmacology in current US med-school curriculum.



True. We only got a whirlwind tour of it in my first 2 years. I've learned more about psychopharmacology from BL than I did in med school, no fooling.



			
				negrogesic said:
			
		

> Unfortunately, the easiest, shortest residency, and least competitive specialty is generally speaking, Psychiatry. There is very little competition for this; unless you are at the top of your field, Psychiatrists are paid little, looked down on by many other M.D's/D.O.'s, and are generally not high ranking students. There are some definite exceptions, particularly those who take on multiple specialties, such as neurology etc. The sub-specialties within psychiatry are almost a joke, there are plenty of inept psychiatrists with 4,5 or even 6 sub-specialties (geriatric, forensic, liason, addiction, CAD etc, etc).



This problem is largely a part of the underfunding and neglect of mental health services in the US. Also, when you've got a patient base that's largely unemployable (and therefore poor), unpleasant to deal with, and that society stigmatizes, it shouldn't be any wonder that the bar gets lowered for attracting people to this line of work. I'm not anti-psychiatry at all. I think that the legally sanctioned use of most drugs and treatments that target the mind warrant the oversight of a well-trained physician, who understands the human body and how these tools affect it. But I agree with you that psychiatry needs to put the 'physic' back in 'physician' -- a good psychiatrist should know their pharmacology better than a pharmacist, and ought to be on their toes with the physiology of the entire body. (Because the things they prescribe don't just affect the brain!)


----------



## Dunno

Don't have time to read through all the posts but saw someone mentioned dxm reversing benzo tolerance & people using it for withdrawals or to stop withdrawals?? Does this work & what is the recommended dosage?


----------



## MeDieViL

Dunno said:


> Don't have time to read through all the posts but saw someone mentioned dxm reversing benzo tolerance & people using it for withdrawals or to stop withdrawals?? Does this work & what is the recommended dosage?



It seems to work well for those that are trying it, 60mg twice a day.


----------



## Dunno

MeDieViL said:


> It seems to work well for those that are trying it, 60mg twice a day.



60mg twice a day with usual dose of alprazolam?


----------



## MeDieViL

Dunno said:


> 60mg twice a day with usual dose of alprazolam?



Yeah, tolerance should start decreasing then after wich youll need to reduce the dose a bit everytime.


----------



## Dunno

Cool thanks i will give it a go as i'm trying to reduce my dosage and hopefully get off these stupid things.

So 120mg of DXM a day?


----------



## MeDieViL

Cool, keep us updated.


----------



## MeDieViL

Dunno said:


> Cool thanks i will give it a go as i'm trying to reduce my dosage and hopefully get off these stupid things.
> 
> So 120mg of DXM a day?



Yes, take 2 doses of 60mg


----------



## Dunno

Ok, thanks alot


----------



## Dunno

I know everyone is different but just on average how many days would it take for it to lower tolerance?


----------



## MeDieViL

A couple more reports.



> I have been using dxm with oxy in a taper to help. Usually in wd I'm so god damn lathargic I get nothing done at all. The dxm stimulates me to the point of being normal if not better than.
> 
> In the morning on my way to work ill dose with dxm and somehow not have any wd symptoms. I'm hoping to taper down to at least 20mg before CT and then use dxm for a couple days. Ill be sure to report back.





> This works for me really well.
> 
> The only problem is getting that much DXM, as I get mine from the pharm. Extracting that much is pretty annoying.
> WHen im tripped out on DXM the bodily aspect of the withdrawals still seem to be there but I just dont give a damn. It sure dosnt help me sleep but it's wayy better than tossing around, sweating like hell and feeling depressed and shit. When I get a high enough dose, usually around 800-900 twice a day, 3 days of nasty wds go by soo fast.
> It helps tremendously with the depression aspect of the wds too, cuz for me I get alot of motion and music euphoria from DXM, so listening to loud music + jogging = me happy. Almost makes me want to go to a rave. So basically after two to three days of heavy DXM therapy Im pretty much back to normal.
> 
> I love DXM!





> Hi all,
> 
> After some serious problems with Oxy and Bupe, im free from opiates. it was kinda simple in the end. from 300-800mg oxy most days, then 10mg bupe day 1 with 500mg Dxm (it was a bad day) and 2mg xanax. Next day 2mg bupe plus 1000mg dxm. days 3,4,5 with 2mg Bupe 1500mg of DXM and 2mg Xanax. Day 6, 7 1000mg dxm and no bupe, xanax to taste with only 10 left. finished the rest of the DXM off (started with 25 500mg capsules) and the xanax over 7 days and then nothing. 1st night no sleep and desperate for something, but defenitely no sickness, no throwing up. Writing and drawing (things i dont normally do) helped thru the bad parts.
> 
> ]
> does anyone else have good experience in this way? I found theres no withdrawal (for me at least) no matter how high you go, just boredom when the closed eye visuals stop


same guy:


> totally this works for me so well its almost too easy. the first days always gonna be unsettling but the DXM makes it very introspective and instead of watching the clock and 10 mins seeming to take forever to go by, the time goes quick and can generally be spent lying on the couch and watching cool patterns and visions form behind your eyes. (of course they dissappear if you take too much xanax.) i used this before to get off methadone, without suboxone about 5 years back. generally once you know the amount of dxm you can take without flipping out but enjoying the effects, you can settle on that dose about twice a day. that could be as little as 200mg in the past, but there is an effect that causes the neurons to protect themselves (possibily to prevent Olneys lesionss) and after a while dxm becomes ineffective in some of the more fun ways or you gotta dose up more. Ive never found one withdrawal symptom from this drug except boredom, even for months at a time daily dosing. tho it will make you slurr your speech and look really messed up. And its actually not that hard to get in an easy to take form, if you do your research. (no sluggin back bottles of cough syrup needed)
> 
> i find that the effects resemble ketamine in the peak, and there is known to be cross tolerance from ketamine. Defenitely it feels like your body is anaesthetized and your legs get that oh so sweet relief, no restless legs. In the end its just what ive found out for me over the last ten years. be happy to share more on it



Ket for GBL withdrawals:


> ^ I disagree. Works absolute wonders for me. Admittedly I have fairly minor G w/d anyway but ketamine kicks any w/d from anything I've ever come across to one side so far. Kinda like insta-ibogaine only cheaper and easier to get hold of.


----------



## MeDieViL

Dunno said:


> I know everyone is different but just on average how many days would it take for it to lower tolerance?



You should definatly see results within a week.


----------



## MeDieViL

crOOk said:


> Seems to work fine, tolerance has levelled out, I'm at a slightly lower amp dose than I was when I started, while before that tolerance was constantly increasing. I'm taking 30-60mg DXM 1-3times per week so far, along with my amp dose and a fat dose of Magnesium (eyeballed).
> 
> The following is an article from 2001, so it's not really up-to-date, but still offers some help in understanding the mechanism of nmda-antagonists antidepressant effects and possibly their tolerance decreasing effects as well.
> 
> 
> In short: There are 3 genes that are highly expressed (suggesting they contribute to the developement of those neurons) in developing neurons of the newborn's brain. These genes are downregulated by NMDA receptor activity!
> 
> While two of these 3 genes were unknown when this was published, the third seems to be the equivalent to a gene found in yeast, that is responsible for inducing the G0 phase of cells. G0 is the phase were cells will not devide themselves any further.
> 
> It still doesn't make sense to me, but this sure is helpful.
> 
> On another note: Ethanol use seems to have an upregulating influence on NR2b gene transcription. An epigenetic mechanism is suggested here.
> Booze->More NMDA 2b receptors
> 
> Btw looking at how I've developed a form of tolerance to some drugs, specifically dissociatives and psychedelics, these were much more persistant, less quickly reversible than say pot tolerance. Epigenetic mechanisms?
> 
> The epigenetic mechanisms referred to are, you've probably guessed it, methylation and demethylation of CpG sites in the regulatory areas of the mentioned gene. (Methylation of C5 in Cytosine; CpG=Cytidine+phosphate+Guanosin, one of the sequences in our dna/rna; Regions that enhance or silence expression of a gene are usually very rich in these CG-sequences and methylation of Cytosine in position 5 is thought to block these enhancing or silencing function by preventing the responsible specific transcription activators to bind to them).
> 
> And indeed it could be shown that booze induced demethylation of these areas, thereby enabling increased occupation of these DNA-binding sites and in consequence increased transcription of the NR2b gen, leading to  higher density of NMDA 2b receptors.
> 
> Here's the publication:
> 
> I think this one is free. For the other one feel free to write me.
> http://tinyurl.com/mightbefreedontknow


Interesting post


----------



## Dunno

^^Shit, looks like they took massive doses of DXM though. Would it still do anything at 120mg a day? Day 2 so far

I really hope this works..My DXM trippin days are over doesn't effect me anymore but even two cups of 10mls which equals 60mgs tastes like shit!!!!!!!!!! I'd hate to drink 1000mgs fuck!!! LOL!!


----------



## MeDieViL

Dunno said:


> ^^Shit, looks like they took massive doses of DXM though. Would it still do anything at 120mg a day? Day 2 so far
> 
> I really hope this works..My DXM trippin days are over doesn't effect me anymore but even two cups of 10mls which equals 60mgs tastes like shit!!!!!!!!!! I'd hate to drink 1000mgs fuck!!! LOL!!



Mate, most ppl here tried those doses and it worked for them, give it a try


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## Dunno

man your joking right? 1000mgs DXM? That's like a bottle & 4 quarters


----------



## MeDieViL

Dunno said:


> man your joking right? 1000mgs DXM? That's like a bottle & 4 quarters



No no, i ment that most ppl here take 60mg twice a day lol.


----------



## Dunno

Lol ok yeah 2nd day today, ill keep updated


----------



## Dunno

From Erowid: 

DXM, as well as other dissociatives, seems to prevent and even reverse tolerance to (and thus physical addiction to) many drugs. In the case of opiates, DXM has been used to treat withdrawal symptoms (169). DXM plus diazepam (ValiumTM) was tested and found to be more effective at combating the symptoms of heroin withdrawal (goose flesh, tremors, pupil dilation, joint pains, etc.) than chlorpromazine (ThorazineTM) plus diazepam (34). A further study verified this and found that adding tizanidine (an alpha-2 adrenergic agonist) to the DXM+diazepam cocktail was even more effective (133).

Dissociatives have also been found to reverse or prevent tolerance to cocaine (247), nicotine (249), and alcohol (232), and some researchers have suggested that DXM (and other NMDA antagonists) may be universally useful in most if not all drug addictions.


----------



## MeDieViL

Its a shame really they arent included the standard drug addiction treatments. Tolerance and withdrawals are the basic foundation of drug addiction.


----------



## Dunno

True, well i have a high tolerance to xanax & have for around six years so hoping this works. Can't see it happening but see what happens


----------



## MeDieViL

Dunno said:


> True, well i have a high tolerance to xanax & have for around six years so hoping this works. Can't see it happening but see what happens



I hope it will for ya too, keep us updated on this one mate!


----------



## Dunno

Just can't see how it would work while i'm still taking xanax


----------



## MeDieViL

Check out those experiences, those are all that tried it meaning it so far consistently worked for everyone, no mixed reports wich make it look extremely interesting:


> Well I am down 50% on my valium now but its not comfortable - I may have to go back up or increase the memantine or add Delsym or something.
> 
> I get the distinct impression that DXM is more effective for benzos than memantine is but at the same time, I was taking 60mg of Delsym twice a day versus taking 20mg of memantine twice a day so maybe I just need to go up in the mem dose.
> 
> Personally, I think Delsym was working quite well with the valium withdrawal though - my tolerance to it was going down when I was on the Delsym and it started on the second or third day... I switched to memantine due to concerns about drug interactions with DXM but I may switch back because memantine has suppressed my breathing when I take too much (up to 60mg a day) and doesn't appear to be working as well as DXM does. Plus I quit taking drugs altogether in order to do my taper as quickly as possible and get back to work.
> 
> Can anyone comment on how well DXM works versus memantine for benzo withdrawal? I would imagine that it is superior - I remember that my valium tolerance dropped on its own when I was doing the Delsym whereas the memantine seems to just reduce the withdrawal symptoms (ie., no brain fog, no memory problems, still functional, no panic attacks, but still psychological symptoms like feeling that your heart is going to give out, weird body feelings, but nothing physical to back it up other than random pains).
> 
> It seems to be somewhat commonly reported that for whatever reason, DXM users can keep using the drug they are tolerant to and still experience a tolerance reduction but this does not seem to be the case with memantine.
> 
> I guess I may have to just suck it up and switch to the syrup and just make sure to avoid serotonergic drugs, although I wonder how much damage a roll would do with therapeutic levels of Delsym - I won't be trying it though.





> I tend to have any adverse reaction that is clinically possible - my body really dislikes pharmaceutical drugs so don't take my word as the final word, it was more a word of caution - but cardiac events do appear to be a problem with memantine.
> 
> I switched to DXM starting last night by taking 5mL of Delsym at midnight. I then SKIPPED my Valium dose and took another 5mL at 6AM then fell asleep about 11AM. I woke up about 3PM, which meant I missed my afternoon dose of Valium as well and then about 4:30 I finally took 5mg of Valium and that's all I've had today. I took another 5mL of Delsym when I woke up and another 5mL at 7:30 or so and will take another 5mL at midnight. Normally I'd have taken 20mg of Valium in this time period so there is definitely something to dextromethorphan versus memantine. I should also note that I have experienced no respiratory suppression or heart abnormalities since I stopped taking the memantine, even with the extreme decrease in Valium.
> 
> Even more amazing is the fact that when all this went on with the heart racing out of control on the MDMA/Mescaline combo and the drinking that ensued, I ended up taking a full extra 20mg of Valium that day but I'm still able to come down so quickly off of it the day after the fact.
> 
> As for the tolerance prevention, just go back on the memantine after you come down from the MDMA. Memantine has quite a long half-life though so there's still a chance that a good bit of it could be in your system even a week later. Even at the low side of 60 hours, that's 2.5 days before your blood level of memantine is halved and another 2.5 days before its quartered, meaning that it takes 5 days to get down to 10mg plasma levels after taking 40mg. On the high end, the half life is 100 hours so you'd be looking at just over 4 days before your plasma levels would hit 20mg after dosing 40mg.
> 
> Either way, it seems that all of the NMDA antagonists have the ability to cause severe CNS issues including respiratory failure, heart attack, and stroke, so just be careful with them. Ketamine has been known to cause significant increases in pulse and blood pressure and everyone knows that recreational levels of dextromethorphan cause tachycardia and hypertension.
> 
> All that being said, the 120mg of dextromethorphan polisterex I have taken is having less of an impact on my pulse and blood pressure than 40mg of memantine did.





> I took Alprazolam for 3 years, then went through accidental cold-turkey withdrawal because the local pharmacies weren't carrying any (happens where I live occasionally, sucky country/city). I experienced severe withdrawal symptoms including paranoia and transient psychosis but soon I got again on Alprazolam and thankfully didn't have a seizure. During that period I was completely tolerant to 2 mg Alprazolam's both sedative and anxiolytic effects.
> 
> Since I started taking Memantine, the tolerance was reversed somewhat and 1 mg was anxiolytic and practical enough for social anxiety disorder. 2 mg was very effective sedative. Tolerance didn't develop any further from this point on.
> 
> When I began tapering off Alprazolam for good, I was on 2 mg/day and the withdrawal was pretty negligible, only symptoms were irritability and slight sense of panicking, despite the rapid taper process.





> I'm totally getting similar results from Huperazine A. I've been taking 100 mcg twice daily for 4 days. I wonder if anyone else can relate to this w/r/t huperazine.
> 
> In case it's of interest to you, I've cut my alprazolam consumption in half. Not because I'm trying to give it up but because it's suddenly too potent. FWIW I have a 6-year daily alprazolam habit.



The experiences need to keep coming it, and the addition of DXM doesnt need much efford, so not much reason not to try it.


----------



## Dunno

Have read those but how would it work while still taking a benzo?


----------



## MeDieViL

Dunno said:


> Have read those but how would it work while still taking a benzo?



They induce upregulation and seem to reverse the changes induced by tolerance/dependency.


----------



## Dunno

I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol


----------



## MeDieViL

Dunno said:


> I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol



Well, you may be the one convincing people that still think the same about this right now


----------



## MeDieViL

I just came acros this post:


> Originally Posted by caseface99
> ^^ Not to mention doesn't DXM help dampen tolerance from increasing?
> That's the theory but several of us tried a lengthy experiment to test this and didn't get very impressive results... not that's its scientific but I haven't met anyone on here who has tried this over a substantial amount of time while using a lot and can definitely say "this greatly slowed tolerance acquisition" let alone reversed any.


http://www.bluelight.ru/vb/showthread.php?t=543949

I'm posting this to encourage those not getting as positive results to report their experience too.

He's experience did not an increase in tolerance tough, just that dxm didnt reverse he's tolerance:


> I had been taking opioids for years for pain but I was taking very consistent doses that hadn't changed substantially after 2+ years of use at that time. I was taking 60mg DXM Hbr TID when I was doing it but I don't think my worthless results imply much if anything to people looking to use DXM to attenuate tolerance acquisition associated with recreational use.
> 
> My tolerance wasn't rising so I was hoping that I could reduce my tolerance some so when I say it was worthless THIS is what I mean. At the time main were theorizing that it could be used to REVERSE tolerance some and not just slow the development.


----------



## Dunno

Ok, thanks for those posts. I'll see how it goes in a few days


----------



## Transform

Dunno said:


> I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol



The brain is an incredibly complex system, and we still don't fully understand it, however, what we can do is use science to help predict what will happen when we make a particular change, based on past experience.

Past experience in this case shows that 100% of the time, DXM will reduce tolerance even when taken with the substance of abuse.

Funny thing is, we do understand this mechanism fairly well, and if you read the journals in this thread you'll hopefully be able to understand why.

Good luck to you.


----------



## MeDieViL

How the hell can i get this thing more popular so more people try it? I first posted it in other drugs thinking a ton of ppl will try it as they have major tolerance issues there, i got 2 comments saying good work and none tried it to my suprise, after it got moved to ADD then people started trying it however considering the succes ppl have been having far more people should try it, if poeple keep having succes eventually i would like to get this thing to become the basic first thing poeple try when fighting drug tolerance or addiction.


----------



## MeDieViL

Another thing NMDA antagonists have potential for is turning certain addictive meds into sustainable long term treatments for mental disorders such as opiates and amphetamine's, normally they cant be used for that since tolerance will occur rapidly, however it may just be easier to counteract those issues rather then coming up with new novel compounds.

I like the quote someone put here before, NMDA antagonists certainly arent the magic bullets, however they are the next best thing after the magic bullets.


----------



## amanitadine

^^^ I took part in a study years ago measuring the NMDA antagonistic effects of the separate isomers of methadone. This is the primary reason methadone tolerance does not skyrocket like traditional agonists.....

Great work by the way, makes for fascinating reading.

Separate but similar study:


*The d- and l- isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord*

A. Laurel Gorman, Kathryn J. Elliott and Charles E. Inturrisi*
Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA
Received 3 December 1996; revised 7 January 1997; accepted 7 January 1997. Available online 28 January 1998. 
Abstract
Racemic (dl)-methadone has antagonist activity at the N-methyl-D

-aspartate (NMDA) receptor. We evaluated dl-methadone, the opioid active (l-) and the opioid inactive (d-) isomers in competition binding assays. dl-Methadone and its d- and l- isomers exhibited low micromolar affinities for the [3H]MK-801-labeled non-competitive site of the NMDA receptor in both rat forebrain and spinal cord synaptic membranes, with Ki values and displacement curves similar to those of dextromethorphan, an established NMDA receptor antagonist. They lacked affinity at the [3H]CGS-19755-labeled competitive site of the NMDA receptor. Therefore, both methadone and its the d- and l- isomers differ from morphine, hydromorphone, and naltrexone in that they have non-competitive antagonist activity at the NMDA receptor. A non-opioid NMDA receptor antagonist, such as d-methadone, may improve the efficacy of morphine by attenuating the development of tolerance.


----------



## Transform

MeDieViL said:


> How the hell can i get this thing more popular so more people try it? I first posted it in other drugs thinking a ton of ppl will try it as they have major tolerance issues there, i got 2 comments saying good work and none tried it to my suprise, after it got moved to ADD then people started trying it however considering the succes ppl have been having far more people should try it, if poeple keep having succes eventually i would like to get this thing to become the basic first thing poeple try when fighting drug tolerance or addiction.



I've been sending people here from from EADD when I think they could use the advice, but I think the movement to ADD in some ways highlights the problem. This thread is full of excellent evidence, studies and journal pages, but non ADD'ers don't want/have time to read and understand all of the evidence, they want to read a single page with a brief summary, what they need to do, and an FAQ.
 They're quite happy to trust us to have read the studies properly, they just need to know what to do. It's often a shame, but most people will trust scientists pretty blindly.

Write up the key points here into layman's terms, have it stickied in the dark side, and water liberally, pruning in spring.


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## avcpl

I really want to try, but I just can't adapt. After just three days of memantine (5, 10, 15mg), I had to stop due to side effects. I'll give dxm a try after I stop my saint john's wort, but seriously doubt I'll be able to get to the levels required to reverse tolerance...


----------



## M Brace

I too would like to try this for MDMA tolerance, but I'd like to learn more about the safety of taking dxm within even one day's proximity of MDMA.  The memantine heart issues are also of concern. That said, I've been very interested in this thread.  Keep it going!


----------



## avcpl

MeDieViL said:


> Yes the benefit should remain after the NMDA antagonist has been withdrawn as they upregulate a bunch of receptors implicated in drug reward, atleast thats how it looks in theory, ketamine after mdma also abolishes the crash for most, indicating it just upregulates receptors again that have been downregulated by MDMA.



Mbrace, as MeDieViL stated above, that the NMDA antagonist benefit should remain, so would you really need to take the DXM so close to the MDMA? 

Maybe first try the DXM 60mg 2x/day for a week for tolerance reversal/upregulation and then wait a week (or more) before you roll?  

That's my plan (in between my trials of 6g/day of SJW, since it's not  good to combine the two), but I worry it will make me too lightheaded since I often use powertools or am up on a roof or driving and that might be too risky.

I should also add that on memantine, when I was exercising my heartrate was easily 15bpm higher than it normally is and was getting into an uncomfortable range...



.


----------



## Dunno

Rodent study's indicate that nmda antagonists prevents tolerance to the sedative effect, however another study showed that an NMDA antagonist did not prevent tolerance to the anxiolytic effects.

Hopefully it reverses the tolerance to the anxiolytic effects in humans otherwise there's no point. 4th Day so far, runnin low, time to buy a new bottle tomorrow lol


----------



## OpiYum

just want to share my story. was iv heroin user for 5 years, opiates for 8.  tried suboxone and it didnt work and methadone i couldnt function.

now im off all opiates (including suboxone and dont have PAWS)

day1-day4 25%decrease per day on suboxone
day 4- 100mg rectal 4meoPCP
day 5- heroin (new years, cmon) and coke
day 6-8 quick taper off methadone
day 8 methoxetamine

done.
no w/d
feeling  pretty good.


----------



## FlippingTop

I shall read through this tonight when I have some time.

Fucking good work :D


----------



## Wizzle

I have used GHB quite excessively in the past and wonder if a NMDAR-agonist regimen might repair any possible damage. Also, I take 120 mg's of methylphenidate daily for adhd.. I have been doing so for about six months now and feel it is getting less effective. I am thinking about trying this but I'm not certain. All the NMDAr-agonists seem to have some serious setbacks. Also, the anecdotal reports provided by MeDieVil say that it's is probably not really effective for MPH tolerance..

I've never taken DXM but for some reason it rubs me the wrong way, can it be safely taken with my meds? I would use ket or nitrous but I don't want to get high, I haven't used any recreational drugs in a long time and I would like to keep it that way. Maybe I should get some Xenon 


edit: should I stop taking my meds while on dxm? I am thinking of taking 120 mg of dxm for ten days.. I can buy XR caps with 30 mgs and plan to take 2 in the morning, two at night.. I don't like the idea of not taking my meds though..


----------



## Transform

You needn't get high using ketamine, you're not supposed to feel the effect, and you can continue your medication while using DXM.


----------



## Wizzle

Okay, great. Are there any reports on methylphenidate tolerance and DXM or Ket?

Is it about total volume or what? Is one or the other more effective? I have a good source for cheap ketamine so it might be more price effective then dxm. A gram would cost me as much as a 10 day supply of dxm.. What would oral dosages be, and how effective is the first pass metabolite norketamine?

I just want to look at all the options.. taking for instance 50mg's of ket (oral!) a day seems less unhealthy and cheaper then taking 120mg's of dxm a day..


edit: I've looked for reports and couldn't find what I was looking for.


----------



## MeDieViL

Looks like youll be the first trying it for ritalin, they work for stims since they upregulate D2 and D3 in the striatum wich should also work for ritalin's tolerance, you can keep on taking the ritalin with the DXM altough a break with dxm only would likely work better to reverse an allready existing tolerance.

Keep us updated


----------



## MagickalKat777

Well I have felt it the past few days - the memantine levels finally dropped and I haven't been taking Delsym. I was experimenting to see if the withdrawals would come - and they did. I had to go back to 20mg of Valium yesterday and I've been having to take it earlier.

Back to Delsym tonight. I'm going to do a 180mg "attack" dose tonight before I take my night dose, then do another 180mg with my afternoon Valium dose, then go down to 120mg twice a day for a few days, then down to 60mg twice a day maybe on day 10.

Whoever says that its a placebo thing doesn't know what they're talking about at all - even my pharmacist knows about the use of dextromethorphan for opiate and benzo tolerance reduction. LOL!

Anyway, yeah, I feel like crap now that the memantine has bottomed out. Its about perfect timing too.

I'm glad to have that poison out of my system though. The respiratory suppression, weird pulse issues (sometimes stimulants increased my pulse a LOT more than usual, other times it decreased, once it stayed the same - hallucinogens, including shrooms, caused abrupt heart rate increases but I have since shroomed after I ceased the memantine and the issue is no longer there), and the really jacked up head feeling ---- not worth it. Delsym at the doses I take is more expensive than where I got my memantine but its more easily accessible and it doesn't cause any of the problems that PCP and memantine do with my cardiovascular system. Ketamine causes tachycardia but no respiratory suppression with me - and ketamine only tends to cause tachycardia when I quite simply just do too much.

Anyway, don't give up - Delsym and memantine are both extremely effective. To be honest, I would think that taking your full Delsym dose all at once instead of twice a day would probably still be quite effective as I've heard of successes with regular dextromethorphan taken only twice a day.


----------



## Dunno

^^^^^So your benzo tolerance dropped after taking DXM, also at what dose of DXM did you take & for how long? I have been taking 60mg twice a day with my Xanax. Today will be day 6 of taking DXM & Xanax


----------



## MagickalKat777

What form of DXM are you taking? The polisterex (Delsym) is what I've used. I was using 120mg twice a day when I first started taking it and by day 3, I knew I could cut my Valium dose because I'd take my full dose and pass out cold. That is pretty much the queue for me that its time to drop the dose a bit.

I honestly question whether or not standard DXM HBr will work as well or not - it gets metabolized into DXO much more rapidly than the polisterex formulation does. This is why a lot of people don't like tripping on Delsym. Even at double the dose of what they would normally take of an HBr formulation, they still never really get to the intense peak of the DXM experience and rather hit a plateau and stay there for a LONG time.


----------



## Dunno

Robitussin cough syrup


----------



## Dunno

MagickalKat777 said:


> What form of DXM are you taking? The polisterex (Delsym) is what I've used. I was using 120mg twice a day when I first started taking it and by day 3, I knew I could cut my Valium dose because I'd take my full dose and pass out cold. That is pretty much the queue for me that its time to drop the dose a bit.
> 
> I honestly question whether or not standard DXM HBr will work as well or not - it gets metabolized into DXO much more rapidly than the polisterex formulation does. This is why a lot of people don't like tripping on Delsym. Even at double the dose of what they would normally take of an HBr formulation, they still never really get to the intense peak of the DXM experience and rather hit a plateau and stay there for a LONG time.



So you took 120mg all up in one day or 240mg all up in one day?


----------



## MagickalKat777

I would switch to Delsym. Its more expensive but if you're doing regular Robitussin, you need to take 4-6 doses a day to try to maintain plasma levels and even then, I really think the DXO conversion just happens too fast.


----------



## MagickalKat777

Dunno said:


> So you took 120mg all up in one day or 240mg all up in one day?



I took 120mg twice a day. Didn't get any psychoactive effects to speak of if you're worried about that. It was overkill but I wanted to get my tolerance going down fast and I'm pretty familiar with the safety profile of DXM, having taken 800+mg of the HBr form at least 5 days a week for about a year and stopping with no issues during or after.


----------



## Dunno

I don't think it's available in Australia but i'll continue with Robitussin & keep people updated


----------



## Dunno

MagickalKat777 said:


> I took 120mg twice a day. Didn't get any psychoactive effects to speak of if you're worried about that. It was overkill but I wanted to get my tolerance going down fast and I'm pretty familiar with the safety profile of DXM, having taken 800+mg of the HBr form at least 5 days a week for about a year and stopping with no issues during or after.



That's alot of that shitty syrup but i'll give it a go


----------



## Dunno

Not worried, used to take it all the time then i lost the magic so gave up. Just want my Xanax tolerance to drop


----------



## MagickalKat777

I would do 60mg 4 times a day and see how that does for you. A higher dose still isn't really going to slow down the DXO conversion and elimination by much.

How many times a day do you take your Xanax? What I would do is take it with every Xanax dose you take at 30-60mg at a time. DXO definitely lasts longer than Xanax does so maybe if you can get a consistent blood level around the time you're actually taking the Xanax, it will work. I can't see regular DXM being effective for something like Klonopin or Valium but for Xanax and Ativan it should work if you dose at the same time you take your Xanax pills.


----------



## Dunno

MagickalKat777 said:


> I would do 60mg 4 times a day and see how that does for you. A higher dose still isn't really going to slow down the DXO conversion and elimination by much.
> 
> How many times a day do you take your Xanax? What I would do is take it with every Xanax dose you take at 30-60mg at a time. DXO definitely lasts longer than Xanax does so maybe if you can get a consistent blood level around the time you're actually taking the Xanax, it will work. I can't see regular DXM being effective for something like Klonopin or Valium but for Xanax and Ativan it should work if you dose at the same time you take your Xanax pills.



I take Xanax roughly three times a day. The last few days i've been able to keep to 6mg Xanax throughout the day. I will try lowering my Xanax dose tomorrow and see how i go.

I take 60mg DXM in the morning before i dose Xanax & about seven hours later take another 60mg DXM.

Also, has anyone experienced a reverse in their tolerance to the sedative effect only & not prevent tolerance to the anxiolytic effects?


----------



## Wizzle

MeDieViL said:


> Looks like youll be the first trying it for ritalin, they work for stims since they upregulate D2 and D3 in the striatum wich should also work for ritalin's tolerance, you can keep on taking the ritalin with the DXM altough a break with dxm only would likely work better to reverse an allready existing tolerance.
> 
> Keep us updated



Right, and the striatum is hypothesized to be involved in sustained and selective attention right? 

My tolerance has mostly occured in the sustained and selective attention area... hyperactive symptoms have also increased but not so much.. Impulsiveness seems to not have been affected, has been down ever since starting the meds.. I have read the research that MPH is not better then placebo after 25 weeks and it scares me because I'm starting to have the same old problems again..

So, what do you think... ket or dxm? ket would be taken orally so It'll actually be norketamine. I would consider memantine but a certain indian supplier doesn't ship to the Netherlands because of customs-problems. Stopping my meds is possible for about ten days so I have a window..

Also, the DXM I can get is sustained release, caps of 30 mg... Is there some need for High plasma levels? In that case I might do 90 mgs twice a day..


----------



## avcpl

MagickalKat777 said:


> I honestly question whether or not standard DXM HBr will work as well or not - it gets metabolized into DXO much more rapidly than the polisterex formulation does.



Which is more desireable though, since DXO is also listed as an "uncompetitive channel blocker", same as DXM is on this list of NMDA receptor antagonists: http://en.wikipedia.org/wiki/NMDA_receptor_antagonist

And, "dextrorphan is much more potent of an NMDA receptor antagonist and much weaker as a serotonin reuptake inhibitor in comparison": http://en.wikipedia.org/wiki/Dextrorphan

I'm not clear if what we're looking for are is to blast the neurons with repeated strong doses of potent NMDA antagonists, or sustained plasma levels, or if both are needed. (or do we really know and are just speculating?) 




.


----------



## ferinox

MeDieViL said:


> Another thing NMDA antagonists have potential for is turning certain addictive meds into sustainable long term treatments for mental disorders such as opiates and amphetamine's, normally they cant be used for that since tolerance will occur rapidly, however it may just be easier to counteract those issues rather then coming up with new novel compounds.
> 
> I like the quote someone put here before, NMDA antagonists certainly arent the magic bullets, however they are the next best thing after the magic bullets.



I'm pretty sure I remember reading that glutamate is heavily involved in fear extinction so maybe it's not a good treatment for anxiety. I still use opiates in combination with dxm to allow self medication with less unfortunate effects like tolerance and heavy dependence. Nothing treats my anxiety and depression so effectively. Eventually if I want my life to go anywhere, I might have to reconsider this method of treatment. If only I had adequate money, I could medicate and go to college.


----------



## Cloudy

I've been taking ~30mg of DXM HBR every other day (seeing the effects on the gastrointestinal tract in the morning), and about to start taking it everyday starting tomorrow.  I'm taking 45-90mg of adderall a day, and am hoping it'll cut down the tolerance back to 30mg a day.  I'll be taking a 2 week break from amps to also aide in the tolerance lowering.


----------



## Dunno

Has anyone using Xanax experienced a lowered tolerance when taking DXM in the form of Robitussin cough syrup?

Thanks


----------



## Dunno

Also could the combination of DXM Syrup & Mirtazapine still work at lowering tolerance as i sometimes use it for sleep. Mirtazapine is an antagonist/inverse agonist at the following receptors:

* 5-HT2A receptor 
* 5-HT2B receptor 
* 5-HT2C receptor 
* 5-HT3 receptor 
* 5-HT7 receptor


----------



## Wizzle

I'm on my first day of a dxm regimen.. took 60 mg XR.. will take 60 again later today. Might try 90 mg's tomorrow, see how that goes.

edit: The stuff makes me drowsy  I'll see if it does the same thing tomorrow.


----------



## avcpl

Wizzle said:


> I'm on my first day of a dxm regimen.. took 60 mg XR.. will take 60 again later today. Might try 90 mg's tomorrow, see how that goes.
> 
> edit: The stuff makes me drowsy  I'll see if it does the same thing tomorrow.



DXM makes me drowsy too, so this is my concern. 

I would really like to know that if taking 60mg at night for 14 days would be the same for tolerance reversal as 60mg twice a day for 7 days..


----------



## Payn

i wonder, how much DXM should i take daily to avoid building a tolerance to Phenibut? How much do i need?


----------



## Wizzle

I was wondering, some of you guys are talking about Delsym, which has 30mg DXM HBr. That's equivalent to 22,5 mg's dextromethorphan. 

The type I take called "DARO" has 40 mg's DXM HBr. That's equivalent to 30 mg's DXM.. I take 80 mg's time-released HBr DXM. (60 mg of actual DXM)

So when you guys are saying you take 60 mg's you are only taking 45 mg's? I dunno, I don't like to take it during the day because it makes me too drowsy. At night is fine though.

Getting these caps is a pain in the ass too.. I don't like to lie.

Are NMDA-receptors connected in any way to libido? I seem to be getting a big hard boner all the time  ...


----------



## chaos_destroy

^well your using it for ritalin right? I don't know about ritalin but other dopamine drugs sure can cause hyper sexuality so maybe its boosting that aspect?


----------



## Wizzle

The thing is, I am not using methylphenidate at this moment. I am abstaining from it as long as I'm taking the dxm


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## adhd1921

I took DXM nightly (about 200mg) for a year and didn't even know it was recreational. It wasn't until I told some kid that I had a huge bag of DXM powder that I ever took it recreationally.

It is most definitely incredibly useful for lowering tolerance. I went down in my dosage of Dexedrine and got back the motivational/anti-depressant effects.


----------



## Wizzle

I'm taking it twice a day again. 30 mg's during the day and 60 at night.. Works fine like this.

@adhd1921

200 mg's seems like a hefty dose, is this 200 mg's of the Hydrobromide salt? I don't think I can take such a dose without getting some weird effects.. 80 mg's makes me feel a little drowsy already.


----------



## M Brace

avcpl said:


> Mbrace, as MeDieViL stated above, that the NMDA antagonist benefit should remain, so would you really need to take the DXM so close to the MDMA?
> 
> Maybe first try the DXM 60mg 2x/day for a week for tolerance reversal/upregulation and then wait a week (or more) before you roll?



SOoooo - What is the half-life of DXM (source robitussin DXM hbr)?    I've seen conflicting info -  5 hours / 30 hours...?  Is one week after cessation of DXM long enough to wait before taking mdma?  One day?  Two days?   Sorry if this has been covered, it would be great to get some sourced information on this.


----------



## avcpl

Well on the bottle it says "wait two weeks after stopping the MAOI drug", so I would imagine you can't go wrong if you wait two weeks. 

Two weeks is what I generally use as a rule of thumb for most things; as long as you are not doing anything else that would cause downregulation or tolerance, then even longer should work too I would imagine.


----------



## MeDieViL

Been a bit busy, will answer everyone's questions soon.


----------



## Dunno

Upped Alprazolam dose on some days as i had to so cant give accurate answer but for the most part DXM in the form of Robitussin 60mg twice a day seemed to work. I will give this another go in about a week


----------



## Dunno

As a once off. would having 600mg of DXM one night reverse tolerance?


----------



## ferinox

I frequently hear about people never getting effects off of small doses of hydrocodone after developing a considerable opioid habit. My habit peaked at 100 mg oxycodone. After tapering, I'm still able to get high off of 15 mg hydrocodone. 

I take huperzine a (NMDA antagonist)400 mcg daily, dextromethorphan polistirex (NMDA antagonist) 120 mg daily, and melatonin(Nitric oxide synthase inhibitor) 3 mg daily. Probably each one of these plays some role in my high resistance to developing tolerance.


----------



## Wizzle

I took 150 mg of dxm in total yesterday, all of it near the end of the day.. 

During the day I took a total of 90 mg's mph, because I had to work.. Today is the last day that I will be off my meds. I plan to take as much dxm as possible without adverse effects. I will let you guys know tomorrow how the MPH is working.


----------



## LoveHateLove

Hey Bluelight, been lurking for a while here but I've decided it's time to contribute my experience in regards to this interesting topic.  

The only NMDA antagonist I have experience with is Memantine, which I began using to help curb my growing Adderall tolerance (RX'd 20mg XR x 2).  For this purpose I've found it to be quite effective, and at only 10mg per day.  My tolerance dropped drastically after a short break from the stimulant.  The Adderall also feels smoother and less "moreish".  The comedown is also less intense.  

Now I'm hoping it will aid me in kicking my current Valium addiction.  I recently crossed over from Klonopin (approx 1-2mg daily for a year) and I'm close to completely stablized on 15mg Diaz per day.  I've bumped up my Memantine to 15mg (7.5 AM, 7.5 PM).  I know that's a low dose but the brain fog can be pretty intense for me.  Once that clears up I'll start the taper, see how things go, and update on my progress.  Let the fun begin .


----------



## Wizzle

Good luck man.. I wish I had memantine.. Took a little too much dex yesterdaynight and it took me 3 hours to really fall asleep because I was borderline tripping. Took my mph dose just now, will let you guys know when I get back from work.


----------



## MeDieViL

Il be trying low MXE doses (5-10mg) every 3 hours soon as a replacement for memantine.


----------



## Wizzle

Why are you switching. And is there any reason beyond legality that you would choose methoxetamine over ketamine, memantine or dxm?


----------



## MeDieViL

Ive been out of memantine for a while now due to lack of funds, should get it again in the future tough, MXE seems the most interesting of the others, cant take DXM as i take AMT daily.


----------



## Wizzle

Care to elaborate? I suppose I like the idea of ketamine and analogues because they are so effective as anti-depressants.. (and thus might do a better job at receptor upregulation). These are just ideas and not facts though.


----------



## MeDieViL

Just want to try, not sure wheter it will work yet.


----------



## avcpl

MeDieViL, I'm still curious on your thoughts on DXM extended release (Delsym) or regular Hbr.  

Is there any evidence that one is better than the other for tolerance reversal? 

I was thinking the Hbr would be better since it might metabolize into DXO faster, which is apparently a much stronger antagonist. But I didn't know if there was evidence that steady plasma levels is better...


----------



## MeDieViL

avcpl said:


> MeDieViL, I'm still curious on your thoughts on DXM extended release (Delsym) or regular Hbr.
> 
> Is there any evidence that one is better than the other for tolerance reversal?
> 
> I was thinking the Hbr would be better since it might metabolize into DXO faster, which is apparently a much stronger antagonist. But I didn't know if there was evidence that steady plasma levels is better...



I'm not sure actually mate, both appear to work well.


----------



## Wizzle

It seems that my methylphenidate is getting more effective.. I'm also noticing side effects like sweating a lot.. I'm gonna try a lower dose to see if that's effective.

I'm pretty excited about the results, too bad about sides being more pronounced but that's how they were in the beginning so it was to be expected.


----------



## MeDieViL

Wizzle said:


> Right, and the striatum is hypothesized to be involved in sustained and selective attention right?



Its more complex then that, ADHD is mostly hypofunctioning of the prefrontal cortex, increased dopamine levels induced by stimulants counteract that by activating the D4 receptors, D4 doesnt downregulate however its the other receptors implicated in euphoria and the other effects of stimulants, because D4 doesnt downregulate tolerance in most cases to the anti ADHD effects doesnt occur.

However hypofunctioning of the other receptors can also cause ADHD symptons, wich is why some individuals with ADHD do build a tolerance rapidly.

To answer your original question, yup but it does a shitload more too, allmost all the damn dopamine receptors are located in the striatum.


----------



## MeDieViL

ferinox said:


> I'm pretty sure I remember reading that glutamate is heavily involved in fear extinction so maybe it's not a good treatment for anxiety. I still use opiates in combination with dxm to allow self medication with less unfortunate effects like tolerance and heavy dependence. Nothing treats my anxiety and depression so effectively. Eventually if I want my life to go anywhere, I might have to reconsider this method of treatment. If only I had adequate money, I could medicate and go to college.



Some ppl may benefit best from NMDA agonists combined with therapy yes, but as with all mental disorders i beleive they can be caused both by passed events, or learned fear and also hypofunctioning, simular to something we see in ADHD, if in your case the last thing is the case, i see nothing wrong with this treatment.


----------



## ferinox

MeDieViL said:


> Some ppl may benefit best from NMDA agonists combined with therapy yes, but as with all mental disorders i beleive they can be caused both by passed events, or learned fear and also hypofunctioning, simular to something we see in ADHD, if in your case the last thing is the case, i see nothing wrong with this treatment.



Thanks for the reply. I see nothing wrong with the treatment either except the cost. Opiates on the street are expensive except for heroin. I need to know what dose I'm taking though. I have asperger's syndrome which has a high rate of co-morbid anxiety disorders. From my memory, I've been anxious my whole life. It certainly has something to do with my neurochemical balance. 

I'm about to try kratom. It's a mu agonist and delta agonist. Delta agonists seem to have antidepressant and anxiolytic effects at least in studies. Maybe in combination with a NMDA antagonist, It could be a long term cheap solution. I really wish the medical establishment would consider opiates in refractory cases. The other antidepressants seem to have no primary effects and nasty w/d effects to add insult to injury.


----------



## crOOk

I'm only starting to realize how godamn powerful DXM can really be when it comes to tolerance. Details will follow...


----------



## MeDieViL

crOOk said:


> I'm only starting to realize how godamn powerful DXM can really be when it comes to tolerance. Details will follow...



Haha, that got me interested


----------



## MeDieViL

This may sound like a crazy idea.

But in case i would want to get some human study's started showing the effiacy of NMDA antagonists against tolerance, what would i need to do?

Looking at the potential its damn worth investing in this! Just need to find the right people haha.


----------



## Wizzle

maybe contact PsyQ in the hague.. They do a lot of work on adhd and addiction. Doing a trial with adhd-outpatients on medication effectiveness after a set amount of weeks with and without nmda-antagonists should be fairly easy and cheap to set up right?


----------



## MeDieViL

Ok, bedankt voor de tip kerel!


----------



## Wizzle

Graag gedaan! Het lijkt me geweldig als er wat van komt, hier moet echt iets mee gedaan worden!


----------



## MeDieViL

Been taking low doses of mxe every 3 hours but it seems to inhibit the dopaminergic effects of the low daily doses of AMT i take (7,5mg) now it feels like a day long dose of mdai wich makes me damn tired, been sleeping most of the time the last 2 days lol, mdai is way to sedating on its own for me too.


----------



## Dunno

Gonna try 600mg DXM in the form of robitussin later. See if Alpraz tolerance is lowered tomorrow


----------



## YaniCZka

This is really great thread! For how long does one have to take small doses of dxm to lower the tollerance?Would be lets say 3 days prior to stimulant consumption enough? Cheers.


----------



## Depressicaa

Memantine is a great tolerance reducer. 

3 days of low DXM? Why not just one day of high DXM (P3)? It worked right after in my experience. I dunno what your body weight is and what a low dose to you is either.


----------



## ferinox

Is huperzine a an adequate NMDA antagonist? I had to get codeine this week instead of hydrocodone. It appears that DXM is an inhibitor of cyp2d6. I can barely get any effects of the codeine while DXM. I don't want my tolerance to skyrocket though.

I took 360 mg codeine today using DXM and it was about the same as what I would have gotten off of 20 mg hydrocdone.


----------



## YaniCZka

Depressicaa said:


> Memantine is a great tolerance reducer.
> 
> 3 days of low DXM? Why not just one day of high DXM (P3)? It worked right after in my experience. I dunno what your body weight is and what a low dose to you is either.



thanks for reply. well tbh i read lots of bad stuff about dxm and how damaging it is for body. also seems to deplate your seretonin if used recreationally. I am around 55kg so was thinking about doing 30mg for a couple of days prior to mephedrone/mdma/speed use. or would be better to do low dose (10-20mg) of Ket instead?


----------



## Tomer

Would like to hear some opinions on this...

I have used DXM to lower my amphetamine tolerance in the past.  I have noticed there seems to be a rise in blood pressure from combining the two, which results in more taxation on my heart.

Can anyone confirm this, or is this simply my imagination?  DXM absolutely reduces my tolerance, but I'm wondering at what cost.  Should I be worried about the safety of this?  I usually only take 15mg's worth of the DXM Extended Formula in conjunction with 5-10 mg's of Dexedrine.

Tomer


----------



## deckmunki

Is DXM a dopamine reuptake inhibitor like ket is (and methoxetamine is thought to be)?

If so, surely that would explain any rise in blood pressure when combining with dopaminergic stimulants?


----------



## bben

deckmunki said:


> Is DXM a dopamine reuptake inhibitor like ket is (and methoxetamine is thought to be)?
> 
> If so, surely that would explain any rise in blood pressure when combining with dopaminergic stimulants?



Im pretty sure dxm hits opiate receptors at high doses and is an ssri as well. Dont think its a DRI like ketamine.


----------



## wreckhead

I'm using 30mg memantine + 120mg DXM per day to slow tolerance to (primarily) Dexedrine and dihydrocodeine.  Also cannabis, clonazepam and nicotine.  As I take so many drugs (despite some being prn and not daily), it'd be a fair assumption that my anti-tolerance needs are gonna be substantially greater than someone just focusing on one drug, and a tiny 10mg memantine dose, for example, just ain't gonna cut it.

Before I was just using memantine for tolerance and, although it seemed to mildly help, it wasn't enough to allow more than 1 day on / 2 days off type dosing of Dex (I have a naturally very rapid tolerance to Dexedrine in particular).  Similar for DHC (I rotate between Dex days, DHC days, and break days for anhedonia etc.).  Since I added 2 x 60mg DXM into the mix a few days ago, I noticed I was able to sustain the amphetamine mood effect for 2 days instead of 1, before requiring a break to get back to where I was prior to dosing.  It might be that now I can do 2 days on / 1 day off, the inverse of my previous usage pattern.

As my tolerances to Dex and DHC are both high due to laziness in taking breaks, I'll need a 3-5 day break to get tolerance down to near baseline.  Then I'll be able to properly test the effect on tolerance.

Some observations on tolerance preventing:


Memantine above 40mg brought with it severe cognitive impairment that didn't fade away with the adaptation time.  That's why I'm not just using a big dose of memantine rather than two NMDA modulators together, though I'll probably go back up to 40mg at some point.  50 and 60mg were the problematic doses.


As someone mentioned, the BP and heart rate increase from Dexedrine seems to have been mildly but noticeably increased since adding DXM on top of memantine.  Whether this is just a general effect of NMDA blocking, or something more specific to the pharmacodynamics of DXM, I dunno.  But I wouldn't want to take stimulants on a recreational DXM dose (not that I'd have any reason to anyway) based on experience with 120mg/day.


NMDA antagonists do indeed appear to speed up the reversal of tolerance, in addition to slowing the development of tolerance.

Oh yeah, I also use 100-150mg/day of amisulpride (presynaptic selective doses) in combination with Dexedrine, on the days I take it.  This is on my theory that as stimulants increase synaptic DA, it in turn agonises D2/D3 autoreceptors and inhibits DA synthesis + release as part of the feedback loop, accounting for the biphasic progression of stimulant effects like such - mood lift (for a number of hours) -> possible crash -> lingering stimulation with no euphoria or mood lift, fading slowly as the drug clears your body.  A study stated D2 autoreceptors inhibit DA synthesis via reduction of tyrosine hydroxylase, and D3 autoreceptors inhibit DA release.  One would assume releasing agents like amphetamine aren't vulnerable to the D3 autoreceptors (as they force dopamine release from the presynaptic neuron) but are to D2-mediated DA synthesis reduction, while reuptake inhibitors like MPH would be affected by both.

When I took Dexedrine alone before, I got around 2-3 hours of balanced mood/stimulatory effects, followed by a crash (pretty mild still - memantine at work?) for 1 hour or so, followed by neutral mood with adrenergic stimulation tapering down over 3-6 hours (approx.).  However, combined with low dose amisulpride, the initial "mood phase" didn't really shift into the crash/stimulation part nearly as much, and instead remained relatively balanced for the duration (naturally declining with time, but I got about double the time I had than before in the positive mood phase).  I'm guessing amisulpride blocked the D2 autoreceptors in particular from sending their "halt TH now!" message upon amph's increasing of synaptic DA, and as a result L-dopa->DA levels weren't shot down by the time a few hours had passed (which before gave the crash / loss of hedonic effect) and the positives were free to continue for longer.  Amisulpride had a similar effect on MPH if I recall correctly.  I do know that receptor desensitisation also plays a role in the crash etc., but I think those autoreceptors do have a big part in it all.  ...Very reductionist and pseudosciencey I know, but whatever, I did say it was only a theory & I'm no scientist.

Amisulpride has poor central vs. peripheral selectivity, which isn't usually good (man-boobs and stuff), but in combo with a stimulant this could be beneficial, as in the brain it'd be at presynaptic-selective concentrations, while peripherally it'd be also acting postsynaptically, and oppose the peripheral dopaminergic effects of stimulants including nausea/appetite suppression.  It seems to help appetite a bit for me, although amp still has a major anorexic effect overall.


----------



## MeDieViL

2 days? try to double the DXM dose, you should be able to take amphetamine even in recreational doses for weeks on end without any sign of tolerance.


----------



## MeDieViL

Ive tried memantine up to 80mg, i doubled the dose from 40mg, to prevent severe side effects i loaded up on 20 gram of piracetam wich inhibits the initial side effects quite well, i still felt pretty dizzy and had a doube vision, saw everytime the same car or person twice in front of me, wich went away after several days, worked like a charm with amphetamine but felt a bit impaired without it, felt quite confused when i took the train to work, so lowered to 60mg again wich in my case worked excellent without any noticable impairement. Tough many ppl would get quite a big of cognitive impairment above 40mg.


----------



## polymath

Another way to reverse the tolerance to opioids and other drugs is to take nitric oxide synthase inhibitors like nitroarginine, see http://www.ncbi.nlm.nih.gov/pubmed/9635893 . Actually the NMDA antagonists inhibit NOS too, but by an indirect mechanism. This probably explains their tolerance reversing effect.


----------



## Cloudy

^constriction doesn't sound to pleasant of a side effect especially if it used to try and reduce amphetamine tolerance..


----------



## SangerRainsford

ferinox said:


> I frequently hear about people never getting effects off of small doses of hydrocodone after developing a considerable opioid habit. My habit peaked at 100 mg oxycodone. After tapering, I'm still able to get high off of 15 mg hydrocodone.
> I take huperzine a (NMDA antagonist)400 mcg daily, dextromethorphan polistirex (NMDA antagonist) 120 mg daily, and melatonin(Nitric oxide synthase inhibitor) 3 mg daily. Probably each one of these plays some role in my high resistance to developing tolerance.



Re the tolerance, seems some people, once they hit a point of tolerance, they'll almost never reach a "low" level again that they can feel.  Others do.  Def be happy you're one of them, if you can get high off 10% your original dose (well, "peaked" could mean you did 100mg once, or did it daily for months - big difference here).

Re your melatonin, if you're using it as a "nitric oxide synthase inhibitor", no comments there, but if you're doing it for sleep of any sort, I'd lower it 

Re the club moss (hupzerzineA), remember also that it's a (quite potent if I'm correct, actually) acetylcholinasterase-inhibitor, and there is a significant concern for withdrawal/hangover/whatever effects to huperzineA, so yeah keep that in mind!



Dunno said:


> Upped Alprazolam dose on some days as i had to so cant give accurate answer but for the most part DXM in the form of Robitussin 60mg twice a day seemed to work. I will give this another go in about a week


interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work".  I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak 



LoveHateLove said:


> The only NMDA antagonist I have experience with is Memantine, which I began using to help curb my growing Adderall tolerance (RX'd 20mg XR x 2).  For this purpose I've found it to be quite effective, and at only 10mg per day.  My tolerance dropped drastically after a short break from the stimulant.


I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective.  Tolerance dropped after short cessation of stimulants".  Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both?  Plz clarify the roles you think both took if you can 



LoveHateLove said:


> Now I'm hoping it will aid me in kicking my current Valium addiction.  I recently crossed over from Klonopin (approx 1-2mg daily for a year) and I'm close to completely stablized on 15mg Diaz per day.


Good for you!!  Very good!!  Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile   Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).



LoveHateLove said:


> I've bumped up my Memantine to 15mg (7.5 AM, 7.5 PM).  I know that's a low dose but the brain fog can be pretty intense for me.  Once that clears up I'll start the taper, see how things go, and update on my progress.  Let the fun begin .


??
You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"??  To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been?  Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)



MeDieViL said:


> simular to something we see in ADHD, if in your case the last thing is the case, i see nothing wrong with this treatment.


It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.



MeDieViL said:


> Some ppl may benefit best from NMDA agonists combined with therapy yes,


I'd say people benefit most from therapy, and if necessary, drug intervention (which would include maintenance drugs, taper-drugs <sometimes the same chemicals fwiw>, any "anti- tolerance/dependence/craving drugs", whether naloxone or memantine, and obviously, symptom management (sleep, bowels, etc) wherever/as needed.



MeDieViL said:


> but as with all mental disorders i beleive they can be caused both by passed events, or learned fear and also hypofunctioning,


I'm a bit unclear on your meaning here - surely you're not referring to that as a basis for "all mental disorders", or are you?  Are you referring strictly to ADHD?  Just curious because I've never seen a single model of addiction that did not account for the "nature" side of things, I mean clearly people suffer addiction as both a result of the stimuli (drugs) and how they respond (nature + nurture).



MeDieViL said:


> This may sound like a crazy idea.
> 
> But in case i would want to get some human study's started showing the effiacy of NMDA antagonists against tolerance, what would i need to do?


Isn't that what this thread is?  P
Without the slightest bit of sarcasm, I'd say one of two routes:
SOLO:
- learn far more about pharmacokinetics and the brain, 
- accumulate some cash to get it going (you said you were close to broke - a basic/cheap "study" would be easy, hell one has already been done here - but you need real cash to get a study anyone's going to care about)
WITH HELP:
- could start petitions on bl/internet/MAPS (applicable?)/erowid/online-anywhere,
- apply for a "normal" grant (w/o the 1st requirement under "solo", I'd imagine you'll get nowhere here - also, weigh your prior work in the area, knowledge of the area, education/resume, and ask yourself if you see sponsorship/grant dollars flowing your way) 
<<If you don't mind me asking, are you a student, hobbyist, scientist, a combo of those?  Have you ever been involved in human trials?  How extensive is your knowledge/work in this area already?>>



MeDieViL said:


> Looking at the potential its damn worth investing in this! Just need to find the right people haha.


Something's only worth what the market will give - if someone pays, it was worth it, if not, it likely wasn't (market's aren't perfect, well except on paper  ).  Sry, the economics dork comes out lol



MeDieViL said:


> Ive tried memantine up to 80mg, i doubled the dose from 40mg, to prevent severe side effects i loaded up on 20 gram of piracetam wich inhibits the initial side effects quite well, i still felt pretty dizzy and had a doube vision, saw everytime the same car or person twice in front of me, wich went away after several days, worked like a charm with amphetamine but felt a bit impaired without it, felt quite confused when i took the train to work, so lowered to 60mg again wich in my case worked excellent without any noticable impairement. Tough many ppl would get quite a big of cognitive impairment above 40mg.


I'm confused - you're saying that it "prevented severe side effects" but went on to mention some severe sides you had.  You also say "worked like a charm".  Kinda confused here..  also, if you're really onto the memantine (or ketamine I guess, but that/DXM were never really your approaches per se, just other nmda antagonists that others tried/you supported)


----------



## SangerRainsford

WHOA!!!!!!!!!! Apologies for the length of that, haven't slept in quite a bit, and tend to drag text to doc's then cut/paste it back, makes it tougher to realize how huge it comes out 

Wish I was here when this thread began so I coulda tagged along from the get-go...

MeDieViL, don't take anything I said disparagingly - I will say some q's/points I've been making in posts today are kinda 'devil's advocate' types of replies, and I'm not really one to insult/talk down anyways, or so I like to think


----------



## Dunno

Quote:
Originally Posted by Dunno View Post
Upped Alprazolam dose on some days as i had to so cant give accurate answer but for the most part DXM in the form of Robitussin 60mg twice a day seemed to work. I will give this another go in about a week -

interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work". I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak 

Ive always been on alprazolam never took a day off - trying 120mg daily as of today again


----------



## SangerRainsford

I'm sorry I misspoke.  
Your result here, "seemed to work", is invalidated by the fact you changed your xanax dosage.  
Sorry if my meaining isn't clear, super tired now lol


----------



## MeDieViL

SangerRainsford said:


> WHOA!!!!!!!!!! Apologies for the length of that, haven't slept in quite a bit, and tend to drag text to doc's then cut/paste it back, makes it tougher to realize how huge it comes out
> 
> Wish I was here when this thread began so I coulda tagged along from the get-go...
> 
> MeDieViL, don't take anything I said disparagingly - I will say some q's/points I've been making in posts today are kinda 'devil's advocate' types of replies, and I'm not really one to insult/talk down anyways, or so I like to think



No worry's, i'l reply to everything soon, i'm a bit unsure what you mean with severe memantine side effects i have? Cant remember any of that unless you mean the initial side effects of the adaptation phase from jumping 80 at once from 40.


----------



## LoveHateLove

SangerRainsford said:


> I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective.  Tolerance dropped after short cessation of stimulants".  Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both?  Plz clarify the roles you think both took if you can
> 
> 
> Good for you!!  Very good!!  Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile   Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).
> 
> 
> ??
> You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"??  To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been?  Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)
> 
> 
> It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.


It's a combo of both, but it's better with memantine.  Now (on 15mg mem) I only take sunday's off Adderall.  In terms of tolerance reduction, that one day off is equal to probably 3-5 days sans memantine.  So I go from being able use therapeutic stim doses 3-4 days a week to 6.

As far as my benzo taper goes, I was already stabilized at 10mg memantine, this wasn't a random experimental idea thrown into the mix.  I experience brain fog _above_ 15mg.  Seeing as it's main purpose for me is amphetamine tolerance (but it _could_ possibly help with coming off benzodiazepine's) I saw no reason to remove it.

Btw I feel the main contributor to my anxiety/depression is my inattentive ADD (which went untreated until less than a year ago).


----------



## Dunno

SangerRainsford said:


> I'm sorry I misspoke.
> Your result here, "seemed to work", is invalidated by the fact you changed your xanax dosage.
> Sorry if my meaining isn't clear, super tired now lol



Yeah nothing new i always use bout 14-16mg in certain situations even when i first started bout six years ago


----------



## Dunno

Day 2 of DXM wwill try avoid situations where i need to increase my dose lol


----------



## avcpl

ok! finished we 6 days of 120mg dxm daily on friday.  we did the hbr at night and the delsym during the day. also took 200mg of chelated magnesium at night. 

tried our usual oxycodone dose yesterday (sunday) and it actually did make a difference! it was significantly stronger than the last time we used it, two weeks ago. I don't think it was a placebo effect, since I am a born skeptic; I usually introduce an anti-placebo effect if anything.

The only bad thing is that the side effects were increased too--that is the itchiness. I know we're in the minority here that lots of people like the itchiness of opiates, but it drives me crazy and too much antihistamine ruins the high.  Gonna try hydrocodone next weekend and see if that works any better. 

we roll in four weeks so we'll see how it affects our mdma tolerance.  

thanks to everyone for all the info!


----------



## MeDieViL

SangerRainsford said:


> Re the tolerance, seems some people, once they hit a point of tolerance, they'll almost never reach a "low" level again that they can feel.  Others do.  Def be happy you're one of them, if you can get high off 10% your original dose (well, "peaked" could mean you did 100mg once, or did it daily for months - big difference here).
> 
> Re your melatonin, if you're using it as a "nitric oxide synthase inhibitor", no comments there, but if you're doing it for sleep of any sort, I'd lower it
> 
> Re the club moss (hupzerzineA), remember also that it's a (quite potent if I'm correct, actually) acetylcholinasterase-inhibitor, and there is a significant concern for withdrawal/hangover/whatever effects to huperzineA, so yeah keep that in mind!
> 
> 
> interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work".  I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak
> 
> 
> I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective.  Tolerance dropped after short cessation of stimulants".  Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both?  Plz clarify the roles you think both took if you can
> 
> 
> Good for you!!  Very good!!  Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile   Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).
> 
> 
> ??
> You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"??  To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been?  Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)
> 
> 
> It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.
> *I ment that it is extremely unlikely that anxiety or other disorders cant be mediated by neurochemical issues, simular to how ADHD is caused by (mostly DAT, tyrosyne hydroxilase, D4, etc) dysfunctioning of other receptors or other issues can also manifest in things like anxiety, if thats the case then using medication is the preferred route abose therapy (assuming therapy wont work here like with adhd).*
> 
> I'd say people benefit most from therapy, and if necessary, drug intervention (which would include maintenance drugs, taper-drugs <sometimes the same chemicals fwiw>, any "anti- tolerance/dependence/craving drugs", whether naloxone or memantine, and obviously, symptom management (sleep, bowels, etc) wherever/as needed.
> 
> *What makes you say most ppl would benefit mostly from therapy? Id say it could vary dramatically, and that medication definatly shouldnt be disregarded as a long term solution.*
> 
> 
> I'm a bit unclear on your meaning here - surely you're not referring to that as a basis for "all mental disorders", or are you?  Are you referring strictly to ADHD?  Just curious because I've never seen a single model of addiction that did not account for the "nature" side of things, I mean clearly people suffer addiction as both a result of the stimuli (drugs) and how they respond (nature + nurture).
> *I ment that all mental disorders can be caused by either learned fears or passed events and also because of neurochemical issues.*
> 
> Isn't that what this thread is?  P
> Without the slightest bit of sarcasm, I'd say one of two routes:
> SOLO:
> - learn far more about pharmacokinetics and the brain,
> - accumulate some cash to get it going (you said you were close to broke - a basic/cheap "study" would be easy, hell one has already been done here - but you need real cash to get a study anyone's going to care about)
> WITH HELP:
> - could start petitions on bl/internet/MAPS (applicable?)/erowid/online-anywhere,
> - apply for a "normal" grant (w/o the 1st requirement under "solo", I'd imagine you'll get nowhere here - also, weigh your prior work in the area, knowledge of the area, education/resume, and ask yourself if you see sponsorship/grant dollars flowing your way)
> <<If you don't mind me asking, are you a student, hobbyist, scientist, a combo of those?  Have you ever been involved in human trials?  How extensive is your knowledge/work in this area already?>>
> *I'm not a student, heck i dont know wheter i can ever properly study, i never finished highschool and have a bad criminal record, not the best situation.** I just have a big intrest in all of this.*
> 
> Something's only worth what the market will give - if someone pays, it was worth it, if not, it likely wasn't (market's aren't perfect, well except on paper  ).  Sry, the economics dork comes out lol
> 
> 
> I'm confused - you're saying that it "prevented severe side effects" but went on to mention some severe sides you had.  You also say "worked like a charm".  Kinda confused here..  also, if you're really onto the memantine (or ketamine I guess, but that/DXM were never really your approaches per se, just other nmda antagonists that others tried/you supported)



Never had severe side effects with memantine, the closest to severe was the adaptation but that wasnt really bad either.


----------



## MeDieViL

avcpl said:


> ok! finished we 6 days of 120mg dxm daily on friday.  we did the hbr at night and the delsym during the day. also took 200mg of chelated magnesium at night.
> 
> tried our usual oxycodone dose yesterday (sunday) and it actually did make a difference! it was significantly stronger than the last time we used it, two weeks ago. I don't think it was a placebo effect, since I am a born skeptic; I usually introduce an anti-placebo effect if anything.
> 
> The only bad thing is that the side effects were increased too--that is the itchiness. I know we're in the minority here that lots of people like the itchiness of opiates, but it drives me crazy and too much antihistamine ruins the high.  Gonna try hydrocodone next weekend and see if that works any better.
> 
> we roll in four weeks so we'll see how it affects our mdma tolerance.
> 
> thanks to everyone for all the info!



Cool thx for your update mate.


----------



## Wizzle

Would lower dosis then 120 mg have a similar effect? I'm considering using it daily alongside mirtazapine and methylphenidate, but don't really want to take more then 50 mg a day because of possible serotonergic side effects and other possible interactions. The serotonergic action of dxm at >90 mg's sucks as is for me, I cannot stand 200 mg's of 5-htp either. I get crazy insomnia from both at those dosages. The mirtazapine will probably make it even worse so it might be a bad idea after all.


----------



## MeDieViL

Yes, 60mg 3 times a day should work too.


----------



## MeDieViL

Comeon guys, anyone else that needs to get rhid of some tolerance? Give this shit a try!


----------



## M Brace

MeDieViL said:


> Comeon guys, anyone else that needs to get rhid of some tolerance? Give this shit a try!



I'm at day 5 of a planned 7 day regimen of 120 mg per day of dxm, taken as 60mg in the morning and again in the early evening, with the hope that this will reverse some of my tolerance to mdma.

I'm also on a break from mdma.  I had planned on going several months,  and trying this a couple weeks before rolling, but I actually had a bad, bad cough and figured what-the-hell, might as well take the opportunity to drink the syrup.  

I've never used dxm recreationally before.  The first few days were not as easy as I hoped, but I think my body has gotten used to it now.  

I'm still not clear on a couple of issues concerning this dxm tolerance reversal hypothesis:

1.)  How long do I really need to wait between the end of my dxm regimen before rolling?  Someone said earlier in this thread to wait two weeks, because of the info on the standard warning label, but I think that's a misinterpretation of the data on the label, which seems to me to say _wait two weeks after stopping an MAOI before taking dxm. _ 

2.)  Is the tolerance reversal a semi-permanent neuro plasticity adaptation ?  Can I wait two weeks after stopping dxm and still expect a lowered tolerance?  Can I wait a month?  A year?  

I feel a bit like the dumb kid in algebra -- which I was !?!? -- who just doesn't quite get it yet.  So thanks for bearing with me, that a-ha moment is hopefully near. 

And OMG this stuff definitely potentiates caffeine....


----------



## avcpl

Mbrace, it was I that said that about the two weeks. I realize it was about the MAOI on the label; I wasn't misinterpreting the label, I meant that would probably be a good rule of thumb, just thinking "hey, if a two week buffer is ok for maoi/dxm usage, then probably can't go too wrong with a two week buffer for dxm/mdma". Just my personal opinion, so take it for what it's worth!  
]
I believe from reading the comments in this thread that the tolerance reversal should last until you blow it again. MeDieViL has said that the NMDA antagonist benefit should remain; I don't think you would lose it by just waiting..

Me and my wife have been very impressed with how it has worked with opiates and we roll in 11 days and are really looking forward to it!


----------



## SangerRainsford

As far as I know, these NMDA changes are permanent, they don't go away (remember, this is, in essence, a "helper" in trying to reverse a drug user's brain back to baseline/normal.  You put your brain in a spot that it can benefit here, and it will benefit.  If you stop using an NMDA antagonist, or you start using again, sure you can rewire things back to an addicted/tolerant/etc state, but when you cessate usage, or speed up cessation with NMDA antagonists (or use them during usage, to slow tolerance buildup, if that is demonstratable outside of theory/anecdote), you're using a chemical to 'fix' things, bring them closer to where your body wanted it to be, so no it doesn't stop once the NMDA antonist is stopped ;-P )


----------



## Jackinbox

I just registered to the forum because I jumped on the memantine bandwagon to counteract amphetamine tolerance. I want to start Adderall again for my ADD. I take Lyrica (150mg 2x day) and started pristiq 20 days ago. Lyrica is amazing to counteract the side effects of Adderall and for anxiety. I eliminated clonazepam from my regimen thanks to Lyrica (still pop one once in while, mainly to sleep). 

Pristiq is a pain since it make me feel tired but "nervous" at the same time (can't stop shaking my legs). I don't think I will keep it for long but I give it a try for a few more weeks.

Without Lyrica I could barely handle 10 mg of Adderall. I can go up to 30 mg with my current dose of Lyrica. (But 20 mg seems enough). Sadly, it doesn't help with tolerance.

I started memantine 2 days ago. I want to titrate fast. No brain fog noted so far at 10 mg. Others have reported that memantine greatly potentiate Lyrica. From my experience so far this seems to be true. When I took 75 mg of Lyrica Yesterday and this morning, I got a feeling of heaviness that I don't get at 150 mg. 

Too soon to report on Adderall tolerance with memantine (just popped 20 mg of Adderall and I feel great!). Usually I get about two hours of motivation and mood lifting, followed by 6-8 hours of "awakening" effect on the first day after a few days break. It take only a few days for the tolerance to develop.

Should I expect memantine to have an effect on tolerance right away or do I need to take it many days in a row before getting any benefits? 

By the way, do you guys note a difference between Adderall and Dexedrine Extended-Release?


----------



## SangerRainsford

difference between ER dexedrine and (what kind of)adderrall?


----------



## Jackinbox

SangerRainsford said:


> difference between ER dexedrine and (what kind of)adderrall?



Adderall XR


----------



## SangerRainsford

not too much, imo.  To me, the difference is, at a stretch, the difference between a few vico's and a few perc's (which had equivalent narcotic-effects, like dose-controlled)


----------



## MeDieViL

Currently im taking 60mg DXM 3 times a day combined with 666mg acamprosate 3 times a day, well see how it goes.

Goal is to prevent tolerance to dexedrine, valium and GBL.


----------



## SangerRainsford

Given this isn't too busy a thread, lemme ask you something.

I know you've been reading up on NMDA/pathways, and am curious what you've found with regards to "time til normal" after cessation of a strong NMDA agonist (coke, heroin, whatever).  How long til "rewired-to-normal"?  High/low correlation with time/dosage/administration-route? Highly individual/variable?  Just interested, I know there's no real "concrete" answers for a lot of that just yet.


----------



## MeDieViL

Can you clarify a bit more what you mean exactly?


----------



## SangerRainsford

Well, I was really hoping to just hear your thoughts.  I've been learning about NMDA, glutamate, reward pathways, neuroplasticity, etc, but it's from a non-biological-sciences-background.  I wanted to hear what you've found in the areas I'd mentioned.
If you want me to be more specific, I'd be interested to know if/what data/thoughts exist with regards to someone "returning to normal", as far as their 'circuitry' is concerned, after, say, 5yrs of crack, or 20 of xanax.  Between friends I have/am trying to help, and family who have been on addictive, doctor-sanctioned meds for decades, I have a keen interest in "recovery" and the re-wiring of these pathways.


----------



## SangerRainsford

(and further - I'm correct in that the NMDA pathway is the primary source of addiction, right?  Regardless of whether it's crack, xanax or heroin, it's dopamine/glutamate/NMDA-agonism that cause addiction (not dependence, *addiction*)


----------



## MeDieViL

SangerRainsford said:


> Well, I was really hoping to just hear your thoughts.  I've been learning about NMDA, glutamate, reward pathways, neuroplasticity, etc, but it's from a non-biological-sciences-background.  I wanted to hear what you've found in the areas I'd mentioned.
> If you want me to be more specific, I'd be interested to know if/what data/thoughts exist with regards to someone "returning to normal", as far as their 'circuitry' is concerned, after, say, 5yrs of crack, or 20 of xanax.  Between friends I have/am trying to help, and family who have been on addictive, doctor-sanctioned meds for decades, I have a keen interest in "recovery" and the re-wiring of these pathways.



Can you specify what symptons those ppl are suffering from, and what should be normalised?
I assume were talking about things like anhedonia here?

I beleive NMDA antagonists should help, but i'm a bit insure about this subject.


----------



## MeDieViL

SangerRainsford said:


> (and further - I'm correct in that the NMDA pathway is the primary source of addiction, right?  Regardless of whether it's crack, xanax or heroin, it's dopamine/glutamate/NMDA-agonism that cause addiction (not dependence, *addiction*)



NMDA, CREB, KAPPA, Mu opioid, CB1, 5HT3, GABAB and tons more receptors involved, its not that NMDA is the premirary mediated, but the nmda complex does play a keyrole in many addictions, and disrubting it with NMDA antagonism can be highly beneficial.


----------



## SangerRainsford

Okay, definitely have to scale back on the smart-talk ;P
I'm unsure what role mu-opioid receptors play in cocaine *addiction*.
To be more to the point, I was under the impression that ALL drug addiction involved the effects of dopamine in the "NMDA system".  Surely there are more systems involved in specific-drug cases, that's not what I'm referring to.  I'm referring to the common pathways shared by *all* drugs of addiction that cause the reinforcing, rewarding feelings that make one continue to use despite it being to their detriment.  Doesn't every drug-addiction involve the reward pathways, and isn't this the central role of NMDA in addiction?

I'm not talking about drug-specific withdrawals, drug-specific dependence, or drug-specific anything.  I'm talking about the long-term changes one's brain undergoes during drug addictive behavior being rewarded over and over, whether crack, heroin, even compulsive gambling - are they not all dopamine/NMDA based?  If they are, then the question is simply "how long after one stops gambling/doing crack will these changes reverse?"


----------



## SangerRainsford

Reading how you phrased your post, I just want to be clear that the distinctions between abuse, dependence, addiction, tolerance, etc in any post I made in this thread were meant in the most literal sense.  
/you think I'm referring to "tolerance" reversal, don't you?  I'm talking about addiction-reversal, reversing the changes that occured in one's brain due to years of reinforcing a "gambling feels good" sensation.  Once one stops gambling, off the bat, gambling still feels right.  At some point it doesn't feel as right.  It's my understanding this is due to the aforementioned pathways, the reinforcements that "gambling's right" for many years - once the reinforcements from drugs/gambling stop, how long til said pathways are not thinking about drugs/gambling?  I'm under the impression that the brain eventually abandons such pathways once reinforcements stop, and that it is mediated by dopamine/NMDA agonism.


----------



## MeDieViL

Hmm i understand what you mean but i have no idea how you could reverse addiction, wich is mostly programmed in the brain because of sensitization, i think the only real option is using NMDA antagonists BEFORE someone starts using drugs, in my experience NMDA antagonists have no effect on my mental addictions.

From my research i think alpha3beta4 could be the most interesting target for this (the receptor ibogaine acts in, including DXM and wellbutrin).


----------



## SangerRainsford

will look into that, thnx
and I'll try to grab something that's phrasing it better than I can.  Once one stops the behaviors, the reinforcements stop, and the brain *eventually* loses its irrational need for (gambling, drugs, etc), maybe not "loses" as much as "forgets a lot", and that this change is a result of going from normal, to reinforcing the wrong thing, then back to normal.


----------



## avcpl

had our first roll after our dxm trials.  it was our best ever and I'm sure some of that was due to doing this!   

We're wondering how often it should be done?  between every roll?  after every two rolls? 

we usually have a two and a half to three month break in between rolls...


----------



## MeDieViL

avcpl said:


> had our first roll after our dxm trials.  it was our best ever and I'm sure some of that was due to doing this!
> 
> We're wondering how often it should be done?  between every roll?  after every two rolls?
> 
> we usually have a two and a half to three month break in between rolls...



I think its time to start writing guides about this regime with experiences in all relevant forums such as the mdma forum, to get this thing really going.


----------



## thikal

This is my first post so hello to everybody, i'm one of us now! :D Really impressive thread. Thanks Medievil and other to share such great infos. I don't understand why effect on tolerance by NMDA antagonists are so less known. I have few addicts in my neighbourhood, and they don't know at all that just DXM can be a fucking help for their w/d (i was happy to tell them the "NDMA story"^^).

I'm interested to kown if some one here tried DXM and tramadol combo for reducing/prevent tramadol tolerance (just 30mg DXM)? This combo without doubt is harmfull at hight doses (serotonin syndrome and so), but can a low dose of DXM like 30mg can prevent tolerance forming?

I'm starting a 2x30mg/day DXM dosing to decrease my tolerance to both codeine, and tramadol, (and perhaps GBL, didn't take this any more, and hope it might increase methylone). I wish i'd known this when i was a GBL "heavy" user. I confess i'm totally exited and don't understand why these infos aren't spread at all in French forum. I apology for English errors, and will come back with news. Hope i will feel my next methylone intake like the first fucking soooo good one. 8)


----------



## MeDieViL

thikal said:


> I don't understand why effect on tolerance by NMDA antagonists are so less known.



I'm working hard to make it more well known, before my thread ppl barely knew about it at all or dismissed, so now i'm looking for help, ppl that can make easy to understand guide's in all subfora so more ppl can try and so hopefully make the use of NMDA antagonists for tolerance more well known.


----------



## bben

MeDieViL said:


> I'm working hard to make it more well known, before my thread ppl barely knew about it at all or dismissed, so now i'm looking for help, ppl that can make easy to understand guide's in all subfora so more ppl can try and so hopefully make the use of NMDA antagonists for tolerance more well known.



IMO nmda antagonists are not effective in everyone so they are not more widely used. The medical community is def aware though.


----------



## SangerRainsford

The med community is aware, but this kind of 'therapy' is nowhere near level IV trials yet..this is still forum-lab fodder imo


----------



## MeDieViL

bben said:


> *IMO nmda antagonists are not effective in everyone* so they are not more widely used. The medical community is def aware though.



They work for nearly everyone, i assume you have anecdotal reports confirming what you are saying? Ive repeadly asked to post too even if it doesnt work, so havent seen amny myself, perhaps you have.


----------



## Requiel

Hey MeDieViL,

Really great topic! I'd like to try memantine for tolerance prevention with dexedrine (for my ADD). But I don't know if my psychiatrist will prescribe it to me. What evidences did you show your doctor to get prescribed memantine? Or did you aquire it in some other way?

I'm from the Netherlands by the way! 

Thanks.

EDIT: By the way this is my first post here, your topic made me sign up. Too bad I can't PM yet.


----------



## thikal

Medievil have got a question to you. Do piracetam block DXM NMDA antagonism like ketamine?


----------



## MeDieViL

thikal said:


> Medievil have got a question to you. Do piracetam block DXM NMDA antagonism like ketamine?



Yes, altough piracetam and memantine are reported to synergize but its unclear how this effects tolerance issues.


----------



## MeDieViL

Requiel said:


> Hey MeDieViL,
> 
> Really great topic! I'd like to try memantine for tolerance prevention with dexedrine (for my ADD). But I don't know if my psychiatrist will prescribe it to me. What evidences did you show your doctor to get prescribed memantine? Or did you aquire it in some other way?
> 
> I'm from the Netherlands by the way!
> 
> Thanks.
> 
> EDIT: By the way this is my first post here, your topic made me sign up. Too bad I can't PM yet.



I order it online from india as the prescription is way to expensive (nearly 100 euro's).


----------



## Requiel

MeDieViL said:


> I order it online from india as the prescription is way to expensive (nearly 100 euro's).



Thanks for the reply. I'm considering buying online too, although many people advise against it. What do you think about this? And could you PM me the website you ordered from?


----------



## MeDieViL

Im having some major tolerance issues after i ran out of memantine months ago, GBL, AMT, stims, mdma, methylone all barely do anything.

I'm currently on a regime of 600mg nac, low ket bumps during the day and DXM for trying to get my tolerance to where it used to be.

Imagine 2 grams of mdma doing shit.


----------



## MeDieViL

Why DXM is more effective then memantine for tolerance:


> Methods Find Exp Clin Pharmacol. 2004 Oct;26(8):623-6.
> Protective effect of bupropion on morphine tolerance and dependence in mice.
> Joshi D, Singh A, Naidu PS, Kulkarni SK.
> 
> Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
> Abstract
> Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Bupropion (2 and 5 mg/kg) per se, when chronically administered for 9 days, failed to produce any significant change in tail-flick latency compared with the control mice. Chronic administration of bupropion (2 or 5 mg/kg) during the induction phase (days 1-9) delayed the development of tolerance to the antinociceptive action of morphine and also reversed naloxone- (2 mg/kg) precipitated withdrawal jumps. On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.





> J Pharm Pharmacol. 2009 Apr;61(4):493-502.
> Effects of co-administration of bupropion and nicotine or D-amphetamine on the elevated plus maze test in mice.
> Biala G, Kruk M.
> 
> Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland. grazyna.biala@am.lublin.pl
> Abstract
> OBJECTIVES: A variety of abused drugs, including psychostimulants, can modulate the expression of anxiety. Although the effect of nicotine and D-amphetamine on anxiety-related behaviour in animal models has been investigated, the mechanisms underlying the anxiogenic or anxiolytic actions of these drugs have not been clarified. Bupropion is an antidepressant drug which may alleviate some symptoms of nicotine withdrawal, although its effects on anxiety are not clear. We have investigated the effect of nicotine and D-amphetamine on anxiety in the elevated plus maze test in mice.
> 
> METHODS: We examined the influence of acute administration of nicotine (0.1 mg/kg, s.c.) and D-amphetamine (2 mg/kg, i.p.) on anxiety level. We then evaluated the anxiety-related response after subchronic injection of both psychostimulants, including crossover effects. For this purpose, nicotine (0.1 mg/kg, s.c.) was administered daily for six days, and on the seventh day mice were challenged with nicotine (0.1 mg/kg, s.c.) or D-amphetamine (2 mg/kg, i.p.). A distinct group of mice was pretreated with D-amphetamine (2 mg/kg, i.p., 8 days), and subjected to D-amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.) challenge on the ninth day. Moreover, we investigated acute and subchronic effects of coadministration of bupropion (5, 10 and 20 mg/kg; i.p.) and nicotine or D-amphetamine.
> 
> KEY FINDINGS: We observed that acute anxiogenic effects of nicotine and D-amphetamine as well as the development of tolerance and cross-tolerance to their effects were blunted by a pretreatment with a nonactive dose of bupropion (5 mg/kg, i.p.).
> 
> CONCLUSIONS: These results demonstrated that similar neural mechanisms were involved in the regulation of nicotine and D-amphetamine anxiety-like behaviour in mice. The results have provided new findings to support the use of bupropion in the treatment of nicotine and/or amphetamine addiction.





> Reversal of Triazolam Tolerance and Withdrawal-Induced Hyperlocomotor Activity and Anxiety by Bupropion in Mice
> Dipesh Joshi, Pattipati S. Naidu, Amanpreet Singh, Shrinivas K. Kulkarni
> 
> Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
> Address of Corresponding Author
> 
> Pharmacology 2005;75:93-97 (DOI: 10.1159/000087189)
> 
> Key Words
> 
> Triazolam
> Bupropion tolerance
> Triazolam tolerance
> Drug dependence
> Triazolam withdrawal
> Bupropion, anxiety
> Abstract
> 
> Chronic administration of triazolam (0.25 mg/kg/day, i.p.) on days 1–8 and its withdrawal produced an anxiogenic reaction in mice as assessed in the mirrored-chamber test. Daily administration of bupropion (2 or 5 mg/kg, i.p.) prior to triazolam for 8 days prevented withdrawal-induced anxiety in mice. Triazolam withdrawal also induced a significant increase in the locomotor activity of mice indicating an anxiogenic response. Daily administration of bupropion (2 or 5 mg/kg) prior to triazolam for 8 days also prevented withdrawal-induced increased locomotor activity. In conclusion, chronic administration of bupropion (2 and 5 mg/kg) exhibited a significant protection against triazolam withdrawal-induced anxiety and hyperlocomotor activity in mice. The result suggests the protective effect of bupropion in the management of triazolam withdrawal reactions.


Alpha3beta4 antagonism has besides anti craving ant tolerance effects, thus i woll add in wellbutrin to my anti tolerance stack.


----------



## chaos_destroy

MeDieViL said:


> Im having some major tolerance issues after i ran out of memantine months ago, GBL, AMT, stims, mdma, methylone all barely do anything.
> 
> I'm currently on a regime of 600mg nac, low ket bumps during the day and DXM for trying to get my tolerance to where it used to be.
> 
> Imagine 2 grams of mdma doing shit.



Thats not to encouaging. Did the tolerance just come back once you stopped the memantine or did you actually just develop it again by excessive use of said compounds? Is it worse now that prior to memantine/dxm treatments?


----------



## MeDieViL

chaos_destroy said:


> Thats not to encouaging. Did the tolerance just come back once you stopped the memantine or did you actually just develop it again by excessive use of said compounds? Is it worse now that prior to memantine/dxm treatments?



Just same build up as before nmda antagonist treatment.

After i stopped memantine i got addicted to amphetamine for a month.


----------



## MeDieViL

I think DXM doesnt work good for GBL tolerance, it also doesnt make a beer really euphoric like memantine did, ive read rodent study's how some nmda antagonists work against social defeat induced tolerance while others didnt but both worked against normal tolerance, i think there's a difference in NMDA antagonists and its possible that only memantine works against GBL tolerance.

DXM definatly works for stims and benzo's.


----------



## MeDieViL

I think DXM is just useless for tolerance in general in my case, memantine worked wondors tough, i gues its also peple dependent.


----------



## Dunno

Has anyone tried it with alprazolam & DXM Robitussin not the delsym formula for ten days instead of a week?


----------



## Dunno

Is DXM good for withdrawals ...over xanax bullshit side effects


----------



## negrogesic

DXM is.....well.....DXM.....i'll leave it at that


----------



## Dunno

ok just drink it all


----------



## M Brace

My DXM experiment was *not successful* in reducing my mdma tolerance.  In fact, it may have had the opposite effect.

About 5 weeks ago, I did 7 days of 60 mg DXM HBr-- twice per day.  

Used mdma one night, this last weekend.  Hadn't used in nearly 3 months. Before that, rolled twice in three month span.  This experience was in the bottom 3 of all time for me.  Oddly, it seems that crappy rolls happen with longer breaks for me. 

I started with 145 mg, two hours later barely felt it.  Then took another 100 mg.  Then at +2.5, insufflated approx 50 mg, took another 50 mg orally.  Started to feel the foggy comeup, which lasted about an hour.  Smoked one hit of sativa, downed a redbull.  Felt little *tiny* bits of euphoria here and there.  Ate more pills over the next 4 hours.  I don't know how many.  So much so that I had a tweaky leg for the next 24 hours... Chasing a high that I don't think I'll ever be able to catch again.  

Before and after the DXM treatment, I did lightly use alcohol and moderately used marijuana.  Also, took some benzos for sleep two or three times.  

Material was personally tested marquis/mecke/simmons, and worked great for other people. 

Perhaps the DXM benefit is not long-lasting?  I did notice that pot, especially indica strains, seemed a lot stronger in the three weeks after DXM. And I definitely felt some effect of DXM during and for the few days after taking it.   Once I pushed through the sluggishness, I felt a boost in self confidence and  the whole world looked and sounded brighter.  I really thought this was going to work.  Very bummed. Definitely hung over, and feeling stupid.


----------



## Transform

What has your MDMA use been like in the past?


----------



## M Brace

Transform said:


> What has your MDMA use been like in the past?




It's difficult to be objective - but, I'll try... Used for a few years.  Initial honeymoon period ~ once every three weeks.  Several +2 month breaks and one 3 month break. Generally about once a month.  Oddly, used way too much on occasions where it didn't "work", I'm talking close to a gram.    Usually, when I was a good boy, I took between 275mg - 500 mg per night.   Haven't had a truly "Magical" experience with mdma since those first 6 months.  Man, they were amazing!  Have had some cool combos over last two years (2CB, Psilo, K).  

Have found that a higher dose up front (200+mg), followed by small boosts (1 or 2) is much better than building up slowly.  But, when trying these various regimens (SJW, DXM, 5-HTP, L-Tyrosine, Piracetam) I'm very nervous about taking too much up front -- I did 200mg once with Piracetam and got floored and panicked on the come up.  In this last case, after the DXM deal, having read that people had experienced a dramatic reduction in tolerance, I started with too low a dose.          

Such a frustrating little puzzle, this tolerance is.  Feel really amazing emotionally yesterday and today.  The love is there, the connectedness... those components I consider magical,  they're delayed and uncoupled from the stimulant components.


I would say that my material was weak (again, it was tested personally with the big three)  but the hangover I got was so severe... 

Is there a model for DXM tolerance reduction/reversal/whatever  that would account for a temporary tolerance reduction that "wears off" after a month?


----------



## MeDieViL

M Brace said:


> My DXM experiment was *not successful* in reducing my mdma tolerance.  In fact, it may have had the opposite effect.
> 
> About 5 weeks ago, I did 7 days of 60 mg DXM HBr-- twice per day.
> 
> Used mdma one night, this last weekend.  Hadn't used in nearly 3 months. Before that, rolled twice in three month span.  This experience was in the bottom 3 of all time for me.  Oddly, it seems that crappy rolls happen with longer breaks for me.
> 
> I started with 145 mg, two hours later barely felt it.  Then took another 100 mg.  Then at +2.5, insufflated approx 50 mg, took another 50 mg orally.  Started to feel the foggy comeup, which lasted about an hour.  Smoked one hit of sativa, downed a redbull.  Felt little *tiny* bits of euphoria here and there.  Ate more pills over the next 4 hours.  I don't know how many.  So much so that I had a tweaky leg for the next 24 hours... Chasing a high that I don't think I'll ever be able to catch again.
> 
> Before and after the DXM treatment, I did lightly use alcohol and moderately used marijuana.  Also, took some benzos for sleep two or three times.
> 
> Material was personally tested marquis/mecke/simmons, and worked great for other people.
> 
> Perhaps the DXM benefit is not long-lasting?  I did notice that pot, especially indica strains, seemed a lot stronger in the three weeks after DXM. And I definitely felt some effect of DXM during and for the few days after taking it.   Once I pushed through the sluggishness, I felt a boost in self confidence and  the whole world looked and sounded brighter.  I really thought this was going to work.  Very bummed. Definitely hung over, and feeling stupid.



Much thx to report your negative experience, we also need negative reports to get a good objective view of the potential, it is possible you are one of the ppl that cant metabolise DXM correctly (it was somewhere posted in this thread) and therefor DXM wont work, or like in my case i didnt find DXM very effective for drug tolerance, altough i didnt try it long enough for stimulants, that was more my impression, i know it sucked for G tolerance tough while i had EXCELLENT results with memantine, i also remember magicalcat reporting that tolerance reversal went SLOWER when he added memantine to DXM, so it seem that ppl can respond differendly to nmda antagonists.


----------



## MeDieViL

Dunno said:


> Is DXM good for withdrawals ...over xanax bullshit side effects



Yes for those that tried it so far it lowered tolerance and helped withdrawals.


----------



## M Brace

MeDieViL said:


> ...while i had EXCELLENT results with memantine...



Did you have good results with memantine and stims ? MDMA? G?


Thx


----------



## MeDieViL

M Brace said:


> Did you have good results with memantine and stims ? MDMA? G?
> 
> 
> Thx



MDMA didnt do enough tests to give a good answer and didnt take it enough, stims without a doubt, GBL without a doubt too, i took 100ml a week for several periods.


----------



## MeDieViL

DJ Revisionist said:


> I'm going to be starting a six day 120mg Delsym regiment this weekend. Will post results in a couple of weeks.



Keep us updated mate


----------



## MeDieViL

Behav Pharmacol. 2010 Feb;21(1):1-10.
Subchronic phencyclidine in rats: alterations in locomotor activity, maze performance, and GABA(A) receptor binding.
Beninger RJ, Beuk J, Banasikowski TJ, van Adel M, Boivin GA, Reynolds JN.

Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. beninger@queensu.ca
Abstract
Phencyclidine (PCP), an antagonist at the N-methyl-D-aspartate subtype of ionotropic glutamatergic receptors, decreases gamma-aminobutyric acid (GABA)ergic inhibition, suggesting that changes in GABAergic receptor function underlie behavioral and cognitive deficits resulting from repeated administration of PCP. To test this hypothesis, male Sprague-Dawley rats treated with PCP (4.5 mg/kg, intraperitoneal, twice a day for 7 consecutive days) or saline were tested in behavioral and cognitive tasks 7 days after injections. The PCP group showed increased amphetamine (1.5 mg/kg)-stimulated locomotor activity, and exhibited a greater number of errors in the double Y-maze memory task, when compared with controls. Subchronic PCP treatment increased [H]muscimol-binding sites and decreased affinity for [H]muscimol binding in frontal cortex, hippocampus, and striatum in comparison with controls. There were no changes in the expression of glutamic acid decarboxylase or the GABA membrane transporter protein. These data show that subchronic PCP administration induces an impaired performance of a previously learned task and an enhanced response to amphetamine in the rat. The observed changes in GABAA receptors in the rat brain are consistent with the notion that alterations in GABAergic receptor function contribute to the behavioral and cognitive impairments associated with repeated exposure to PCP.


----------



## Dunno

MeDieViL said:


> Behav Pharmacol. 2010 Feb;21(1):1-10.
> Subchronic phencyclidine in rats: alterations in locomotor activity, maze performance, and GABA(A) receptor binding.
> Beninger RJ, Beuk J, Banasikowski TJ, van Adel M, Boivin GA, Reynolds JN.
> 
> Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. beninger@queensu.ca
> Abstract
> Phencyclidine (PCP), an antagonist at the N-methyl-D-aspartate subtype of ionotropic glutamatergic receptors, decreases gamma-aminobutyric acid (GABA)ergic inhibition, suggesting that changes in GABAergic receptor function underlie behavioral and cognitive deficits resulting from repeated administration of PCP. To test this hypothesis, male Sprague-Dawley rats treated with PCP (4.5 mg/kg, intraperitoneal, twice a day for 7 consecutive days) or saline were tested in behavioral and cognitive tasks 7 days after injections. The PCP group showed increased amphetamine (1.5 mg/kg)-stimulated locomotor activity, and exhibited a greater number of errors in the double Y-maze memory task, when compared with controls. Subchronic PCP treatment increased [H]muscimol-binding sites and decreased affinity for [H]muscimol binding in frontal cortex, hippocampus, and striatum in comparison with controls. There were no changes in the expression of glutamic acid decarboxylase or the GABA membrane transporter protein. These data show that subchronic PCP administration induces an impaired performance of a previously learned task and an enhanced response to amphetamine in the rat. The observed changes in GABAA receptors in the rat brain are consistent with the notion that alterations in GABAergic receptor function contribute to the behavioral and cognitive impairments associated with repeated exposure to PCP.



tRANSLATION?


----------



## thikal

So my little trials:

DXM 30mg/morning, 60mg at night during 7 days.

Useless for GBL, I had a methylone experience and noticed no difference but I suspected the seller to give me weak mephedrone instead of methylone. 

Useful for codeine tolerance, not in a fantastic way but it's a good help. I definitely add DXM to my tool box but just for a great potentiator for opiates because i'm an asthmatic and i had more difficulty breathing during my trial.


I'm gonna try to find some memantine, (and yeahh it's not a cold medicine!). Is there any danger with memantine use for an healthy man? For me, I lost "GBL magic" like you can loose MDMA magic (it's not the same at all but do you understand what i mean? You can take fucking breaks and tolerance don't move at all). I really hope that memantine will bring back the initial GBL euphoria that miss me sooo much. I love GBL and want a second chance to use it occasionally.


----------



## MeDieViL

I also found DXM useless for GBL, but it does seem to work for stimulants, i retract what i said before, something else in my medication regime was inhibiting amphetamine.

Memantine on the other hand worked excellent for GBL tolerance, it also enhances the euphoria of ethanol, something everyone notices on memantine acutely and wich has never been reported with DXM.

Memantine is a well tolerated safe med, there are a few case reports of a slower heartrate tough with one person that died, however that is extremely rare, if you are worried get a heartrate monitor.


----------



## MeDieViL

thikal said:


> So my little trials:
> 
> DXM 30mg/morning, 60mg at night during 7 days.
> 
> Useless for GBL, I had a methylone experience and noticed no difference but I suspected the seller to give me weak mephedrone instead of methylone.
> 
> Usefull for codeine tolerance, not in a fantastic way but it's a good help. I definitely add DXM to my tool box but just for a great potentiator for opiates because i'm an asmatic and i had more difficulty breathing during my trial.
> 
> 
> I'm gonna try to find some memantine, (and yeahh it's not a cold medicine!). Is there any danger with memantine use for an healthy man? For me, I lost "GBL magic" like you can loose MDMA magic (it's not the same at all but do you understand what i mean? You can take fucking breaks and tolerance don't move at all). I really hope that memantine will bring back the initial GBL euphoria that miss me sooo much. I love GBL and want a second chance to use it occasionaly.



Mate before memantine prevented loss of magic, but i ran out and lost it so i'm on the same quest to bring it back, i take around 100ml GBL a week (not physically addicted tough) lets hope for succes.


----------



## MeDieViL

Dunno said:


> tRANSLATION?



Couple of damn rats getting high on pcp and the noticing that their amphetamine is working better because their PCP abuse.

Its also interesting they note downregulation of GABAA in some area's and upregulation in other area's.


----------



## thikal

GBL took a while to have no euphoria (More than one year of sporadic use), i'm really interested to see if it will be the same after a mementine regimen. Is there any other potentials NMDA antagonists? I use to take magnesium, it helped a little bit when i suffered of anedonia thanks to GBL.

I mixed 60mg of DXM and tramadol (progressively 500mg in total) and i'm still alive but I don't recomend it to anyone... My body temperature was warm compare to tramadol alone (when i'm colder than normal, serotonine syndrome or placebo serotonine syndrome? I drank a few ricards too) I can't say if thit mix add some more, and won't do it again.

You said that mix piracetam and mementine synergise well don't you medieval (sorry for all the questions^^)? (i stoped my piracetam+choline mix for my first trial) Have a good night bluelighters!


----------



## Dunno

can say it does work....used dxm for 11 days today only needed 4mg in a social settin than usual 6mg dose. no dxm left so will see how it affects me tomorrow


----------



## Dunno

No good...will have to get back on the DXM but surprised it actually works while still taking the drug! Thanks to the OP!


----------



## MeDieViL

Good to hear mate.


----------



## itspokey

MeDieViL,

On Memantine to address GBL tolerance. 

Ive read the forum so far, but just wanted to clarify your opinion as to the best process...

On an individual who is already very GBL tolerant which has occured over a period of many years.
What would be the best reversal steps for using Memantine based on your experiences?

How fast would you expect results?

Would GBL consumption have to stop during the initial phase of taking it Memantine?
If so, for how long?

How long did you take Memantine before stopping?

When you talked about tolerance reappearing again, after memantine was stopped, could you guess how many mls of GBL it took to reappear?


Thanks!


----------



## MeDieViL

I take 100ml of GBL a week, after memantine this turned into 250ml GBL + 300ml GHB a week (i buyed from my dealer if i ordered to late). Due to my strict timing regime i never encountered any physical dependency issues tough.

Memantine acutely potentiates alcohol euphoria alot, many ppl noticed this, i have no idea wheter you need to take a break or not, initiate memantine, go to around 30 mg if that doesnt work 40mg and initially keep taking GBL if tolerance does not change then stop it and take a break.


----------



## MeDieViL

thikal said:


> GBL took a while to have no euphoria (More than one year of sporadic use), i'm really interested to see if it will be the same after a mementine regimen. Is there any other potentials NMDA antagonists? I use to take magnesium, it helped a little bit when i suffered of anedonia thanks to GBL.
> 
> I mixed 60mg of DXM and tramadol (progressively 500mg in total) and i'm still alive but I don't recomend it to anyone... My body temperature was warm compare to tramadol alone (when i'm colder than normal, serotonine syndrome or placebo serotonine syndrome? I drank a few ricards too) I can't say if thit mix add some more, and won't do it again.
> 
> You said that mix piracetam and mementine synergise well don't you medieval (sorry for all the questions^^)? (i stoped my piracetam+choline mix for my first trial) Have a good night bluelighters!



They do synergize but regards to tolerance i have no idea, its possible piracetam abolishes the positive effects on tolerance.


----------



## MeDieViL

Dunno said:


> tRANSLATION?



Basicly how a certain NMDA antagonist affects the binding of a gaba agonist to the receptors, more receptors usually means less tolerance but it depends on the brain area.


----------



## MeDieViL

> Brain Res. 2002 Nov 8;954(2):151-9.
> Valproate prevents the induction and the expression of MK-801 sensitization.
> Yang PB, Swann AC, Dafny N.
> 
> Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, PO Box 20708, Houston, TX 77225, USA.
> Abstract
> Repeated administration of psychostimulants such as amphetamine, cocaine, and methylphenidate has been shown to induce behavioral sensitization. Sodium valproate, an anticonvulsant agent that enhances GABA activity, and dizocilpine (MK-801), a non-competitive NMDA receptor antagonist, can block the sensitization elicited by psychostimulants. MK-801 also has been demonstrated to sensitize to itself. The objective of the present study was to determine whether valproate disrupts the behavioral sensitization elicited by MK-801. Male Sprague-Dawley rats were given a regimen of repeated MK-801 injections (0.3 mg/kg, i.p.) that produced behavioral sensitization. They were also given valproate, at a dosage (50 mg/kg, i.p.) that prevented behavioral sensitization to stimulants, either during or after multiple MK-801 injections. After the washout period, animals were then re-challenged with MK-801 to determine whether valproate disrupted the behavioral sensitization elicited by MK-801. An activity monitoring system recorded horizontal activity, total distance, and vertical activity of the animals following drug treatment. Results of their locomotor responses demonstrated that valproate disrupted the development/induction and the expression of sensitization to MK-801, as it did to methylphenidate.


Haha i wonder wheter memantine sensitizes to itself.


----------



## Transform

So many posts! Do you mean you went from 250mls gbl + 300g GHB to 100mls gbl?


----------



## MeDieViL

Transform said:


> So many posts! Do you mean you went from 250mls gbl + 300g GHB to 100mls gbl?



No the other way around when i quit memantine.


----------



## Dunno

thanks for the translation ha...off to the chemist to get more robitussin tomorrow may get 3 bottles should last bout 15 days


----------



## Requiel

MeDieViL said:


> No the other way around when i quit memantine.



Excuse me if this has been asked before, but why did you quit memantine?


----------



## LoveHateLove

Has anyone seen much success in using memantine to reduce benzo tolerance?  It's been working great for stimulants, but at 20mg a day it doesn't seem to put a dent in my Valium tolerance.


----------



## MeDieViL

Requiel said:


> Excuse me if this has been asked before, but why did you quit memantine?



Money lol, altough its damn cheap when ordered online i was using high doses (60mg). And i wanted to give dxm and other stuff a try.


----------



## MeDieViL

I'm really unsure why memantine completely blocked gbl tolerance and dxm doesnt do a THING for it, i'm pretty much completely tolerant now, just get some sedation and a slight mood boost.

I saw a study how nmda antagonist number 1 prevented tolerance to social defeat induced tolerance too while number 2 didnt, however both worked for normal tolerance, so they behave differendly.


----------



## thikal

I had an idea. It certainly wrong and incorrect but: Are endogenous opiates synergies with NDMA antagonists? If yes, maybe the fast antidepressant effect of Ketamine and DXM coming from this synergy.


----------



## MeDieViL

thikal said:


> I had an idea. It certainly wrong and incorrect but: Are endogenous opiates synergise with NDMA antagonists? If yes, maybe the fast antidepressant effet of Ketamine and DXM coming from this synergie.



Doubtfull as the antidepressant effect remains after agonism, the antidepressant effects have been associated with synaptogenesis but that isnt the full story, if it was we wouldnt have to redose every week, but couldnt give a shit, better then taking shitty ssri's everyday.


----------



## MeDieViL

I really want someone to try GBL with memantine and confirm my experiences with regards to tolerance.


----------



## MeDieViL

My next test is phenibut with memantine, would be interesting if it blocks tolerance to this stuff wich has insane tolerance issues on its own.

I'm expecting it to block tolerance and also actually did see a positive anecdotal report but it was really vague, just something like "it prevents tolerance to everything i take, so i can keep taking phenibut without problems", or something like that.


----------



## MeDieViL

J Thromb Haemost. 2008 Oct;6(10):1685-92. Epub 2008 Jul 18.
Treatment with dextromethorphan improves endothelial function, inflammation and oxidative stress in male heavy smokers.
Liu PY, Lin CC, Tsai WC, Li YH, Lin LJ, Shi GY, Hong JS, Chen JH, Wu HL.
Source
Division of Cardiology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Abstract
BACKGROUND:
Dextromethorphan (DM) is reported to reduce the inflammation-mediated degeneration of dopaminergic neurons.

OBJECTIVE:
The goal of this study was to test if DM can improve the endothelial dysfunction and inflammatory markers in heavy smokers.

PATIENTS AND METHODS:
Forty habitual smoking healthy male volunteers (mean age, 31.5 +/- 1.4 years) were randomly given either DM (120 mg day(-1)) or a placebo for 6 months. We determined endothelial function using the brachial artery diameter changes in flow-mediated dilatation (FMD) and measured their inflammatory and oxidative markers. A sex-and-age matched non-smoking group (n = 20) was compared as normal parameters.

RESULTS:
Habitual smokers showed impaired baseline endothelial function in FMD (smoking vs. non-smoking: 6.3 +/- 1.8 vs. 10.2 +/- 2.3% respectively, P < 0.01). Without change in smoking behavior, lipid and metabolic parameters, a significant increase in FMD was found in the DM-treated group (32%), accompanied by a decrease in high-sensitivity C-reactive protein (hs-CRP), phospholipase A(2), matrix metalloproteinase-3, interleukin 6 (IL-6) and tumor necrosis factor-alpha receptor II (TNF-alpha RII) (all P < 0.05), but unchanged in von Willebrand factor (VWF)and plasminogen activator inhibitor-1 (PAI-1). An increase in plasma glutathione peroxidase and a decrease in spot urinary excretion of 8-epi-prostaglandin F(2a) were found in DM-treated smokers.

CONCLUSIONS:
Our study suggests that a 6-month treatment with DM can improve endothelial function and attenuate vascular oxidative stress and inflammation markers in habitual smokers.


----------



## thikal

MeDieViL said:


> I really want someone to try GBL with memantine and confirm my experiences with regards to tolerance.



I'm waiting my order, ordered yesterday so wait a few weeks!  Thanks for your explanations of my false "theorie"! :D

I'm planning to do this:
- Stop taking piracetam (i will try the piracetam+memantine combination in an other trial to see if piracetam have an impact)
- Take magnesium daily, rhodiolia rosea when i need a little more concentration
- First week: 5mg/day mementine
- 2 week: 2x5md/day memantine
- 3 week: 15mg/day Memantine
- 4 week: 20mg/day memantine
- 5 week: 30mg/day memantine
- 6 week: 40 mg/day memantine
- 7week: End of the supply, see if it worked and maybe buy some more!

At the second or third week i will pass my exams. I really don't want my mind to be fogged. Is dosage enough progressive to lessen the side effects? 

I've got huge tolerance to GBL euphoria. Took some last week and still have nothing but a fucking lethargic mood^^ I've little to medium tolerance to codeine (thanks to DXM), will see if memantine affect tramadol tolerance too. Might take MDMA or methylone in a few weeks, i'm really interested by St John Wort. Maybe i'll try it too!


----------



## MeDieViL

What substances have you found dxm ineffective for? So also does shit for GBL in your experience? 

I think the hard pain would be better and taper in a week, then after a week the adaptation period should be over, otherwise youll keep come chronic cognitive impairement altough maybe unnotacible.

I jumped from 40 to 80 in one day once with 20 grams of piracetam to buffer out any dissociation (apperantly piracetam also nearly completely antagonizes ket dissociation and stuff, so without piracetam didnt do that stunt haha).

Did dxm work for tramadol tolerance?

Ive theorised wellbutrin can help tolerance issues, however it doesnt affect GHB in my experience, butthen again that one may need memantine.


----------



## MeDieViL

DJ Revisionist said:


> I finally did MDMA for the first time since my Delsym experiment the other day. Overall, I found that there was definitely an increase in the "magic" of the MDMA and that it had more substance compared to any rolls in recent memory. Unfortunately, the MDMA I was taking wasn't the greatest quality so the roll wasn't mind blowing by any standards but it was better than the last three I've had on the same stuff. I of course didn't know there was something wrong with the MDMA until my friend who's only done MDMA once in his life also thought it was lacking in addition to a couple of experienced users thinking the same. I thought it was just my tolerance.  Increased talkativeness and musical appreciation were noted along with an intensification of visuals such as words appearing in gravel and faces morphing. My initial results seem promising but obviously more trails will have to be done before any conclusions can be made. Stay tuned next month.


Interesting we need some more mdma experience, and ppl here posting that everyone here complaining about tolerance needs some fucking cough syrop.


----------



## MeDieViL

What is interesting is that with stims GBL is still as euphoric, maybe doses higher never pay attention to that, just keep dosing till im good, but on its own its just a mild mood boost, and more sedation and then knock out range.


----------



## rickolasnice

MeDieViL said:


> My next test is phenibut with memantine, would be interesting if it blocks tolerance to this stuff wich has insane tolerance issues on its own.
> 
> I'm expecting it to block tolerance and also actually did see a positive anecdotal report but it was really vague, just something like "it prevents tolerance to everything i take, so i can keep taking phenibut without problems", or something like that.



I'm on it! (kinda)..

Carrying on from my other thread.. i had 300mg last night before bed, 300mg this morning at about 7am and another 300mg at about 10am.. that makes 900mg which i'm gonna try and keep it at for the day (normally this would be kinda uncomfortable).. just took ~50mg DXM about an hour ago.. let's see if i can come off phenibut within 4 days 

I'm kinda hoping your experience is based around GHB receptors rather than GABAb (for selfish reasons )


----------



## thikal

MeDieViL said:


> What is interesting is that with stims GBL is still as euphoric, maybe doses higher never pay attention to that, just keep dosing till im good, but on its own its just a mild mood boost, and more sedation and then knock out range.




I most agree with you! (don't sure if my sentence is correct grammatically... anyway) Take GBL and stimulants greatly increase the "body high euphoria". I'm fucking in love with this effect. You can use far more GBL without pass out. 
When i take GBL alone now, it come without any euphoria at all, but mix GBL with stims make the euphoria come back (a little if you have huge tolerance!) (just coffee can enhance GBL a bit).  

For tramadol+DXM: I was particularly vigilant because of the risk of serotonin syndrome. Never took more than 90mg of DXM in 8 hour during this combo. I think that under this dosage, the risks are greatly reduce. I can say that it increase opiate effect, but in the third time had some headache and stopped all experiments fear of bad interaction. Don't advise this mix at all!

Phenibut: Bought some a few months ago. Didn't feel anything under 4,5g. Suspected a cross tolerance with GBL. I'm interested to let an other chance if memantine can decrease tolerance. Ohoh and i tried rectal administration, toooo acid, hurt bad! 

DXM is useless for GBL tolerance, but 60mg when you feel anhedonic put you in a greater mood (according to me and my girlfriend).



> I think the hard pain would be better and taper in a week, then after a week the adaptation period should be over, otherwise youll keep come chronic cognitive impairment although maybe unnoticeable.
> 
> I jumped from 40 to 80 in one day once with 20 grams of piracetam to buffer out any dissociation (apparently piracetam also nearly completely antagonizes ket dissociation and stuff, so without piracetam didn't do that stunt haha).



So do a thing like that?
- 1 day 5mg
- 2 day 10mg
- 3 day 15mg
-.4 day 20mg 
- 5 day 30mg
- 6 day and other 40mg

Don't want to turn into a fucking "will-o'-the-wisp"during my exams like the last time with miss' saly  ^^ I've pirarectam too.


----------



## MeDieViL

@thikal

I'm a bit more risky when it comes thx for posting your results mate. I ghink il just  keep cyprophetradine nearby, wich  usually do intill i results and the forget to sthei finest and stuff.


----------



## MeDieViL

thikal said:


> So do a thing like that?
> - 1 day 5mg
> - 2 day 10mg
> - 3 day 15mg
> -.4 day 20mg
> - 5 day 30mg
> - 6 day and other 40mg
> 
> Don't want to turn into a fuNo really exactly like that, some weekks i wasnt around joor juumrto: for ro to the other haha.cking "will-o'-the-wisp"during my exams like the last time with miss' saly  ^^ I've pirarectam too.$ (i ment poor a adcha,ce where i still had roghings like other christs.)
> $
> 
> Hahahaa this is awesoeme


I advice a apartement realsoon if you get one for a good price haha, poor on mijlij maar datwas mij omgeving altijd am geweest, anders was het niet chronisch, ben er 99% zeker geweest.


----------



## MeDieViL

> I'm fucking in love with this effect. You can use far more GBL without pass out.


Yeah man, just dose up enoughand you dont od theng fo inthe far.. Offcourse there's a limit, haha.

The next few months we sould knox for englisch.

The drugs tonight will good.


----------



## ferinox

The dxm I use seems to work really well with hydrocodone. I only have to increase the dose very rarely to maintain euphoric effects. When I take oxycodone or oxymorphone, my tolerance still seems to go up pretty fast though. From my experience it's still slowing down the buildup over not taking dxm but not enough. Does hydrocodone build tolerance more slowly or is it all in my head?


----------



## thikal

> Yeah man, just dose up enoughand you don't od theng fo inthe far.. Off course there's a limit, haha. The next few months we sould knox for englisch.



Od when the stim goes down you mean? Stop taking or slow down G before the end of your stims stocks! 

KnoX for English? Didn't understand all sorry^^ You use words that aren't in the dictionary mate! Think to these poor no-anglophone


----------



## MeDieViL

I had a psychotic episode last weekend, i apoligize for any of my last posts that are complete jibberish.


----------



## retard

So MeDieViL, what is the best short acting NMDA antagonist unlike memantine against tolerance? 
I had good experience with memantine with want to try something else for testing.


----------



## MeDieViL

Acamprosate


----------



## thikal

MeDieViL said:


> I had a psychotic episode last weekend, i apologize for any of my last posts that are complete gibberish.



I don't care man, you are so interesting all the time, just take care of your health please. I mixed 60mg of DXM and 4 or 5 piece of space cake a week ago, oh fuck not a bad trip but there was some fucking synergy. Too much hallucinations in the dark, i had to put a night light on my bedroom, my girlfriend was laughing at me to death hehe. I don't like at all to mix THC and DXM usually, it wasn't an exception...

Will start memantine on a few days i hope. But fight against tolerance can push psychologic dependence to the roof in an other hand  isn't it? are NDMA antagonists fight against craving too? Hehe i'm full of questions, i apology 

You said on an other board that memantine has an effect on tolerance to drugs that have an effect on GABA, nicotinic receptors, dopamine... Do memantine act on GHB receptors too? Full GHB effects all the time, i can't imagine that without something wrong... Can't believe it, too beautiful^^ Anyway, will have memantine in a few hours!


----------



## thikal

Strange, my memantine's tablets name is "admenta" instead of Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Memox by Unipharm. Can it be a fake imitation?

Started my experiment today at 10mg/day.

EDIT: It is the third time I read all this thread and... It makes me damn wet like a little pussy all times hehe! This thread have major CNS stimulation in me, and a bit manic too I confess... :D

EDIT2: And did some crazy folk tried memantine and salvia? Already tried salvia (extremely low doses, like a little puff) and DXM (second level) and it was pretty intense compared to the low quantity I took!



> After some serious problems with Oxy and Bupe, im free from opiates. it was kinda simple in the end. from 300-800mg oxy most days, then 10mg bupe day 1 with 500mg Dxm (it was a bad day) and 2mg xanax. Next day 2mg bupe plus 1000mg dxm. days 3,4,5 with 2mg Bupe 1500mg of DXM and 2mg Xanax. Day 6, 7 1000mg dxm and no bupe, xanax to taste with only 10 left. finished the rest of the DXM off (*started with 25 500mg capsules)* and the xanax over 7 days and then nothing. 1st night no sleep and desperate for something, but defenitely no sickness, no throwing up. Writing and drawing (things i dont normally do) helped thru the bad parts.
> 
> ]
> does anyone else have good experience in this way? I found theres no withdrawal (for me at least) no matter how high you go, *just boredom when the closed eye visuals stop *


Hahaha entertaining!

Two beers and i'm reallly happy, memantine work well!


----------



## MeDieViL

Keep the updates coming guys

On another board someone mentione that memantine appeared to work against phenibut tolerance. lol salvia, makes we wonder what other crazy substances we may be able to stop tolerance too haha.


----------



## crOOk

After having been off dxm for 6weeks, I can't shake the feeling that tolerance is developing much faster now. Mind you I was anticipating this, so my judgement might be clouded (it always is clouded anyway due to the psychotropic substances in my bloodstream lol).
I used to have 100ml of liquor and would be drunk, within 2 weeks after quitting the DXM (~30-90mg ~eod) I found myself killing 280ml of pure ethanol (in the form of gin/bourbon/rum) per day without getting drunk. Never had been abusing booze like that before. Also the pot tolerance seems to have increased slightly while my amp tolerance seems to be constant at a relatively low level: 150mg ~20% oral amphetamine phosphate salt (+maybe some other salt) in the a.m. Opioids started to have less of an effect without dxm as well, though this might be due to more frequent use as of late.

Just thought I'd share my feeling with you guys, take it all with a grain of salt though. It's just something to consider, something to observe if you're taking nmda-antagonists for tolerance control. I'd be surprised if some sort of rebound effect like up regulation of AMPA/NMDA receptors wasn't developing with frequent NMDA antagonist use.


----------



## Jackinbox

Assuming about 40-60 mg a day, memantine is quite expensive.  I can't report any side effects on memantine (except when titrating) up to 40 mg (and maybe even 60).  Over-the-counter DXM is even more expensive. Magnesium is cheap but nobody report positive results. 

I need about 20 mg of dexedrine a day to be fully functionnal but need to take a lot of breaks of it so I'm not really functionnal. I don't know if it's the tolerance or if I'm just getting more tired (and usually end up sleeping almost all day multiple time per weeks). 

I tried 120 mg of DXM today along my 150 mg of Lyrica. I didn't feel anything  for hours until I decided to take 5 mg of dexedrine. I got the "feel good" effect of dexedrine but without anxiety. 5 mg is usually not enough there is a synergy going on, I guess. 

I see that some website sell bulk DXM. Anyone ordered DXM on the Internet? 

How much of an issue tolerance to DXM is?


----------



## superluminality

I've made an interesting discovery by combining high doses of L-Theanine (itself an NMDA antag) 300-600mg at a time with the usual dose of DXM (the  equivalent of 60mg at a time, half HBr and half Polystirex) and lots of magnesium citrate (600mg-1g). The Theanine massively potentiates the DXM to the point where on the first night I tried the combo with my usual dose of Marinol (45mg), I found myself borderline 'tripping' from a mere 60mg DXM!

This combo seems to work far better than any of them alone, though the magnesium may or may not be a necessary element.

Aside from excessive salivation (hardly a big deal), this combo has produced no negative side effects of any kind and seems to be working better than  my previous efforts using these three NMDA antagonists separately or in combination but with lower doses of Theanine, which seems to be the key here. Once I started reading, I discovered that there are many reports here on BL of Theanine hugely potentiating other things, notably DXM.


----------



## crOOk

Pharmacies over here sell dxm at 3€ for 20x30mg which isn't really all that much. Go see if you can order it from a German online pharmacy. Hope this doesn't count as source discussion since it's legal otc medication (which I feel is gonna change very soon).

edit: one of my all time favourite threads! :D


----------



## thikal

I'm at 20mg memantine /day. Tried GBL yesterday and was disapointed. I wasn't especting all my tolerance to drop in one week at 20mg, Will try at 40mg/day anyways! Have a nice day guys (and girls)



> edit: one of my all time favourite threads!


This thread is like when you are in the childhood and someone say to you "you can eat all this candy and chocolate and never being sick!" But don't forget that moderation is the key!


----------



## MeDieViL

thikal said:


> I'm at 20mg memantine /day. Tried GBL yesterday and was disapointed. I wasn't especting all my tolerance to drop in one week at 20mg, Will try at 40mg/day anyways! Have a nice day guys (and girls)
> 
> 
> This thread is like when you are in the childhood and someone say to you "you can eat all this candy and chocolate and never being sick!" But don't forget that moderation is the key!



Thx for your update, still gotta respond to your pm srry for stalling so much.

I think i was taking 30mg memantine a day when i took 100ml of GBL a week without any tolerance, definatly more then 20mg tough, also for amp tolerance it seems it only really works well at 30mg or more.


----------



## MeDieViL

Jackinbox said:


> How much of an issue tolerance to DXM is?



NMDA receptors do upregulate in response to nmda antagonists however this is limited, they wont upregulate for 100% so they will allways stay functional and work for drug tolerance, the only issue may be rebound accelerated tolerance after you stop taking them untill they are back downregulated.


----------



## thikal

MeDieViL said:


> Thx for your update, still gotta respond to your pm srry for stalling so much.
> 
> I think i was taking 30mg memantine a day when i took 100ml of GBL a week without any tolerance, definatly more then 20mg tough, also for amp tolerance it seems it only really works well at 30mg or more.



No worries  Yes I understood that the problem was the low dose memantine. (I wanted to try at different dosage, and you are right when you say that 20mg/day isn't enough to block/reverse tolerance totally, in me!) Tomorrow, after my last fuck*** exam will increase dosage to 40mg/day. 

Actually, I feel a bit slow (bought a box of codeine 2 days ago and I gave half the money needed and waited like a fool in the clouds^^) but this is easy fixed with some running and piracetam. I definitely feel some mood lift, but not all the time it's funny (I'm not depressive so it's difficult to say)

Does somebody know if I will be hurl in the sky with low  doses AMT or 2C-D and 40mg memantine/day in the blood? I'm not an experienced psychonaut yet so I'm a bit afraid by some unexpected potentialisation, I fear for my poor ass hole hehe^^


----------



## MeDieViL

Hurl in the sky? gues you mean in a differend world or something, but you should be fine, depends on what you want to take 2CD for, i used to take it in low doses, like 10mg i think where it just gave me euphoria, amazing synergy with GBL btw, was taking the g, 2CD combo every evening for a week or 2 weeks where it gave me mdma like euphoria without any mania (wasnt acting weird like high on amp or mdma) was also on memantine.

I cant promise you memantine will reverse tolerance too to gbl, just know it prevented it from occuring for me in the past, there's a chance it would also reverse it but il have to wait for your experience first.


----------



## thikal

MeDieViL said:


> Hurl in the sky? gues you mean in a differend world or something, but you should be fine, depends on what you want to take 2CD for, i used to take it in low doses, like 10mg i think where it just gave me euphoria, amazing synergy with GBL btw, was taking the g, 2CD combo every evening for a week or 2 weeks where it gave me mdma like euphoria without any mania (wasnt acting weird like high on amp or mdma) was also on memantine.
> 
> I cant promise you memantine will reverse tolerance too to gbl, just know it prevented it from occuring for me in the past, there's a chance it would also reverse it but il have to wait for your experience first.




Yes shot in the sky, tripped to death, I don't know, "perché a mort"^^ Anyways you understood  Hohoho really interested by what you said with your 2CD and GBL combo, will try it soon! For GBL, i used it far too much and lost all the euphoria. Yesterday, took 3 doses and at the last one I was put again in a dirty mood, but I had to take just 1,6mL instead of 2,8 few mouths later. I will report if euphoria came back at 40mg memantine. I hope so if it can work with benzos, might take some time, the junky speculation/hope hehe. If not, I will order some more and try 80mg like you  I want to be totally intolerant :D


----------



## MeDieViL

Hopefully it will work as well for you as it did for me, every evening it was like mindblowing euphoria and at the morning you woke up without any comedown, just refreshed like you didnt take anything lol.

Haha well the one that tries is the one that wins.


----------



## thikal

MeDieViL said:


> Hopefully it will work as well for you as it did for me, every evening it was like mindblowing euphoria and at the morning you woke up without any comedown, just refreshed like you didnt take anything lol.
> 
> Haha well the one that tries is the one that wins.



Sound fucking great hehe! My girl friend already hate you because I:


> speak too much on stupid combos and NDMA bullshit





Magikal kat if you're still here, can you develop mixing memantine and DXM? Memantine dosing all the time, and DXM to add when you take too much of a dope in few times? You said that they work differently, combining two different mechanisms MIGHT create a synergy to decrease tolerance?

In my next memantine order I will ad some acamprosatet

Such a beautiful synergy with G and 2C-D, music sound extremely great, vivid. Great combo, thanks mate for the tip hehehehe love you already


----------



## MyDoorsAreOpen

superluminality said:


> Personally, I've made an interesting discovery by combining high doses of L-Theanine (itself an NMDA antag) 300-600mg at a time with the usual dose of DXM (the  equivalent of 60mg at a time, half HBr and half Polystirex) and lots of magnesium citrate (600mg-1g). The Theanine massively potentiates the DXM to the point where on the first night I tried the combo with my usual dose of Marinol (45mg), I found myself borderline 'tripping' from a mere 60mg DXM!
> 
> This combo seems to work far better than any of them alone, though the magnesium may or may not be a necessary element.



Thanks a lot for this! I've tried combining 200mg L-theanine with 60mg DXM, then a hit of marijuana, and found this a very enjoyable and therapeutic combination. I'd love to see a clinical trial of this combination (minus the marijuana) for major depression.

60mg seems to be something of a 'sweet spot' for DXM, I've discovered. It's the highest dose at which I feel perfectly functional, and get no negative aftereffects, but the lowest dose at which I feel some mental effects from it. I actually can study on this dose, and hold onto the material quite well. (On 90mg, forget about it!).

Adding the theanine makes the DXM feel a bit more like very low dose ketamine. I think this is not only the added NMDA antagonism, but also the fact that, just like k, theanine enhances dopamine, which DXM doesn't.

At higher (reacreational or visionary) doses of DXM, I've experienced an absolutely amazing afterglow, that feels somewhat like low-dose amphetamine, followed by a crash, that leaves me emotionally flattened an depressed, not unlike an amphetamine crash. My working theory is that high-dose DXM upregulates DA receptors so much (the afterglow), that it precipitates a rebound downregulation (the crash), leaving your CNS with lower DA tone than before taking DXM, and defeating the whole purpose of taking DXM as a DA enhancer.

This is getting a bit off topic, but I'm finding more and more that my dopamine system can't be cheated. Increasing my dopaminergic tone far above its natural set point, no matter the mechanism (amphetamines, NMDARAs, DA precursors, etc.), will inevitably lead to my body yanking those DA receptors and leaving me in an anhedonic state. Perhaps 60mg of DXM is just below the threshold of DA enhancement where this rebound downregulation happens.


----------



## MeDieViL

thikal said:


> Such a beautiful synergy with G and 2C-D, music sound extremely great, vivid. Great combo, thanks mate for the tip hehehehe love you already



Haha that combo is fucking win, and with mem you can take it like on a regular basis, kinda simular as G, theres pretty much no comedown and shit, its like amazing stuff haha


----------



## MeDieViL

A mate of me using a combination of memantine, DXM and acamprosate for amphetamine tolerance, and just noted that after he ran out of acamprosate, tolerance started developping to amp faster, it seems they all synergise, so im going on a simular combo and experiment a bit with this. Ive restarted memantine yesterday, added in DXM today, will add in acamprosate when i'm back home (currently with the girlfriend).

Also i think im noting some G tolerance reversal but its only minimal, will need to raise he mem dose for some better effects i think (currently at 20mg mem a day and 60mg DXM 3 times a day).


----------



## MeDieViL

I gues ill add in theanine too looking at the positive reports.


----------



## MeDieViL

MyDoorsAreOpen said:


> Thanks a lot for this! I've tried combining 200mg L-theanine with 60mg DXM, then a hit of marijuana, and found this a very enjoyable and therapeutic combination. I'd love to see a clinical trial of this combination (minus the marijuana) for major depression.
> 
> 60mg seems to be something of a 'sweet spot' for DXM, I've discovered. It's the highest dose at which I feel perfectly functional, and get no negative aftereffects, but the lowest dose at which I feel some mental effects from it. I actually can study on this dose, and hold onto the material quite well. (On 90mg, forget about it!).
> 
> Adding the theanine makes the DXM feel a bit more like very low dose ketamine. I think this is not only the added NMDA antagonism, but also the fact that, just like k, theanine enhances dopamine, which DXM doesn't.
> 
> At higher (reacreational or visionary) doses of DXM, I've experienced an absolutely amazing afterglow, that feels somewhat like low-dose amphetamine, followed by a crash, that leaves me emotionally flattened an depressed, not unlike an amphetamine crash. My working theory is that high-dose DXM upregulates DA receptors so much (the afterglow), that it precipitates a rebound downregulation (the crash), leaving your CNS with lower DA tone than before taking DXM, and defeating the whole purpose of taking DXM as a DA enhancer.
> 
> This is getting a bit off topic, but I'm finding more and more that my dopamine system can't be cheated. Increasing my dopaminergic tone far above its natural set point, no matter the mechanism (amphetamines, NMDARAs, DA precursors, etc.), will inevitably lead to my body yanking those DA receptors and leaving me in an anhedonic state. Perhaps 60mg of DXM is just below the threshold of DA enhancement where this rebound downregulation happens.


Does this crash also occur if you keep on taking a NMDA antagonist? Like would it be possible to take a recreational dxm dose, upregulate dopamine quite a bit, and then "lock" that upregulation with a proper daily nmda antagonist regime.


----------



## thikal

I took a tablet of 200mg tramadol (not the instant realise but the "long release", I don't know the write word sorry) to lessen the little crash of MDPPP  (an excuse to take some opiate hehe). I felt a great mood lift thanks to tramadol like I didn't feel yet at this dosage. I used to take more than 700mg tramadol IR and just don't really feel euphoria, 200mg tramdol "long realise" never felt that way. Beautiful, beautiful...

 I think that memantine or an other NDMA antagonist is a nice weapon to prevent dependence occurring! A beautiful reduction risk tool! Harm reduction power!



> A mate of me using a combination of memantine, DXM and acamprosate for amphetamine tolerance, and just noted that after he ran out of acamprosate, tolerance started developping to amp faster, it seems they all synergise, so im going on a simular combo and experiment a bit with this. Ive restarted memantine yesterday, added in DXM today, will add in acamprosate when i'm back home (currently with the girlfriend).
> 
> Also i think im noting some G tolerance reversal but its only minimal, will need to raise he mem dose for some better effects i think (currently at 20mg mem a day and 60mg DXM 3 times a day).


Thanks for the info! I feel some potential here!


----------



## MeDieViL

Ive also got tramadol's long release at home, still dont really understand them tough, have got the impression they constantly release a bit and arent like the amp long release things that release a second dose several hours later? Also what is the max dose of the trams slow release, is it also 400mg and after that you go over the seizure treshold? Ive got benzo's now (the beatifull etizolam to be exact, the only benzo that actually synergizes with stims, kinda like g instead of making me stumble around and letting me feel like i took a lower dose of stims like all other benzo's). enough rambling, just didnt find a clear answer with searching online haha.

Also it was recently discovered tramadol wasnt a ssri but a serotonine releaser, dxm appears to synergize with mdma, would be cool if we disover the same of dxm haha, because it doesnt inhibit mdma like prozac and co i think it MIGHT be a possibility, haha enough of my wishfull thinking.
DXM is interesting stuff anyway.


----------



## thikal

I think I'm actually tripping a little bit on memantine. Coudn't take my dosage yesterday and took 40mg 5 hours ago. (it was the second day on 40mg). I took 200mg tramadol and 300mg codeine for a nice opiate buzz, but the buzz isn't opiate like hehe. Not in a badway anyways, feel really good, heard some strange noise all the time, I think it's the little dissociation. I took some piracetam too see if the effects decline (don't want the effect to go down, but it's for science haha :D )


----------



## superluminality

thikal said:


> I think I'm actually tripping a little bit on memantine. Coudn't take my dosage yesterday and took 40mg 5 hours ago. (it was the second day on 40mg). I took 200mg tramadol and 300mg codeine for a nice opiate buzz, but the buzz isn't opiate like hehe. Not in a badway anyways, feel really good, heard some strange noise all the time, I think it's the little dissociation. I took some piracetam too see if the effects decline (don't want the effect to go down, but it's for science haha :D )



Interesting....it was/is my impression that the *-racetams hold the potential to *increase* opioid tolerance (possibly also some others such as benzos, but probably not to, say, amphetamines or methylphenidate).....watch those combos carefully, lots of unexplored terrain there -- which means both great potential and great risk.....


----------



## MeDieViL

thikal said:


> I think I'm actually tripping a little bit on memantine. Coudn't take my dosage yesterday and took 40mg 5 hours ago. (it was the second day on 40mg). I took 200mg tramadol and 300mg codeine for a nice opiate buzz, but the buzz isn't opiate like hehe. Not in a badway anyways, feel really good, heard some strange noise all the time, I think it's the little dissociation. I took some piracetam too see if the effects decline (don't want the effect to go down, but it's for science haha :D )



Your in the adaptation phase mate, it can make you a little dissociated or act weird because of bad brainfog haha but should pass soon, piracetam MAY interfere with its tolerance property's however it does work good to buffer out the initial side effects, i jumped from 40 to 80mg mem once in one day with 20 gram piracetam to buffer out the dissociation lol (dont try at home). Mem still gave me double vision at first and made me dizzy, in the end had to cut down to 60mg tough (wich actually turned out to be a wonderfull dose for me).


----------



## MeDieViL

superluminality said:


> Interesting....it was/is my impression that the *-racetams hold the potential to *increase* opioid tolerance (possibly also some others such as benzos, but probably not to, say, amphetamines or methylphenidate).....watch those combos carefully, lots of unexplored terrain there -- which means both great potential and great risk.....



We know the racetams initially greatly potentiate many drugs and bring tolerance back down, however on the racetams tolerance develops as fast again as without them, so they are like a temporary solution, i would be interested to see how they play out long term with nmda antagonists, its indeed unexplored domain, with their positive modulation of NMDA, there's indeed great potential but also great risk.


----------



## thikal

I never felt that piracetam decrease tolerance to any drugs. It's really great when you coming down stimulant binge, but I didn't feel that it potentiate them (according to me). 

Oh and the adaptation phase is a nice feeling, I just have to take low dose of some random opiate to potentiate the "adaptation phase" effetcs hehe. I feel baseligne this morning anyways, it's end^^


----------



## thikal

superluminality said:


> Heh, you guys are seriously making me drool in anticipation of trying Memantine....and that's not just the Theanine hypersalivation!



It wasn't the adaptation phase end when I write this, I was wrong^^ Today I'm still a little bit weird/stupid/feel little drunk. Piracetam at 1g fix nothing to this (and I don't want to eat 10g of this nasty stuff god not!). I will try GBL again tonight, hope more euphoria than the other time! Will mix it with some squeegee (Is it the write word?), I'm exited. Did you ever vomit chese fondue? Not? Lot of fun hehe, it's like a rope when you throw it.


----------



## Wizzle

Maybe act a little confused, in combination with the drooling you might be able to score some memantine from your own physician


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## MeDieViL

Guys, we also shouldnt forget that amisulpiride upregulate GHB receptors (combined with agonism) this may be perhaps an essential addition for those focussing on vitamine G.


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## MeDieViL

Today upped my memantine dose to 40mg and also added acamprosate to my regime, might take a break of DXM, to see how much extra benefits it would provide.

One time for sure, memantine is working amazing allready for stim tolerance, effects ive never manged to pull of with DXM or acamprosate on their own, i do think they cna be good augmenters, nonetheless DXM on its own can work perfectly fine for other individual.


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## MeDieViL

By accident i took 60mg DXM this morning after wich i combined it with 120mg 5APB, didnt notice any effects of serotonine syndrome (wich may be caused by memantine, wich has a protective role) still there appeared to be synergy and in general ppl dont report the same blunting response as adding dear prozac to our happyness pill, well maybe thats another indication that DXM might be a serotonine releasing agent, definatly take this post not serieusly of me tough as it without doubt can end DEADLY, but if like to hear some other opinions on this subject.


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## chaos_destroy

^I imagine at those sort of low doses of DXM that risk of serotonin syndrome would be quite low anyway right?


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## MeDieViL

There should still be plenty of mdma supression occuring, anyone knows any more reports about this combo, mostly ive read that dxm potentiates mdma by those few that combined them.


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## MeDieViL

I gotta say that memantine works FAR better then DXM or acamprosate, noticing some major benefits with dxm or acamprosate on their own never really gave me, i do think those 2 can be perfect augmentors to make mem more effective.

Il elaborate more later.


----------



## MeDieViL

chaos_destroy said:


> ^I imagine at those sort of low doses of DXM that risk of serotonin syndrome would be quite low anyway right?



Speaking of that, i think i remember reading that memantine can supress serotonine syndrome in a rodent study's, not sure wheter that doses were very relevant for us tough, need to dig those up again, after wich well start our next quest, figuring out what memantine doesnt help with haha.


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## MeDieViL

> Levorphanol
> From Wikipedia, the free encyclopedia
> Levorphanol
> 
> Systematic (IUPAC) name
> 17-methylmorphinan-3-ol
> Identifiers
> CAS number	77-07-6
> ATC code	None
> PubChem	CID 5359272
> DrugBank	APRD00764
> ChemSpider	16736212
> UNII	27618J1N2X
> KEGG	D08123
> ChEMBL	CHEMBL651
> Chemical data
> Formula	C17H23NO
> Mol. mass	257.371 g/mol
> SMILES	eMolecules & PubChem
> InChI[show]
> Pharmacokinetic data
> Bioavailability	70% (oral); 100% (IV)
> Protein binding	40%
> Metabolism	Hepatic
> Half-life	11-16 hours
> Therapeutic considerations
> Pregnancy cat.	C
> Legal status	Controlled (S8) (AU) Schedule I (CA) Schedule II (US) Class A (UK)
> Dependence liability	High
> Routes	oral, intravenous, subcutaneous, intramuscular
> (what is this?)  (verify)
> Levorphanol (Levo-Dromoran) is an opioid medication used to treat severe pain. It is the laevorotary stereoisomer of the synthetic morphinan (Dromoran) and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic. Morphinan is the parent drug and prototype of a large series of opioid and/or NMDA antagonists and opioid agonists used in medicine including nalbuphine, butorphanol, dextromethorphan, and others.
> Levorphanol labeled with tritium was used in the research which led to the discovery of opioid receptors in the human nervous system, including the first study published in 1971.[1]
> Levorphanol has the same properties as morphine with respect to the potential for habituation, tolerance, physical dependence and withdrawal syndrome. It is 4 to 8 times as potent as morphine and has a longer half-life. Approximately 30 mg of oral morphine is roughly equianalgesic to 4 mg of oral levorphanol.[2] The laevo isomer is the source of the narcotic properties of the racemic drug Dromoran, but the dextro isomers are also useful in medicine: in addition to acting on sigma receptors, the O-methyl derivative of its dextrorotary isomer, dextromethorphan, is a common NMDA receptor antagonist and pro-drug to dextrorphan.[3] Oral doses of levorphanol come in 2 mg and 4 mg strengths or subcutaneous injection every 6 to 8 hours.
> Levorphanol has affinity to μ, κ, and δ opioid receptors, but lacks complete cross-tolerance with morphine. The duration of action is generally long compared to other comparable analgesics, and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favourable of the strong narcotics. Its NMDA actions, similar to those of the phenylheptylamine open-chain narcotics such as methadone and ketobemidone, make levorphanol useful for types of pain that other analgesics may not be as effective against; levorphanol's sigma receptor, SNRI properties make it even more useful particularly for neuropathic pain.[4]


The best thing i can come up with right now dextromethorphan is pretty closely related to levorphanol.


> Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol, an opioid analgesic.



And what do we know of opiates? They are serotonine releasers in several brainarea's, so in my opinion, it might be quite possible DXM is a releasing agent.

However ive just posted some really lose connections, and my knowlmedge is pretty limited on this, so definatly cant make a conclusion for sure, just hoping this would sparkle a interesting discussion.



> Bull Exp Biol Med. 2007 Aug;144(2):210-3.
> Self-administration of morphine by rats causes monoamine release in the anterior cingulate cortex.
> Sudakov SK, Rusakova IV, Trigub MM, Kudrin VS, Klodt PM.
> Source
> National Research Center of Narcology, Federal Agency for Health Care and Social Development. s-sudakov@mail.ru
> Abstract
> Monoamine content in the microdialysate from the anterior cingulate cortex was measured in rats after injections and self-administration of morphine. Forced intraperitoneal injection of morphine did not lead to appreciable changes in the monoamine levels in the dialysate. Self-administration significantly increased monoamine levels in the extracellular space of the anterior cingulate cortex. Changes in catecholamine levels in the extracellular space of the anterior cingulate cortex correlated with the intensity of self-administration. The more morphine the animals injected to themselves, the greater was the increment in dopamine and norepinephrine levels. It seems that the increase of serotonin content in the anterior cingulate cortex did not depend on blood morphine concentration, but just reflected the fact of narcotic self-administration. The release of serotonin from nerve endings in the anterior cingulate cortex gradually increased at the beginning of the session, after which serotonin concentration started to decrease. The results indicate that monoamines are released from nerve endings in the anterior cingulate cortex only in response to self-administration of morphine. Catecholamines were released after each self-administration of the narcotic, while serotonin release seemed to be associated with the general status of the animal realizing this behavior.





> Synapse. 2005 Apr;56(1):29-38.
> Dopamine and serotonin release in dorsal striatum and nucleus accumbens is differentially modulated by morphine in DBA/2J and C57BL/6J mice.
> Fadda P, Scherma M, Fresu A, Collu M, Fratta W.
> Source
> Department of Neuroscience and Centre of Excellence Neurobiology of Dependence, Cittadella Universitaria, S.S. 554, 09042 Monserrato, University of Cagliari, Italy. pfadda@unica.it
> Abstract
> Numerous studies have demonstrated that genetic factors significantly influence opioid ability to induce behavioral modification in mice. This differential sensitivity has been extensively studied, particularly in the DBA/2J and C57BL/6J strains. In the present study, using the "in vivo" microdialysis technique in these strains, we investigated the effect of morphine administration on the extracellular levels of dopamine (DA), serotonin (5-HT), and their metabolites in the nucleus accumbens and dorsal striatum--areas thought to be involved in morphine-induced locomotor hyperactivity. In the nucleus accumbens, morphine (20 mg/kg) significantly increased extracellular levels of DA in both strains. However, in dorsal striatum the morphine-induced increase of extracellular DA was lower in DBA/2J mice than in C57BL/6J. Moreover, morphine significantly stimulated 5-HT and 5-hydroxyindolacetic acid (5-HIAA) release both in nucleus accumbens and dorsal striatum of C57BL/6J mice, whereas it decreased 5-HT release without modifying 5-HIAA levels in DBA/2J mice. These results suggest that the different behavioral and biochemical responses to acute morphine described in these two strains could be mediated by different sensitivity of both the dopaminergic and the serotonergic systems.


----------



## MeDieViL

Oh yeah, this was the study i was referring too.


> Pharmacopsychiatry. 2004 Mar;37(2):57-62.
> Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome.
> Nisijima K, Shioda K, Yoshino T, Takano K, Kato S.
> Source
> Department of Psychiatry, Jichi Medical School, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan. psychiat@jichi.ac.jp
> Abstract
> BACKGROUND:
> Serotonin (5-HT) syndrome is the most serious side effect of antidepressants. Although several drugs have been used for the treatment of 5-HT syndrome, a universal pharmacotherapy has not been established. NMDA receptor antagonists have been reported to have neuroprotective effects. In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model.
> 
> METHODS:
> 5-Hydroxy-l-tryptophan (100 mg/kg) and clorgyline (2 mg/kg) were administered intraperitoneally in rats to induce 5-HT syndrome. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior hypothalamus were measured using a microdialysis technique.
> 
> RESULTS:
> In the group pretreated with saline, the rectal temperature increased to more than 40 degrees C, and all of the animals died within 90 min of the drug's administration. The NA and 5-HT levels in the anterior hypothalamus increased to about 15- and 1100-fold of the pre-administration levels, respectively. Pretreatment with risperidone (0.5 mg/kg) and ketanserin (5 mg/kg) prevented the development of hyperthermia and the increase in the NA level. Memantine (10 mg/kg) and MK-801 (0.5 mg/kg) also prevented the development of hyperthermia and the increase in the NA level. These results suggest that NMDA antagonists, as well as potent 5-HT (2A) antagonists, may be effective drugs for the treatment of 5-HT syndrome.
> 
> CONCLUSIONS:
> Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.


----------



## thikal

MeDieViL said:


> Guys, we also shouldnt forget that amisulpiride upregulate GHB receptors (combined with agonism) this may be perhaps an essential addition for those focussing on vitamine G.



Really interesting but Amisulpiride as to much side effects on his one for me to add to my decrease tolance stack. Don't want to become a fatty impotent zombi just for more euphoria when I take some G! 8( Anyways, I'm on 40mg memantine during 3-4 days ago and at this dose it lessen greatly sides effects of GBL in me. I'm not any more in a shitty mood 2h after some G. Maybe euphoria will come back later.


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## MeDieViL

For me the biggest issue of G is that it gives me horrible brainzaps or even absence seizures (harmless seizures, but yeah the last thing you want), i went to 40mg of memantine yesterday, went back home dont have any g here atm but will try it soon.

Thats definatly a good sign, looks like we may be on the right track, just hope i can get rhid of those brainzaps and seizures as now i can only take G with etizolam or other benzo's, wich damen convulsant activity (brainzaps are basicly realy mild seizure activity, same as when you get them after mdma, serotonine receptors play a role in regulating seizure activity.

Ive added 333mg acamprosate to my regime 3 times a day, definatly notice a synergy with memantine, atleast with stims added, gives it an anxiolytic feel and feels like it perfectly synergizes with mem.


----------



## Limpet_Chicken

Acamprosate is not a typical NMDA antagonist. It is an antagonist at the polyamine binding site of the NMDAr, not the phencyclidine binding site, glycine site, glutamate (competitive) binding site or the binding site of channel blockers.


----------



## thikal

So I had the first methylone experience on memantine two days ago. 

Substances I took before the experience:
- 40mg memantine / day
- piracetam
- choline
- a multivitamin tab
- some fish oil
- a huge glass of sprem 
- magnesium citrate
(Spot the odd one out)

I didn't took an empathogen for 2 months before the experience, took like 200mg of MDPPP a week before. On the morning before methylone, I eat (10mg) and smoke (like 5mg but I don't know to chase the dragon well, there was waste) of AMT with little results. Two glass of wiskey killed all the AMT effect but it can be a facter anyways.

T0= 100mg methylone (at midnight)
T+45min = 100mg methylone
T+1h45 = 50mg methylone
T + 2h45 = 20md 2C-D

Before the 2C-D, I had real great time because of the quality of methylone (didn't have methylone of this quality for like one year on a half, but think memantine is a huge facter here). When I took this 2C-D, whow I instantly loose all track of the time and took a HUGGGGGE rolling right on my fucking face. I told my frend to get ready to phone help because I thought I was overdosing severly. Now I think my vital signs weren't frightening, no scaringly fast heartbreath (maybe a little bit but it's normal on this compounds), no fucking fever, no setoninergic syndrome, no headache, but my muscle were frightening stretch to death. Just a crasy powerfull euphoria whis all my surrounding melt down slowly like wax whis strange colors. I thing I just had a stupid panic attac. But yes it was more powerfull euphoria that my first time on methylone (when I add 2C-D). 

I took 2 or 3 benzos to ease my muscles and all was okay (one half of nocran put me to sleep for 12 hours normaly hehehe). The comedown? Just fucking tired, I slep a lot this two last day. Feeling baseligne two days later. I think 2C-D can be extremly powerfull to kill the craving at the end of a stim session, in a FUCKING nice way.

To speak about memantine, I think I had the clear great euphoria (before I took 2C-D) and the little to no crash thanks to memantine. Want to do this mix again, without the AMT in the morning and with 10mg 2C-D instead of 20  The final word: Holly shit I crave more hehe.

EDIT: has memantine an action with seizure? Because I really felt on the comeup like I might have a fucking seizure... More fear that harm anyways, blissfull experience if I hadden think i'm going to die lol.


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## thikal

Hoo medieval I have to add this: memantine didn't give me again GBL euphoria, but she (the memantine, I don't know if I have to use "she" or "it") had take down my physical tolerance to the level I started. 3 years ago, I had to take 1,5mL to feel the effects, I climbed until 2,8mL. Right now, I just took 1,6mL anf feel like it's too much (but haven't got real euphoria). I drink 2 beer and I'm drunk too, it's funny.


----------



## MeDieViL

Well perhaps in a few days the euphoria will come, or might you be up for a 60mg experiment? Its definatly working on GBL so returning the euphoria should be possible.


----------



## thikal

MeDieViL said:


> Well perhaps in a few days the euphoria will come, or might you be up for a 60mg experiment? Its definatly working on GBL so returning the euphoria should be possible.



Yes I didn't have any side effect at 40mg so i will put my dosage to 60mg. But my suplies will end really soon I'm afraid and I have no money to order more right now. Holly shit, I have to find a job^^ I think I have to be on memantine all the summer.

Returning the euphoria should be possible yes, but if not, it's not really terrible. I think I drank more than 2L of this nasty stuff[EDIT: I mean I drank lot of GBL these last 3 years, in very truth I don't remember very well because GBL messed up my memory]. The results on the comedown with methylone and memantine are really interested by itself.


----------



## InsatiablePeace

I found chain smoking to enhance the euphoria of GBL... each and every time. GBL by itself is just sedative to me now. Cigs go hand in hand with it (similar to alcohol in fact).

Not healthy, but just an observation.


----------



## MeDieViL

thikal said:


> I think I drank more than 2L of this nasty stuff. The results on the comedown with methylone and memantine are really interested by itself.



?

Cant really tolerate cigs, so drinking some nicotine tea ive just brewed lol:
http://www.erowid.org/experiences/exp.php?ID=63157

No stims atm so well see wheter it brings some extra euphoria to g like for the above guy, i may need the maoi's in the tobacco smoke tough, wish i had some curcumin now wich would substitute for that.


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## MeDieViL

Rofl i just opened a marlboro boiled a tea out of it and the GBL euphoria is back for a big part lol


----------



## InsatiablePeace

What is the mechanism behind NMDA antagonists increasing your response to these reward inducing drugs? I don't have a clue.


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## MeDieViL

InsatiablePeace said:


> What is the mechanism behind NMDA antagonists increasing your response to these reward inducing drugs? I don't have a clue.



Receptor upregulation, the opposite mechanism behind tolerance.


----------



## MeDieViL

From this day on everyone still taking opiates, amphetamine or benzo's without nmda antagonists and then complaining of tolerance are epic failures.

Who helps the master NMDA antagonist wikipedia article where would be linked to in every fucking mention of tolerance of withdrawals regarding to some sort of addictive drug.

Dont be lazy fuckers, if you can take drugs en enjoy those benefits its time to contribute.


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## MeDieViL

bump


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## MeDieViL

Holy shit, massive g tolerance reversal with 40mg mem and 3 teaspoons of baking soda a day, 3 days in, the baking soda also stops the brainzaps and stuff, seems like too much acidic blood (ghb makes blood more acid too) makes g work bad.


----------



## thikal

MeDieViL said:


> Holy shit, massive g tolerance reversal with 40mg mem and 3 teaspoons of baking soda a day, 3 days in, the baking soda also stops the brainzaps and stuff, seems like too much acidic blood (ghb makes blood more acid too) makes g work bad.



Yes you can have acidosis with extensive use I recall, and feel real sleepy too (I don't know why). You mean that baking soda makes GHB work bad or too much acidic blood? Great tips mate, but I never want to binge again on GBL anyway (autohypnose^^)! Take some B vitamins I you use a lot of G, If you don't know that already hehe!


----------



## Torabora

so the thread is very long...Iv read the first few posts but I still have a few questions first I have only access to DXM wich is OTC.

For how long do you have to take the DXM and how much?
and if you stop taking it will the tolerance come back? for example I take it for 2 weeks then stop taking for another 2 weeks will the tolerance be back or is it removed completly? (everything without taking any drugs)

next thing wich interrests me most is that somewhere on the frist page it was mentioned that the hangover produced by amphetamine drugs can be reduced with this NMDA antagonists does anybody have more experinces with this? As Im always so wasted the next day  (other supllements like vits, fishoil, lipoic acid, 5-htb or tyrosine didnt help me either ) the hangover really stopped me from taking stimulating drugs most of the time... also longer breaks didnt reduce the hangover at all. So i really hope this will maybe help me ^^


----------



## thikal

Torabora said:


> so the thread is very long...Iv read the first few posts but I still have a few questions first I have only access to DXM wich is OTC.
> 
> For how long do you have to take the DXM and how much?
> and if you stop taking it will the tolerance come back? for example I take it for 2 weeks then stop taking for another 2 weeks will the tolerance be back or is it removed completly? (everything without taking any drugs)
> 
> next thing wich interrests me most is that somewhere on the frist page it was mentioned that the hangover produced by amphetamine drugs can be reduced with this NMDA antagonists does anybody have more experinces with this? As Im always so wasted the next day  (other supllements like vits, fishoil, lipoic acid, 5-htb or tyrosine didnt help me either ) the hangover really stopped me from taking stimulating drugs most of the time... also longer breaks didnt reduce the hangover at all. So i really hope this will maybe help me ^^



I quickly answer to you! The tolerance after DXM will stay at the same level (no receptor downregulation after upregulation), but if you take more drug tolerance will come again.

I experienced a great reduction of a methylone come down on memantine. And my tolerance to methylone drop in a niiice way! I didn't try it with amphetamine, but I think so (Other will tell you better than me, I'm not an amphetamine geek hehe). Give a try to piracetam to ease the comedown stim mate (but I think memantine is far better for this purpose, again I didn't try it so it's just speculation, but great results with methylone mephedrone MD and other cathinones, you are less E-tarded with some piracetam).

Oh and medieval, I've done all my memantine but actually enjoy a great GBL euphoria (not extreme but I'm alone so it's a important facter). I think I dosed too much before this time, and was too fucked up sleepy to notice euphoria to come back  That's funny because I have to take 1,4mL instead of 1,5mL at the begining 2 year ago. Is it possible? (euphoria isn't that good than the begingin anyway) So I will stop to hassle you with my GBL euphoria I swear hehe :D

EDIT: Oh and Torabora try curcumin for speed comedown! And read the all tread dude, you will no lose time


----------



## M Brace

thikal said:


> I quickly answer to you! The tolerance after DXM will stay at the same level (no receptor downregulation after upregulation), but if you take more drug tolerance will come again.



This wasn't the case for me.  I waited 5 weeks after stopping dxm, which I took for two weeks, before trying molly.  I definitely noticed effects from dxm while taking it, but I suspect that whatever tolerance-reversal properties it has, they aren't exactly a "reset".  Anyone else find this to be the case?


----------



## chaos_destroy

can you be sure it would have worked any better if you hadn't waited though? Have you tried it again since with less time between?


----------



## M Brace

chaos_destroy said:


> can you be sure it would have worked any better if you hadn't waited though? Have you tried it again since with less time between?



No, I can't be sure.  There are some others that have had success with this, and if I recall correctly, all who were successful with MDMA tolerance reversal used MDMA 2 weeks or sooner after using dxm. There is some safety concern with using the two substances anywhere near eachother...


----------



## chaos_destroy

The half life of dxm is quite short (1.4-3.9h according to wiki) and its metabolite dxo which is still a strong nmda antagonist only has fairly weak serotonin action. So I think two weeks is probably unnesscessary anyway to be honest. Especially since the doses used here are low to begin with. Mdma, however has a much longer half life though so the other way round would be best to wait a while.


----------



## Torabora

but DXM and DXO are also releasers and no SSRI or?

so there should be no danger of a serotonin syndrom at all


----------



## MyDoorsAreOpen

2 weeks going strong on 60mg DXM, 200mg Suntheanine, and 2 shots of black espresso to start my day. I am very impressed. I'm a third year medical student on my surgery rotation, which is far and away the most demanding thing I've ever done. I am motivated, can-do, and emotionally stable like never before. I never thought I could muster such calm and such such productivity at once. I don't take anything any asshole doctors say personally, which is something I used to have a real issue with that I couldn't will away.

I am almost certain now I will never touch amphetamine again. This is increased dopamine and serotonin tone the way my body naturally sets it, differentially. Adderall, on the other hand, was turning all the DA neurons in my body up to 11. Why tolerate the shitty comedown and side effects, when I can get enough neurostimulation to improve my life without any side effects!

I also have no taste for alcohol at all on this regimen. I know I will have it socially now and then, but I can honestly say it wouldn't kill me to never have it again.

The only downside I've noticed (especially on my job!) is a MILD memory impairment. But the tolerability of the toil is worth the trade off for sure.

I'm going to try Delsym next week and see if it's better, as a time-released prep with a longer duration, no bromine, and more conversion to DXO.


----------



## rickolasnice

DXM didn't seem to do it for me.. or maybe i just didn't try hard enough.. but a few days on methoxetamine and my phenibut addiction is gone..

People should try methoxetamine i'm not even jokin it's like a miracle cure to tolerance / addiction of other drugs..


----------



## InsatiablePeace

rickolasnice said:


> DXM didn't seem to do it for me.. or maybe i just didn't try hard enough.. but a few days on methoxetamine and my phenibut addiction is gone..
> 
> People should try methoxetamine i'm not even jokin it's like a miracle cure to tolerance / addiction of other drugs..



I find this as well but the tolerance effect doesn't last. It might make the first GBL session a lot more pleasurable but if I then start doing it on consecutive days my tolerance goes right up again. My body isn't stupid! Worst luck. Tolerance is such a bitch.

I actually really enjoy the MXE experience as well. The afterglow does make me a little bit manic though, not sure why. But totally free of OCD, depression and my focus is incredibly enhanced. I have read of people becoming tolerant to MXE as well over at DMT Nexus. They were taking it for at least a year maybe a few times per week at reasonable doses so I suppose that just the same as any drug tolerance will eventually catch up.

The magic of GBL will never be the same and I think it will eventually get to the point where it becomes even pointless taking it.

I now take 5mg of MXE every other day and I do GBL every week or so. This seems to be ok for now but it isn't anything mind blowing.


----------



## MeDieViL

rickolasnice said:


> DXM didn't seem to do it for me.. or maybe i just didn't try hard enough.. but a few days on methoxetamine and my phenibut addiction is gone..
> 
> People should try methoxetamine i'm not even jokin it's like a miracle cure to tolerance / addiction of other drugs..



Could you elaborate a bit please?

Thank you

Been using mxe myself but didnt give it enough time to conclude on its effectiveness, and then stopped using it as i didnt have any positive experience behind it and went to other stuff when i was at times i needed the tolerance prevention.


----------



## MeDieViL

InsatiablePeace said:


> I find this as well but the tolerance effect doesn't last. It might make the first GBL session a lot more pleasurable but if I then start doing it on consecutive days my tolerance goes right up again. My body isn't stupid! Worst luck. Tolerance is such a bitch.
> 
> I actually really enjoy the MXE experience as well. The afterglow does make me a little bit manic though, not sure why. But totally free of OCD, depression and my focus is incredibly enhanced. I have read of people becoming tolerant to MXE as well over at DMT Nexus. They were taking it for at least a year maybe a few times per week at reasonable doses so I suppose that just the same as any drug tolerance will eventually catch up.
> 
> The magic of GBL will never be the same and I think it will eventually get to the point where it becomes even pointless taking it.
> 
> I now take 5mg of MXE every other day and I do GBL every week or so. This seems to be ok for now but it isn't anything mind blowing.


Interesting, do you have experience with memantine or dxm for tolerance prevention?


----------



## rickolasnice

MeDieViL said:


> Could you elaborate a bit please?
> 
> Thank you
> 
> Been using mxe myself but didnt give it enough time to conclude on its effectiveness, and then stopped using it as i didnt have any positive experience behind it and went to other stuff when i was at times i needed the tolerance prevention.



I think i may have been a bit premature on the assumtion my phenibut addiction had gone..

I went a couple days here and there without it without much problems using a small dose of MXE in the morning and then a couple more in the afternoon / evenin (during phenibut use and on those days without)..

I think it's back now though (dosed phenibut friday and saturday).. Sunday was fine, yesterday was fine but this mornin i was feelin pretty ill and a bit .. the same kinda depression phenibut withdrawals bring.. But to be honest i would have been feeling alot worse alot quicker without MXE..

I've run out of MXE now and never really went long enough without phenibut to be certain.. but i'm pretty sure it's worked really well in lowering my tolerance enough to come off of phenibut without much problems..

I've taken 2 grammes of phenibut and a line of MXE this mornin btw.


----------



## alienidentikit

Hi, my first post here, so my apologies if this has been covered already.  I've read the majority of the 19 pages of this thread but not absolutely every post.  Anyway, I'm wondering about using DXM to reduce tolerance to 4-fa and 4-fma.  I'm assuming that these are similar enough to amphetamine that the effects should be similar.  Here's what I'm taking:

every day:
B vitamins
CO-eQ

most days:
aniracetam (between 300 and 700 mg per day)
choline (300 mg)

What I'm trying now:
Delsym - around 45 mg
magnesium - 250 mg
green tea extract
4-fa or 4-fma or combo: around 40-70 mg - not every day, about 2-3 times per week - mostly oral with some intranasal

I'm wondering if this will be effective.

Most importantly, I'm wondering what *NOT *to take on DXM.  I've never used it recreationally.  However I do like to occasionally take 4-mec, methylone, 2c-d, 2c-c, and methoxetamine.  

Since DXM releases serotonin (it does, right?), but since this is a very low dose (45 mg) do I still need to avoid all of the above rcs, and if so, for long do I need to avoid them for?  because tonight I figure I'll probably want to do around 10-15 mg of methoxetamine if possible.

Thanks in advance!


----------



## thikal

alienidentikit said:


> Most importantly, I'm wondering what *NOT *to take on DXM.  I've never used it recreationally.  However I do like to occasionally take 4-mec, methylone, 2c-d, 2c-c, and methoxetamine.
> 
> Since DXM releases serotonin (it does, right?), but since this is a very low dose (45 mg) do I still need to avoid all of the above rcs, and if so, for long do I need to avoid them for?  because tonight I figure I'll probably want to do around 10-15 mg of methoxetamine if possible.
> 
> Thanks in advance!



Yes I was thinking of the risks to mix MDPV and DXM, to ease the comedown, decrease the skyrocket tolerance. Did somebody tried this? I'm afraid by the increse risk of high pressure problem. 

I mixed like 100mg of DXM on an MDMA end trip without much problem (but I don't say that this mix is safe! It NOT safe!). I mixed low dose DXM (30mg) with mephedrone or methylone too and I'm not dead, but I can't say if it was benefitiall.


----------



## MeDieViL

Negative report on DXM and opiate withdrawal:
http://www.bluelight.ru/vb/showpost.php?p=9742613&postcount=26


----------



## mukaki

alienidentikit said:


> Hi, my first post here, so my apologies if this has been covered already.  I've read the majority of the 19 pages of this thread but not absolutely every post.  Anyway, I'm wondering about using DXM to reduce tolerance to 4-fa and 4-fma.  I'm assuming that these are similar enough to amphetamine that the effects should be similar.  Here's what I'm taking:
> 
> every day:
> B vitamins
> CO-eQ
> 
> most days:
> aniracetam (between 300 and 700 mg per day)
> choline (300 mg)
> 
> What I'm trying now:
> Delsym - around 45 mg
> magnesium - 250 mg
> green tea extract
> 4-fa or 4-fma or combo: around 40-70 mg - not every day, about 2-3 times per week - mostly oral with some intranasal
> 
> I'm wondering if this will be effective.
> 
> Most importantly, I'm wondering what *NOT *to take on DXM.  I've never used it recreationally.  However I do like to occasionally take 4-mec, methylone, 2c-d, 2c-c, and methoxetamine.
> 
> Since DXM releases serotonin (it does, right?), but since this is a very low dose (45 mg) do I still need to avoid all of the above rcs, and if so, for long do I need to avoid them for?  because tonight I figure I'll probably want to do around 10-15 mg of methoxetamine if possible.
> 
> Thanks in advance!



I second that. I have just started taking DXM to prevent tolerance to opiates and desoxypipradrol and I need to know which drugs to keep away from while taking DXM. Could anyone show a list?

What about MDAI for example, I would love to try it, but I obviously won't if it's unsafe


----------



## MeDieViL

Generally every drug that interacts with serotonine, tramadol, mdma, mdai, SSRI's etc, then youd be safe.

I didnt notice anything special from combining theanine with DXM, perhaps with some amp it would be better, anyone added some other drug to that combo?

I do take a bunch of other supplements tough, giving some stuff a try.


----------



## chaos_destroy

This week I've started dxm HBr 60mg twice per day which I will be doing for two weeks before trying MDMA. Last night I had K but was unable to k hole. Is there any chance that the DXM could have prevented it? I'm not taking anything else at the moment.


----------



## MeDieViL

Damned, dont know what to do when ppl arent responding on the internet, allways start rambling shit with my adhd mind.


----------



## MeDieViL

chaos_destroy said:


> This week I've started dxm HBr 60mg twice per day which I will be doing for two weeks before trying MDMA. Last night I had K but was unable to k hole. Is there any chance that the DXM could have prevented it? I'm not taking anything else at the moment.



Yes, the metabolite can stay around for a few days.


----------



## MyDoorsAreOpen

MeDieViL said:


> I didnt notice anything special from combining theanine with DXM, perhaps with some amp it would be better, anyone added some other drug to that combo?



Marijuana. Green tea or black coffee. I might experiment adding LOW doses of ondansetron, acamprosate, or tianeptine to this combo, although I'd make damn sure I was not at a greatly increased risk for serotonin syndrome.


----------



## ferinox

I recently entered my diet into a nutrition program and found out my magnesium and zinc intake was pathetic. It's been 2 weeks now since I started taking it and I feel incredible. I almost believe my anxiety and depression was all a mineral deficiency. I never noticed antidepressant effects from dextromethorphan. Is there another mechanism beyond NMDA receptor modulation that zinc and magnesium effect mental illness?

I'm also looking forward to seeing how my tolerance is effected. Something tells me it might be better than DXM.


----------



## Wizzle

MyDoorsAreOpen said:


> 2 weeks going strong on 60mg DXM, 200mg Suntheanine, and 2 shots of black espresso to start my day. I am very impressed. I'm a third year medical student on my surgery rotation, which is far and away the most demanding thing I've ever done. I am motivated, can-do, and emotionally stable like never before. I never thought I could muster such calm and such such productivity at once. I don't take anything any asshole doctors say personally, which is something I used to have a real issue with that I couldn't will away.
> 
> I am almost certain now I will never touch amphetamine again. This is increased dopamine and serotonin tone the way my body naturally sets it, differentially. Adderall, on the other hand, was turning all the DA neurons in my body up to 11. Why tolerate the shitty comedown and side effects, when I can get enough neurostimulation to improve my life without any side effects!
> 
> I also have no taste for alcohol at all on this regimen. I know I will have it socially now and then, but I can honestly say it wouldn't kill me to never have it again.
> 
> The only downside I've noticed (especially on my job!) is a MILD memory impairment. But the tolerability of the toil is worth the trade off for sure.
> 
> I'm going to try Delsym next week and see if it's better, as a time-released prep with a longer duration, no bromine, and more conversion to DXO.



I find it interesting it helps with your adhd (or are you taking it just for motivation?).. I tried some yesterday eve and this morning, and as a result I slept bad and have been feeling groggy all day.. I feel weak, but I worked out fine today. I wonder if these side effects will go away when I take it consistently, but I am reluctant to try it out, because I really feel like shit.

methylphenidate is giving me erectile dysfunction though so it seems I'm really fucked.


----------



## MeDieViL

The next substance il put some work is gonna be ibogaine, while memantine is excellent for tolerance related issues, there are still some issues left untreated namely addiction, withdrawals and mental addiction with certain substances, ibogaine may have some very interesting potential here, its more known for curing heroin addicts, but you gotta trip on it wich may limit its potenial, however less well known it can also be used in daily small doses for (intermittent) periods.

Such therapeutic possibility's have undeniably a tremendous therapeutic potential, investigating all available documentation and bringing this to a group of people that can benefit from this substance is thus warranted.


----------



## laCster

how much DXM do i need to consume to adequately antagonize my NMDA receptors enough to reduce tolerance?

60mgs? 100mgs? 200mgs?


----------



## Torabora

I think the range is more between 20-60mg for about 2 weeks


----------



## laCster

damn that might be a little hard to remain sober that long hahah.. i was hoping 3-4 days....bleh but tolerance does blow...decisions, decisions....


----------



## Saber44

Has anyone else effectively used memantine to successfully lower tolerances? I have seen anecdotal reports, but when I did it I had a bad experience. I think I increased my dosages too quickly (I worked myself up to 40mg daily within a week) and I got this pseudo-psychedelic mindset and horrible respiratory depression


----------



## Torabora

well you could try it 20mg at morning 20 in the evening for 4 days, should also have some effect, just try it out and report


----------



## Saber44

I had to work myself up to the 40mg. I started at 10mg. The half life is really long, so maybe it was accumulating. I really don't think I'll try it again. Towards the end I was getting paranoid and terrified


----------



## laCster

^^damn you get paranoid at 50mgs? mind over matter my friend....



Torabora said:


> well you could try it 20mg at morning 20 in the evening for 4 days, should also have some effect, just try it out and report



haha you stole the words right out of my mouth, except tthis time im using around 75mgs dxm once per day....


----------



## Saber44

I wasnt using DXM. I was using memantine. 40mg is a hefty dose


----------



## laCster

Saber44 said:


> I wasnt using DXM. I was using memantine. 40mg is a hefty dose



oh damn im so sorry i was on drugs when i posted tha and didnt realize, but now im on more drugs and now i relized that ur right


----------



## Saber44

laCster said:


> but now im on more drugs and now i relized that ur right



Funny how that works out


----------



## MeDieViL

Saber44 said:


> I wasnt using DXM. I was using memantine. 40mg is a hefty dose


Have been on 80mg for a while haha


----------



## thikal

Saber44 said:


> I had to work myself up to the 40mg. I started at 10mg. The half life is really long, so maybe it was accumulating. I really don't think I'll try it again. Towards the end I was getting paranoid and terrified


 
My second try With memantine wasnt the same That the First Time. Me and my girlfriend were getting paranoïde With strange effects in the heart (i think linked to stress). Opiates werent nicely potenciates l'
Like before. Maybe a low quality memantine...


----------



## MagickalKat777

I stopped using memantine because of the respiratory depression. DXM is a far safer way to go. I just wish Delsym wasn't so expensive. 15 dollars for a big bottle that will last like a week and a half! 

I still have tons of memantine lying around... I have a feeling I'm going to need both. My doc decided just to cut me off cold turkey from 20mg of Valium a day and I have about 200 1mg Kpins stored away so I think I'm going to switch to .5 twice a day and I'm also going to do 60mg of Delsym twice a day.

I just wish I could use the regular cheap cough syrup *sigh* Anyone know when the polisterex patent expires?


----------



## MeDieViL

Currently i take curcumin an NAC to see their effects on drug tolerance 1 mate confirmed nac reversed some benzo tolerance another one says curcumin and nac prevent tolerance to bupe and from my own limited experience i only saw a decline in ritalins effects when i ran out of nac witch nac reversed again curcumins modulation of creb synergizes with this.

Combined with the fact that those are the most health benefitting supplements available and having a nac supply around is good as a acute high dose can prevent psychosis when you feel one coming up.


----------



## crOOk

So, has anyone been doing this at proper doses for over a year straight?

I really wonder about the long term damage and effect on personality developement. But most of all: Can tolerance be kept at bay for years or do the NMDA-antagonists just add to the drug craze, having to add more and more throughout time? I know you can develope a massive tolerance to the behavioural effects of Ketamine and PCP which lasts forever and a day.

NMDA receptors are pretty wicked and critical for neuronal plasticity and they are all over the brain. I'm not sure if we can keep blocking them successfuly, my attempts to use any of these drugs for a long time never lasted more than 3 months.


----------



## MeDieViL

Are there any rodent student with chronic lifelon nmda inhibition?

Tolerance away forever? currently doubt it at points youd need breaks

I used to take 80mg mem for a while and later found even 10 mg still makes a major difference but its people and drug dependent

NAC is a perfect modulater for the nmda system imo restores neuroplasticity after pcp one of the million benefits

But well see how it stacks up to memantine long term definatly abolisher of bad comedown effects togheter with curcumin.
Didnt notice any crash or tolerance the last few days of using ritalin in my regime but its still to early to say shit about it.


----------



## Saber44

Holy shit. I don't know how you guys were able to use 80mg memantine.
Off of 40mg I was getting dangerous respiratory depression, and some absolutely insane depersonalization/derealization. I remember walking through my house and not recognizing it. I also remember always having the feeling when I was home alone that no one would ever come back and I would only be alone. On the last night of my memantine I wrote this insane, little gem...

"Before I begin I feel i should assure any readers that these theories/off-the-wall hypothesis were conceived in a perfectly normal, stable mindset. It is not often that I have strokes of insight that I actually feel obligated to share, but when I do I feel i should do so in it's entirety.



So, maybe I'm just crazy, but does anyone else ever entertain the idea that maybe the lives they are living aren't lives at all. Could it be, instead, a dream? Yes, It is possible. Ponder this- what if the live you lived everyday was just a subconscious dreamlike projection of yourself while your physical/corporeal body is injured/comatose/otherwise incapacitated. Assume this is true, and re-look over everything in your life. Think about how time would be perceived if your real life was actually a dream. Your childhood memories and adolescence would, in reality, have happened in the span of a few hours. You wouldn't even know the difference because of how your subconscious would cope to assure yourself it was real.



Now imagine waking up from this dream. All these experiences, perceptions, emotions, would be gone in the space of a few minutes. You would cling fast to the reality of your dream world, but in the end, it would still be just that- a vivid dream.



humor me. Take it a step farther. Assume you don't have a physical body. Assume for all intents and purposes you are deceased, and the life you are living now is just a reality created by your mind, which is no longer burdened by the task of controlling life functions. It is now free to roam at its leisure and push it's limits. Assuming this is true, other people in your world would be one of two things.

First, they could be the imprints of past people/experiences/lives you have lived or come in contact with. The people would have left enough impression whilst they were living to warrant a spot in your dream world. So when you think about it, even the most insignificant of people in our worlds (both real, or dream, however you are currently perceiving them) has some sort of priceless worth.

Secondly (and personally I entertain this idea) that the dream world we live in is the result of minds leaving physical bodies upon death. No longer bound by the restraints of physical bodies, the minds are left to wander freely and they eventually end up in one collective conscious (the "dream world"). If you have humored me thus far, do so a bit more and assume that the "dream world" is nothing more than a collective conscious- "Afterlife" if you will. Heaven and hell would have no distinction in the dream world simply because the both exist in the same reality. The choice as to what side we stray to would rest solely in the individual (which could be refutable which my earlier mention of a collective conscious). So basically, the "dream world" (IE death) would be indistinguishable from actual life except for the perception of time, which would be irrelevant assuming that the "dream world's" flow of reality was never interrupted (For example, the person waking up/coming out of a coma, etc). If you assume both are one in the same, then you know in your heart that you shape your destiny. Heaven nor Hell is predetermined, but is instead a path the users chooses to walk along.



Maybe I was just rambling. I, Myself, can see the linear progression of ideas here in what I posted, but some of you may not, which would be understandable."


----------



## crOOk

Saber44 said:


> Holy shit. I don't know how you guys were able to use 80mg memantine.
> Off of 40mg I was getting dangerous respiratory depression, and some absolutely insane depersonalization/derealization. I remember walking through my house and not recognizing it. I also remember always having the feeling when I was home alone that no one would ever come back and I would only be alone. On the last night of my memantine I wrote this insane, little gem...
> 
> "Before I begin I feel i should assure any readers that these theories/off-the-wall hypothesis were conceived in a perfectly normal, stable mindset. It is not often that I have strokes of insight that I actually feel obligated to share, but when I do I feel i should do so in it's entirety.
> 
> 
> 
> So, maybe I'm just crazy, but does anyone else ever entertain the idea that maybe the lives they are living aren't lives at all. Could it be, instead, a dream? Yes, It is possible. Ponder this- what if the live you lived everyday was just a subconscious dreamlike projection of yourself while your physical/corporeal body is injured/comatose/otherwise incapacitated. Assume this is true, and re-look over everything in your life. Think about how time would be perceived if your real life was actually a dream. Your childhood memories and adolescence would, in reality, have happened in the span of a few hours. You wouldn't even know the difference because of how your subconscious would cope to assure yourself it was real.
> 
> 
> 
> Now imagine waking up from this dream. All these experiences, perceptions, emotions, would be gone in the space of a few minutes. You would cling fast to the reality of your dream world, but in the end, it would still be just that- a vivid dream.
> 
> 
> 
> humor me. Take it a step farther. Assume you don't have a physical body. Assume for all intents and purposes you are deceased, and the life you are living now is just a reality created by your mind, which is no longer burdened by the task of controlling life functions. It is now free to roam at its leisure and push it's limits. Assuming this is true, other people in your world would be one of two things.
> 
> First, they could be the imprints of past people/experiences/lives you have lived or come in contact with. The people would have left enough impression whilst they were living to warrant a spot in your dream world. So when you think about it, even the most insignificant of people in our worlds (both real, or dream, however you are currently perceiving them) has some sort of priceless worth.
> 
> Secondly (and personally I entertain this idea) that the dream world we live in is the result of minds leaving physical bodies upon death. No longer bound by the restraints of physical bodies, the minds are left to wander freely and they eventually end up in one collective conscious (the "dream world"). If you have humored me thus far, do so a bit more and assume that the "dream world" is nothing more than a collective conscious- "Afterlife" if you will. Heaven and hell would have no distinction in the dream world simply because the both exist in the same reality. The choice as to what side we stray to would rest solely in the individual (which could be refutable which my earlier mention of a collective conscious). So basically, the "dream world" (IE death) would be indistinguishable from actual life except for the perception of time, which would be irrelevant assuming that the "dream world's" flow of reality was never interrupted (For example, the person waking up/coming out of a coma, etc). If you assume both are one in the same, then you know in your heart that you shape your destiny. Heaven nor Hell is predetermined, but is instead a path the users chooses to walk along.
> 
> 
> 
> Maybe I was just rambling. I, Myself, can see the linear progression of ideas here in what I posted, but some of you may not, which would be understandable."


Well I can definitely see your point there. You're not really treating uncommon existential issues, but I guess some of the experiences you had while seemingly separated from your body made the answers seem a lot further within reach than they really are. I personally would definitely like to believe I've integrated the dissociative experience into my religious views to a limited degree, but that becomes more apparent after use or especially during a period of frequent use.

Still it remains just that, personal issues, experiences, personal answers that count for you alone. Dissociatives tend to give me an impression of what I perceive as objective truths, so I feel like it uncovers what was previously hidden to me. It's dangerous to assume though that these realizations would come to anyone else though by your laying out your theory that really has no foundation in other peoples' reality.

There's a theory about DNA methylations generally being protective for the developement of some mental diseases and I can see how these dissociatives sometimes lift not only our memory on a cellular level as we can see with tolerance, but that maybe this same effect seems to rid us of some sort of behavioural memory that allows for free thinking, overcoming of fears and repetitive negative thought patterns, but also seems to be less beneficial to orientation in social constructs. I've seen people describe long term users of dissociatives as self centered and still can't quite make all connections as to what these substances do, especially with any long term studies on behaviour missing and everyone using these substances usually being on several other psychoactive drugs on a more or less regular basis.


----------



## MeDieViL

MyDoorsAreOpen said:


> 2 weeks going strong on 60mg DXM, 200mg Suntheanine, and 2 shots of black espresso to start my day. I am very impressed. I'm a third year medical student on my surgery rotation, which is far and away the most demanding thing I've ever done. I am motivated, can-do, and emotionally stable like never before. I never thought I could muster such calm and such such productivity at once. I don't take anything any asshole doctors say personally, which is something I used to have a real issue with that I couldn't will away.
> 
> I am almost certain now I will never touch amphetamine again. This is increased dopamine and serotonin tone the way my body naturally sets it, differentially. Adderall, on the other hand, was turning all the DA neurons in my body up to 11. Why tolerate the shitty comedown and side effects, when I can get enough neurostimulation to improve my life without any side effects!
> 
> I also have no taste for alcohol at all on this regimen. I know I will have it socially now and then, but I can honestly say it wouldn't kill me to never have it again.
> 
> The only downside I've noticed (especially on my job!) is a MILD memory impairment. But the tolerability of the toil is worth the trade off for sure.
> 
> I'm going to try Delsym next week and see if it's better, as a time-released prep with a longer duration, no bromine, and more conversion to DXO.


Hey mate,

Does this regime still work for you?

Cheers


----------



## yoyoman

I'm skeptical of the whole thing (stopping tolerance).  Tried 60mg delsym years ago daily never noticed a difference.  This was years ago and I eventually went off all stimulants/benzo's/meds for 4 years.  Those 4 years sucked i became a hermit, stopped listening to music totally (as nothing gave me pleasure).  Stopped hanging out with most people (because there was never a feeling of positive reinforcement or pleasure, only negative because of anxiety, couldn't wait to get home by myself and do passive things like watch TV)

Well its just not working out, so i'm back on stims and benzo's.  At first, 0.25 klonopin almost fucked me up like I was drunk.  Back years ago when i was on the dexedrine (60mg/day)/4mg kpin a day, it worked every day same dose.. took 4mg in the morning every day for 7 years and it always worked.

But now, for some reason, even 8mg kpin in the morning doesn't work as good and i get a lot of sedation (then i counteract that with more stims).  And, I have to add 2-4mg xanax every 4 hours or so to keep anxiety at bay.  Its strange that years later, xanax is working better than klonopin.. it was the reverse before.  Difference is i'm using d-meth oral doses until I get into this free clinic (free psych docs, free meds, even non generics).

So I bought Curcumin, NAC (n-acetyl-cysteine), l-tyrosine, DLPA (on the way in the mail), and some supposedly good quality CoQ10 100mg (doctor's best brand for both the curcumin and CoQ10 with bioperine in both, 3mg in the curcumin and 5mg in each CoQ10).

First capsule of Curcumin I took on a comedown seemed to totally get rid of the urge to redose the stimulant (d-meth) and felt a nice buzz almost.  But could be placebo because next few days tried taking 2 caps or 3 throughout the day, i should stick to just one maybe, or one in the A.M. one at night).

Now for the NAC...  I took it before the meth early in the day and it almost totally killed it.. dampened it severely (600mg NAC).  So I figure its best to take at night (when i would want to kill the effects of the meth).  Took 1200mg NAC before bed last night, the meth worked fine in the morning.  It just doesn't seem do-able to take any during the day (or maybe split the capsule and take 2-300mg?) because it basically just kills the stim.

Also, i have Pregnenolone which I read can kill just the sedating effects of benzo's without killing the anti-anxiety effects.  Nope.... it just kills the benzo including all the desired effects (anti-anxiety), not totally but I was definitely way anxious after taking the preg almost like it justs blocks benzo's.  I've read it might work differently taken sublingually but who knows.

Don't notice anything with CoQ10 but didn't expect to.  Whats a good dose, 100mg 3 times a day?  

L-tyrosine is occasionally good on a stim comedown but i notice it only works (gives me a nice feeling and less of the bad comedown feelings) if I use it sparingly, not every day.  Like 1-2g empty stomach.  BTW, had a bottle of N-acetyl-L-tyrosine and I think it sucks it does not seem to absorb better or do anything at all no matter how much I took so its probably a sales gimmick.. 

My sister has PKU (inability of an enzyme to convert phenylalanine into tyrosine properly, leading to dangerously high "phe" levels in the brain) and i could be a carrier (50% chance).  I've read somewhere even carriers can *possibly* have very very slight PKU.  So i'll see what DLPA does (if anything noticeable at all).
------
Oh, one more thing, the reason I quit meds was I went totally psychotic (60mg or more dex a day) but I just wasn't sleeping right.  Lately been using seroquel which knocks me out and seems to KILL all stim effects (i get hungry etc and seem to feel the benzo's a lot more if i walk around).  I found trazodone to also work well.  Hydroxyzine is wonderful stuff too for sleep but its not as good if there's still enough stimulants in your body at night.  But as long as i get a solid 6-7-8 hours of good sleep, i never notice a hint of psychosis type stuff ever.


I am curious about memantine but I am just gonna bet that it'll kill the stims effects if anything.  Seems like its always a catch-22.  All these benzo's in my system halt my sex drive which sucks (only way to get horny is to do a large dose of a stimulant).  I can chat with the hottest girls on these drugs and have actual conversations that give me pleasure, but have less of a sex drive  .  I've tried a handful of SSRI's but they make me feel SO SHITTY and twice as anxious, that I can't stand them for more than 2 days to allow them to "kick in" after weeks.  I hear close friends of mine saying celexa (one of the worst for me) and prozac are helping their anxiety a lot.. makes me almost want to try again and hope benzo's chill me out enough for it to actually kick in.


----------



## Dunno

Does this work for Oxycontin? & is it the same dose & safe to take with oxycontin?.


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## Dunno

Anyone ?


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## sekio

First off, don't bump your post, and second - this is a thread of anecdotal reports, how about you read it and judge for yourself? I un-approved the other two posts you made in a similar thread. Bluelight is not a real time chat; it's a public forum that sometimes moves very slowly.

There are no "miracle cures" for tolerance, and especially not when you get opiate abuse involved.


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## Dunno

Psycho lol...I dont have time to read it all & i'm not abusing opiates. I just want to know peoples opinions?


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## sekio

Don't expect people to hold your hand - there's 20 pages of experiences you are sitting on that you "don't have time" to read.


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## Dunno

true....read few reports.lotta conflicting


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## MyDoorsAreOpen

I'm making a retrospective "5 months on 60mg of DXM" post soon in Trip Reports. Stay tuned.


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## Dunno

Cool let us know when it's done. In combination with opiates or benzo's?


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## MyDoorsAreOpen

Neither, actually. It was originally for amphetamine tolerance, then for fixing my downregulated catecholamine receptors after long-term amphetamine use. Now it's just for maintaining a positive and hard-working mood. I'll never have an opiate or benzo habit, insh'Allah.

NMDARAs have definitely lowered my tolerance to alcohol, caffeine, and pseudoephedrine, though, such that one beer or one 12oz coffee gives me all the effects I could possibly want.


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## MeDieViL

Ive been off memantine for a while now, i beleive there are several other more interesting compounds out there but working on putting info togheter and testing stuff out.


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## MagickalKat777

Does anyone have any experience with same day dosage? I'm going through W/D from alcohol right now and I'm wondering if 20mg of Delsym would help or make things even worse...


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## /navarone/

*Neramexane*




http://en.wikipedia.org/wiki/Neramexane

Did anyone here get their hands on some of this? I've read that it's about to be put on the market in some countries.
Seem pretty kEwL..


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## MeDieViL

Bump, this thread has been dying out.

Surely more ppl have tolerance issues and want to give this stuff a try


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## chaos_destroy

I have been meaning to post my unsuccessful DXM trail for MDMA. I used 60mg of DXM HBr twice daily for 14 days followed by a 3 day break as well as around 400mg magnesium glyinate. I then consumed 150mg of high quality MDMA followed by 75mg one hour later. I noticed no increased activity at all. no return of effects of any kind. To be fair it wasn't the best set and setting considering I had just had a fight with my GF but I still expected something more than what I got. I have tried it again since (without the DXM though) a few weeks later with the same stuff also with no success. 

Do you think that the yoyoing plasma levels caused by using normal DXM rather than the polisterix could have reduced its effectiveness? They don't sell delsym down here so would perhaps using 30mg four times a day work better?

Also as I mentioned in an earlier post during this time I could not K-hole which I first contributed to the DXM however since stopping the DXM but continuing with the magnesium I noticed I still had trouble k-holing. Since stopping the magnesium k seems to work again.

On a side note during the DXM trial I noticed pretty much complete elimination of social anxiety as well as hangovers and anxiety from alcohol and anxiety from caffeine. This was maintained to some extent once stopping the DXM but nowhere near as much as when taking the DXM.


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## MagickalKat777

Magnesium will reduce plasma levels of MDMA. I have noticed this as well as my friends have noticed the same thing.

As for the tolerance - MDMA is a drug that works off of a certain amount of serotonin and dopamine being available - if they aren't there, no amount of DXM will get you where you want to go. On top of that, the reduced tolerance takes longer than 2 weeks with DXM. Memantine is a much more suitable drug, especially since you can take it WITH MDMA without any serious side effects which I assume is why you took a 3 day break from the DXM before taking the MDMA in the first place.

If you really want MDMA potentiation, I would drop the DXM and the magnesium and get either piracetam or aniracetam instead. They have a proven track record of increasing the effectiveness of MDMA and other amphetamines, base phenethylamines, tryptamines, beta-carbolines, ergolines, and many other drugs without any real negative side effects. Once again though, you have to have them in your blood when you take the drug you are trying to potentiate.


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## chaos_destroy

Interesting about magnesium reducing MDMA plasma levels. Are there any publish studies on that or just anecdotal reports? I though magnesium was a fairly common thing to take with MDMA. I didn't use magnesium on the second try though maybe by then it had been to long since the DXM. I did use NAC, alpha lipoic acid, berroca (multi B) and vitamin C as well but again only on the first try.

Other than mild social anxiety I have no signs of low dopamine or serotonin so I doubt that is what is causing this. Back when MDMA did work on me, my anxiety was much worse if anything.

I've read of others successful attempts with delsym for only 2 weeks. Though I was thinking of trying to get delsym and trying it for a month. Maybe even not take a break just not take it that night as the low levels used here probably wouldn't pose much of a threat really. 

I've tried long breaks, piracetam, aniracetam, SJW, 5-HTP, and now DXM so far with no increase distinguishable from placebo. I'd like to try memantine but Aussie customs are pretty good at their job. Other than making caffeine unbearable and enabling me to remember a heavy night on the piss I didn't notice much affect of the racetams on drugs.


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## thikal

Maybe this quote I posted in the MXE megathread will be interesting here:



> I've notice something strange too: MXE seems to bring my GBL euphoria back. I tried memantine and DXM to lower my tolerance to GBL (I was taking 2,8mL at the end, started at 1,5mL). With a memantine cure of 4/5 weeks I was again at 1,5mL, the physical tolerance was lowerded, but euphoria and aphrodisiacs effets weren't there. I've to think at this more and wait a bit more time to say a conclusion, but it's seems really interested!


----------



## M Brace

chaos_destroy said:


> I have been meaning to post my unsuccessful DXM trail for MDMA. I used 60mg of DXM HBr twice daily for 14 days followed by a 3 day break as well as around 400mg magnesium glyinate. I then consumed 150mg of high quality MDMA followed by 75mg one hour later. I noticed no increased activity at all. no return of effects of any kind. To be fair it wasn't the best set and setting considering I had just had a fight with my GF but I still expected something more than what I got. I have tried it again since (without the DXM though) a few weeks later with the same stuff also with no success.



This was my experience with DXM (robotussin) as well.  No noticeable increase in MDMA's effects, if anything -- less of an effect.  I took for one week, and waited 4 weeks, if I recall correctly.  




chaos_destroy said:


> On a side note during the DXM trial I noticed pretty much complete elimination of social anxiety as well as hangovers and anxiety from alcohol and anxiety from caffeine. This was maintained to some extent once stopping the DXM but nowhere near as much as when taking the DXM.



Also, I had amazing relief from social anxiety.  I felt great confidence in social situations.  It might be worth taking for that reason alone!  

I'm interested in trying memantine, but concerned about combining it with mdma.  I recall reading that some people had difficult cardiovascular side effects with the two.  

I did have a recent unplanned roll that went pretty damn well.  I had snorted a little K and about an hour and a half into that someone offered me some molly.  Sober, I would have said nooooothankyou.  But, with shields down, I ate the little capsule.  An hour or so later, I felt lots of love, and a little knocked on my ass until the K wore off. And I was able to control my desire to redose.  All in all a satisfactory experience. 

I'd like to experiment with a sub-threshold or near threshold dose of K to potentiate mdma.


----------



## MagickalKat777

M Brace - nice name btw - I have used memantine and MDMA and if anything, the MDMA knocked out the memantine's hold on my lungs. Being a stimulant that shouldn't be surprising. The issue I had with memantine is I noticed marked respiratory depression once I hit the recommended 40mg marker. I did, however, test out MDMA on memantine and I noticed that I could breathe again. Well store-bought ephedrine did the same thing back when it was easy to get (ah, the primatene days).

Anyway, DXM ***HBr*** is *NOT* the form you need for long term NMDA antagonism. DXM itself is not what is needed - we want the DXO. DXO is a semi-potent NMDA antagonist but it has a short half life. When you "get fucked up" on DXM, you use the HBr version which as soon as it hits the liver it is rapidly metabolized by CYP2D6 to DXO which is then processed by the body and we have a DXM trip. If I remember correctly, DXM by itself is pretty much a SRI (serotonin reuptake inhibitor) which is why certain people low in CYP2D6 liver enzymes have extremely long trips and sometimes dangerous reactions to high dose DXM. This is also the reason that DXM, unlike the traditional NMDA antagonists like ketamine, PCP, methoxetamine, alcohol (yes its an NMDA antagonist among other things), etc - in low doses it feels quite serotonergic. Nice and fluffy. I don't know any dose of K that makes you feel like you're on a mild to moderate roll. DXM is active on its own and its activity on serotonin is much more responsible for the serotonin syndrome fear when combined with MDMA or other serotonin releasers than DXO is.

Anyway, that was really scattered... DXM ***POLISTEREX*** is what you need. The conversion factor between HBr and Polisterex is entirely different. Polisterex (ONLY available as Delsym, no generic form) is an edible plastic... its like an enteric-coated DXM molecule... the stomach slowly eats away at the plastic and sends the DXM down for absorption (and subsequent conversion) to DXO over the course of 8-12 hours (depends on metabolism like all things). This is where the magic comes in. NMDA *stays* antagonized and gives the brain a chance to recover at GABA (and probably dopamine receptors).

Now as far as MDMA goes - seriously dude, once you've lost the magic, you've lost the magic. Piracetam has been shown to bring it back but it also increases the potency of MDMA and while in my experience it lessened cardiac effects of MDMA, I have heard the opposite as well.

Now referring to DXM's ability to ameliorate anxiety, this is because N-Methyl-D-aspartate (NMDA) is the "excited" part of the brain. It is what makes us react to certain situations and has been shown to trigger adrenaline release. When you have sufficiently beaten down NMDA you have done two things - one, eliminated most of the brain's causes of anxiety (AMPA plays a role in anxiety as well but the only well-known AMPA inhibitor I know of is Topamax. In my circle we call it Dope-a-max, or Stupidmax because it dulls you down THAT much) and two increased the brain's "calming" side - gamma-aminobutyric acid (GABA). The balance of these two is something the brain always tries to achieve. When you consume too much glutamate or alcohol/benzos you can alter that balance drastically. 

Basically all this method seeks to do is allow the brain to compensate for the loss of NMDA (due to inhibition) by producing more GABA. The flipside of the coin would result in seizures and death. If you antagonize GABA, the brain flips on the NMDA switch and we seize and eventually die from cell overactivity.

This is pretty much a crude way of tricking the brain into thinking it needs to produce more GABA.

EDIT: Shit, I forgot to add... I just started Delsym for Klonopin taper... First night... 16-17mL... I have had a few beers and one thing I always noticed with beer was my heart rate. Plagued me even when falling asleep. Now I know that taking trazodone with DXM can cause permanent liver damage so its either Remeron (which has an extremely sketchy pharmacological profile IMO) or just go to sleep on my own... well I walked to the bathroom because Delsym has an annoying "flush" effect on my bowel system the first few days... checked my pulse... normally would be about 120 or so with alcohol... yet it was around 70-80... that's my normal resting (smoker) - its obviously already doing its job... I feel pretty relaxed although my body is quite angry with me... my CNS is quite calm. Its the southern region that wants to punch me in the face. I think that the antagonism starts pretty fast... That's not to say I'm going to skip my Klonopin tomorrow... I might wait 6 hours or so but take my Delsym as normal... I'll report back on what I decide to do and see what happens. I know that normally missing it more than an hour usually puts me in rebound mode but 20mL might just do the trick.


----------



## crOOk

MagickalKat777 said:


> alcohol (yes its an NMDA antagonist among other things),


i recently read a study showing that the nmda antagonism of ethanol is of extremely short duration (few minutes) after which an increased opening probability of the nmda receptor channels is observed.


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## MagickalKat777

crOOk said:


> i recently read a study showing that the nmda antagonism of ethanol is of extremely short duration (few minutes) after which an increased opening probability of the nmda receptor channels is observed.



Absolutely true. This is one of the hypothesized things that contributes to alcoholism. If I remember correctly, a shot of whiskey has NMDA antagonism that lasts about 30 minutes while a shot of tequila lasts about 15. That is, of course, AFTER it has been absorbed - varies obviously.

The theory is that most alcoholics become addicted to the "calm" - they chase after it and as their BAC rises, different parts of the brain are affected until they turn into a mess. Been there, done that. Got the probation to prove it! =/


----------



## MagickalKat777

Okay... NMDA antagonism SUCKS when you are first starting it and trying to get drunk! I've drank 18 beers and I don't feel much more than the actual DXM... >_< Guess that means its already working though.

Oh, my pulse is 62... normal resting is about 80-90 usually. Something is going on for sure. Sucks I can't take trazodone though because I haven't slept yet and would like to!

Well... alcohol buzz is there... but totally different... I didn't feel it til just now but its like DXM lite... I'm freezing like I would if I was tripping DXM but my coordination is shot and I am getting double vision. I took my dose at 12 and its 9 now... maybe there is an amphetamine-like corolation with DXM and drinking where you suddenly come down and get drunk?


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## MagickalKat777

Okay so long story short - when I hit noon, I was fucking balls to the wall smashed.

I forgot to take my scheduled Klonopin dose... I'm up 4 1/2 hours later with rebound anxiety... took the pill with 15ishmL of Delsym and I know it takes exactly 1 hr 20-25 minutes for Klonopin to hit me. Delsym hit first. I went from full blown panic mode to zero in no time flat. (20 minutes or so after taking the large Delsym dose).

Has anyone ever explored low dose ER DXM as a possible anti-anxiety agent much like ketamine does for depression?


----------



## PitheGreek

I really need some ideas what is going on with my memantine use... After I followed the whole thread, I got really interested to try memantine for my NDRI tolerance (methylphenidate, ethylphenidate, buphedrone). The first day after I stopped buphedrone and started memantine (10mg) I felt really clear headed, being in a good mood the whole day. The same happened the second day. The third day I had to up to 20mg for the same positive feeling (dopamine agonism?). After a week in 20mg I thought to try a little buphedrone, being courious to see if memantine made any difference for my tolerance. Here is what happened that I find puzzling.

For maybe a good half hour after consumption, I got a very unusual euphoric feeling. Not quite what I am used with buphedrone, seemed more euphoric but not in a "well rounded" way, something was missing from the first few times I got a good stimulant effect from buphedrone (I mainly use it as a functional stimulant to get stuff done). After that the whole thing went quite bad really dysphoric, stressed and almost sick. The exact same thing happened with 50mg ethylphenidate the following day. Memantine is good (but subtle) on its own, but its getting dysphoric with the stimulants I mentioned, any ideas what is going on? Is it too soon to add the stimulants with memantine?


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## Torabora

M Brace said:


> This was my experience with DXM (robotussin) as well.  No noticeable increase in MDMA's effects, if anything -- less of an effect.  I took for one week, and waited 4 weeks, if I recall correctly.
> Also, I had amazing relief from social anxiety.  I felt great confidence in social situations.  It might be worth taking for that reason alone!



well dont forget that DXM is a weak SSRI alone, so taking it over week is the same like taking a low dose SSRI, maybe a other SSRI could also help you with you problems!

I could also imagine that the tolerance lowering with MDMA doenst work because of this SSRI property as the drug on the one hand maybe reduces tolerance but on the other also stimulates the serotonine receptor and so the effect is zero in the end (but it should work on dopamine and norephenidirne-->amphetamine and coffein which was reported quite often now)


----------



## mesmer

I've been on relatively low does of kpin (.5/day) for about 4 or 5 years now for sleep/anxiety issues. I wish I had never got on it, but c'est la vie. Within the past month I seem to have found myself in some sort of "tolerance withdrawal" hell of intermittent panic, tinnitus, burning skin, chills and sweats, etc. I'd like to avoid playing the chase the tolerance with upping the dose game, in fact I want to taper off. Interested in these reports of memantine and DXM being useful for up-regulating GABA receptors. Could possibly get rid of this tolerance withdrawal or allow an easier taper??

My only concern is that I am also on Zoloft for 5+ years for depression (am now tapering to Vibryyd, essentially an SSRI with a little extra 5HT1A agonism - may explain the side effects some people are getting on high doses of "trippiness")

I don't think a low dose of DXM is particularly worrisome for serotonin syndrome, others may disagree, would adding in, say a normal therapeutic dose of DXM and moving upwards to see if it reverses any of these symptoms (tinnitus especially) be an alright course of action. Memantine sounds more promising, but would have to scope a source.


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## Torabora

well some doctors would maybe even give you a prescription if you argue well for what you want it (but depends very much on the person).

For DXM and SSRI: I also think that it is not too risky to start with 20mg, a serotonin syndrom does not start with nearly dying, you will get headache and other symptoms way before it really gets bad. Also DXM has a relatively short half life (compared to "real" SSRI's) so you could easily stop taking it when you get the first possible symptoms.


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## mesmer

Unfortunately, while I have a pdoc that treates me like an adult and we have interesting conversations, I don't think she will support off label use of a drug like memantine for benzo taper. She still thinks that I should be able to taper in a couple weeks tops since .5 is such a low dose, despite all the reams of evidence to the contrary. I will see how DXM works, at least for taking away these new tolerance withdrawal symptoms and write up a report somewhere.


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## negrogesic

mesmer said:


> I've been on relatively low does of kpin (.5/day) for about 4 or 5 years now for sleep/anxiety issues. I wish I had never got on it, but c'est la vie. Within the past month I seem to have found myself in some sort of "tolerance withdrawal" hell of intermittent panic, tinnitus, burning skin, chills and sweats, etc. I'd like to avoid playing the chase the tolerance with upping the dose game, in fact I want to taper off. Interested in these reports of memantine and DXM being useful for up-regulating GABA receptors. Could possibly get rid of this tolerance withdrawal or allow an easier taper??
> 
> My only concern is that I am also on Zoloft for 5+ years for depression (am now tapering to Vibryyd, essentially an SSRI with a little extra 5HT1A agonism - may explain the side effects some people are getting on high doses of "trippiness")
> 
> I don't think a low dose of DXM is particularly worrisome for serotonin syndrome, others may disagree, would adding in, say a normal therapeutic dose of DXM and moving upwards to see if it reverses any of these symptoms (tinnitus especially) be an alright course of action. Memantine sounds more promising, but would have to scope a source.



The 'promise' seems limited, and that is irrespective of the zoloft issue. A better choice maybe high dose gabapentin.

Your situation is somewhat reminiscent of the case report on page 75 (of the PDF):

Topiramate use in alprazolam addiction


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## mesmer

yes, Topamax has it's own problems though. Not the least of which that it makes you as dumb as a rock. I will try a week of DXM and see if any symptoms disappear.


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## negrogesic

Certainly; it was just an example. I recommend high doses of gabapentin to facilitate the final dose reductions (particularly, X mg - 0mg). There is no easy fix however. Ultimately, the only way out of the BZD conundrum is to reach 0mg. Your physician should help you determine the dose, but at some point you are better off jumping to zero than playing an endless dose reduction game. High doses of gabapentin or potentially pregabalin may reduce the risk of potential seizure (rare) from total discontinuation, and can reduce some of the somatic symptoms of the acute withdrawal. In theory, all quitting is 'cold-turkey', but again, safety is a concern with BZD.  

Take care with the DXM use, as it may be contraindicated in your case, and its efficacy for your intended purpose is at best anecdotal. When it comes to BZD withdrawal, prominent symptoms are unlikely to disappear as a result of any form of pharmacological intervention.


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## MeDieViL

Bump


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## atrollappears

I've mentioned Huperzine A in a few other threads: it's possibly a very useful NMDA antagonist as it is available cheap as a supplement, does not produce dissociative effects, and is not anticholinergic (the opposite, it inhibits AChE). I haven't experimented with it for the purpose of tolerance yet; however, I just spent 9 days off of amph while taking huperzine for most of those days, so I will try taking my usual dose and see how that works out. There are confounding variables though, since I have been taking other supplements, including curcumin.

Edit: Took my usual amph dose (20 mg adderall IR) a few minutes ago, with usual accompanying supplements & antacid. I haven't yet taken my evening dose of huperzine, and my morning dose should be cleared out by now, so this should show the cumulative effect of huperzine on drug tolerance (although as I mentioned a change could be due to other factors), rather than acute. Later on I'll add in my evening dose to see how that effects it. As far as positive mood effects go, it doesn't look promising with huperzine's acetylcholinesterase inhibition: http://www.sciencedirect.com/science/article/pii/S0091305707003723

T+0:45: Feeling the effect more strongly than usual. I have an urge to talk to people and a willingness to go out of my way to be friendly which I haven't felt in a long time on amph.

T+2:00: Took a dose of huperzine at T+1:00, doesn't seem to have potentiated it, but it did seem to smooth out some of the amph tunnel-vision/introversion which I appreciate. Probably not a hugely effective potentiator, but it's hart to tell since the euphoriant effects were already starting to wear off when I took it.


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## m060mm

Context: 
First attempt at using MXE for it's antidepressant qualities. Ideally it'll also lower my minimal amphetamine tolerance. You can probably tell from my adderall/4-FA dosages that my tolerance isn't high. These dosages have consistently worked well for me. They're not working today.

About 30 minutes after taking the magnesium I felt really tired. Hence the stimulant use. Suddenly, inexplicably tired/weak (slept well last night; I've eaten plenty).

Questions:
1. Why have my muscles felt weak since taking the magnesium? (This hasn't happened in the past; the only new factor is MXE.)
2. Is MXE blocking the stimulants?
3. Does MXE's DRI qualities bar it from reducing/preventing tolerance the way DXM/ketamine does? (Obviously anecdotal evidence is welcome.)

T 0h 5mg MXE insufflated
1.5h 5mg MXE insufflated
3.0   h 400mg magnesium malate
3.5h 15mg adderall, 1000mg calcium carbonate
4.0   h 30mg 4-FA, 500mg calcium carbonate (this time because the chewy ones taste good)
5.5h Bluelight post (hah, for relative timeline)

Amphetamines primarily work as DRI's in this dosage range, correct? One explanation could be that MXE has a stronger affinity as a DRI and is blocking the amphetamines.

Google suggests myasthenia gravis can be triggered by parenteral magnesium. This isn't my area of expertise.


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## atrollappears

Amphetamines are primarily DRIs only in very low doses, I think lower than 15 mg actually, unless you have a good tolerance. Still, DRIs block the action of amphetamine to some extent (whether or not this outweighs the additive stimulant properties) because amphetamine must be taken up through the dopamine transporter to work. However it's my impression that that much MXE should not significantly block the action of amph/4-FA. You're probably accruing tolerance. NMDA antagonists don't work for everyone, anecdotally.


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## Saber44

Following my respiratory depression scare from the memantine, I had lingering breathing issues for a few months. Just a heads up0 purely anecdotal of course


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## delphinen

It had to be a very strong dose of Memantine.. I can assure you 10mg puts me a little alert, and it works incredible for uppers (any kind) tolerance.

But once I did like.. I don't know, +100mg Memantine and I felt some breathing and cardiac issues too. Also if I would concentrate really hard in silent with my eyes closed I swear I would remember the feeling of a K low dose. But it was very subtle and mild. Never again.


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## Saber44

Yeah I was doing the regime and I worked my dosage up too fast I think. I knew the half-life was extremely long but I underestimated it.


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## Material541

A couple of months ago I was sick with a minor cold and started taking cough syrup (~30mg DXM HBr) twice a day. This lasted about 4-5 days. My DOC is tramadol, and I was not using it during this period. I usually go one week on the tram followed by two weeks off with it...and have been holding to this pattern for a few months now. After my minor sickness was over and I returned to tramadol use, I discovered my tolerance had been noticeably reduced. I needed about 30% less tramadol to get to where I normally get on my first dose after 2 weeks of abstinence. 

After some research, I found this thread and read through it. I wanted to test it out, so I have been taking ~120mg of DXM polistirex daily for almost a week now. I hope this is a good amount to start with. I will continue to do so until I start my tramadol cycle again, perhaps a week from today. I have been keeping a close eye on my use habits, particularly in relation to tolerance. I will report back to this thread soon with an update on my findings.


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## Material541

I finally got around to this. Took my normal dose of tramadol recently. As I thought, opioid activity (itching, propensity to nod) was noticeably heightened. The stimulant effects were also affected, but not nearly as much. I wonder why. I would say that the effects were slightly higher than the 30% I experienced upon without intentionally attempting to reduce tolerance. I cannot say that this lasted too long however, as I found myself increasing the dosage to get to the same point as I did on the first day of tramadol use. 

This is certainly something I will continue to experiment with -- will take a longer break from tramadol (at least 4 weeks) and half the DXM (to 60mg a day) to see how that affects it.


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## thikal

Just before my post, I'm really tolerant to GHB/GBL, and tried memantine to kill tolerance. It worked a lot (2,8mL to 1,5mL in a few weeks with 20 or 40mg memantine a day), I already report that before on the topic, but memantine wasn't able to bring back euphoria. I understood that memantine is perfect to cure the GABA aspect of GHB/GBL tolerance, but keep intact the GHB receptor downregulation. 

I read something really interesting in wikipedia (maybe you already know this but anyways!  ). 



> The benzamide neuroleptics (including sulpiride, amisulpride, and sultopride) have been shown to activate the endogenous gamma-hydroxybutyrate receptor in vivo at therapeutic concentrations.[1] Sulpiride was found in one study in rats to upregulate GHB receptors.[2] GHB has neuroleptic properties and it is believed binding to this receptor may contribute to the effects of these neuroleptics.



http://www.ncbi.nlm.nih.gov/pubmed/9652377

And more especially this study:


> Sulpiride, but not haloperidol, up-regulates gamma-hydroxybutyrate receptors in vivo and in cultured cells.
> Five days of gamma-hydroxybutyrate (GHB) administration (3 x 500 mg kg(-1) day(-1) i.p.) to rats resulted in a significant decrease in the density of GHB receptors measured in the whole rat brain without modification of their corresponding affinity. Similar administration of (-)-sulpiride (2 X 100 mg kg(-1) day(-1) i.p. for 5 days) induces an up-regulation of GHB receptors without change in their dissociation constants (Kd). Haloperidol (2 X 2 mg day(-1) i.p. for 5 days) showed no effect. Administered chronically via osmotic minipumps directly into the lateral ventricles, (-)-sulpiride (60 microg day(-1) for 7 days) and GHB (600 microg day(-1) for 7 days) up-regulated and down-regulated rat brain GHB receptors, respectively. Finally, in a mouse hybridoma cell line (NCB-20 cells) expressing GHB receptors, the treatment of these cells with 1 mM GHB, 100 microM (-)-sulpiride or 1 mM GABA decreases, increases and induces no change, respectively, in the density of GHB receptors after 3 days of treatments. These results indicate that chronic GHB treatment modifies the expression of its receptor and that sulpiride also induces plastic changes in GHB receptors perhaps via antagonistic properties.



Do you know more about this? Did somebody tried with some success to renew his GHB receptors with sulpiride or amisulpride/sultopride? My girlfriend is on valium, risperdal and memantine for her GBL dependance. Maybe sulpiride is far better in her case than risperdal? Thanks a lot for any input!


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## /navarone/

Campral (acamprosate) could also be a relatively available or rather easy to get prescribed NMDA antagonist and GABAa agonist. It has been approved in the US as well since 2004, however it is not very cheap.

http://en.wikipedia.org/wiki/Acamprosate


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## MeDieViL

Risperdal for G dependency wtf? Ap's shouldnt ever be used for anything else then shizophrenia due to their severe toxiticy problems and long term issues; a short course of amisulpiride wont be a problem tough.


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## alkap555

> Do you know more about this? Did somebody tried with some success to renew his GHB receptors with sulpiride or amisulpride/sultopride? My girlfriend is on valium, risperdal and memantine for her GBL dependance. Maybe sulpiride is far better in her case than risperdal?



Why would you want to up-regulate the excitatory GHB receptor if you are going to be withdrawing from GHB/GBL. Me thinks this would greatly exacerbate the delirium/psychosis associated with GHB abstinence syndrome, as well as likely increasing the excitotoxicity. 

Personally I wouldn't mess with neuroleptics just so I could "get the euphoria back." If its not doing much in the way of fun, then maybe its best to get off the stuff with a Baclofen/Phenibut taper.


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## Epsilon Alpha

/navarone/ said:


> Campral (acamprosate) could also be a relatively available or rather easy to get prescribed NMDA antagonist and GABAa agonist. It has been approved in the US as well since 2004, however it is not very cheap.
> 
> http://en.wikipedia.org/wiki/Acamprosate



*cough* just buy homotaurine *cough*
Pretty sure the whole deal with acamprosate's N-acetyl group was to make it patentable seeing as homotaurine is found in several seaweeds.


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## thikal

MeDieViL said:


> Risperdal for G dependency wtf? Ap's shouldnt ever be used for anything else then shizophrenia due to their severe toxiticy problems and long term issues; a short course of amisulpiride wont be a problem tough.



Yes I was a little puzzled when she came back with a script of this shit. She have sleep problems, and it was a good choice according to the doctor, because it's non addictive. (?!?) She take valium (prescribed by the doctor) too and memantine, and funnily she said to me that increase memantine from 10mg to 20mg decrease her lever of anxiety and depression. Maybe reach 30 or 40mg memantine a day could be even more beneficial? I was reluctant to let her mix memantine (the doctor don't know that) with her other medications, but after a few weeks it seems that memantine is far better than 3 valium a day (she took one valium a day max!), she is already more alive than a few months ago and want to quit risperdal.



> Why would you want to up-regulate the excitatory GHB receptor if you are going to be withdrawing from GHB/GBL. Me thinks this would greatly exacerbate the delirium/psychosis associated with GHB abstinence syndrome, as well as likely increasing the excitotoxicity.



I'm not addicted physically to GHB now, but don't feel euphoria anymore. In fact, i feel really depressed and exhausted after a single dose of GBL now so I try to don't take that anymore. It makes me think that my GHB/GABA system is still weak, and tried to find something do balance it a little bit, if possible but I don't have great expectations hehe


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## MeDieViL

Anecdote of a personal friend says that DXM allowed GBL to stay working well; its possible DXM is more effective for GBL perhaps give that a trial run and eventually amisulpiride. Id be curious for your results.
I cant try it as G gives me abscence seizures at every dose.

now i think about it...

When tolerant to gbl it feels more sedating and far less euphoric this would indicate the problem is in the GHB receptor; G does indeed downregulate the ghb receptor wich amisulpiride upregulates again altough im sure GABAB downregulates as well.

Ibogaine has been reported on drugsanddogsforum to reverse G tolerance too. 

Anecdotally its know the racetams potentiate several drugs (personally i experience massive mpa potentiation of mpa) however the racetams likely accelerate the formation of new tolerance (eg look up ethanol aniracetam) however one anecdote suggests that the combo of a racetam and a nmda antagonist offers the best of both worlds.


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## sekio

In response to some of your (stimulant induced?) musings, (please for the love of your_deity_here use the edit button) -



> DXM allowed GBL to stay working wel


From what I have heard, GHB/GBL is pretty reliable in terms of producing effects, pleasurable or otherwise, unless dosed very frequently.(seeing as it's an endogenous n/t and all). 1-3x a day is probably nothing to worry about. I guess it varies between people.



> G gives me abscence seizures at every dose.


*Every* dose? And is it an absence seizure you're experiencing, or simply somnolence/"microsleeps"? GHB is a known & powerful inducer of sleep in many individuals.
From what I have heard, the stimulating f/x of GHB are more prevalent at lower doses (less than the typical 2-3g) due to the relatively low affinity for GABAb vs GHBr. Or you may even try combining it with e.g. caffeine or another, (even amphetamine-type) stimulant as long as you don't overdo it.

Racetams do indeed potentiate stimulants, I believe that it has something to do with increased activity at certain metabotropic glutamate receptors (of which racetams likely modulate & amphetamine derivatives interact with). Do note that NMDA/AMPA are ionotropic & not metabotropic so this would still be a 2nd order effect.

On the topic of ibogaine & DXM, they are both pretty broad-spectrum drugs and are much more than a "pure" NMDA antagonist. I know Ibogaine at least is a SNDRI (S>D>N in terms of potency) plus opioid agonist (mu and kappa) and also interacts with 5-HT receptors. It's not very potent but people take it in multi gram boluses so I would expect a real fireworks show. DXM is "only" a SNRI (N>S) but has all this funky rate-order mechanics shit with the conversion to DXO (which is more potent as a NMDArA, and from what I can tell seems more like a version of ketamine with activity at SERT). In addition both drugs are calcium channel/nicotinic blockers (as is ketamine/MXE/memantine). There is also sigma-1 and 2 agonism to consider as well... truly rhese drugs that are thought of as NMDA antagonists may be working through other modes of action.

I wonder how much of it is all psychological, though, from people simply becoming 'entrained' to drug use... like riding the same roller coaster every day, if you will. You can ride that coaster every day until you no longer find pleasure in it, and when that point is reached you can definitely come back after months or years of being in a different mind state & recapture that thrill. Of course it will never be quite as exciting as the first time because some of the novelty has gone, but it likely won't be 'boring' as it were if you were riding it daily for 3 weeks. Continuing to ride the coaster over and over when you don't like the experience should be reserved for roller-coaster test pilots & sadomasochists. I'm not denying that some drugs develop a physical tolerance, but in some cases I bet it's just a case of your 'escape of choice' becomign boring.

Re: risperidone for ... well, anything but major delerium & schizophrenia - wtf? I do not understand why this industrial strength antidopaminergic is prescribed as frequently as it is. From whatI have read it seemms incredibly effective at makiing you not care about a single fucking thing, be unwilling/unable to think, and possibly inducing black, death-like sleep and/or motion dyskinesias/tics. I can't remember reading anything that suggest widespread blockade of the dopamine/5ht systems is good for any sort of drug dependence. Maybe for an out of control acid trip, or a schizophrenic meltdown, or sedating someone as a last-resort, but not GHB dependence.



> MXE has a stronger affinity as a DRI and is blocking the amphetamines.


On trhe topic of MXE, I think it's a damn strong DRI & definitely not an "anti-addictive" agent any more than PCP/ketamine is. (Probably due to this property,) I have also seen it precipitate quite the washout similar to cocaine when overused or used in naive individuals (probably in combination with stimulants)... consisting mainly of inattention, head fog, & sleepiness. 6-24h after last dosing Relieve it with a solid dose of caffeine if you have to work.


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## MeDieViL

Yes every dose; and i really mean abscence seizures like my girlfriend sees me shouting making repetive movements and other seizure related things.

Minocycline or ginseng prevented this from occuring tough.

Apoligizies; indeed stims related posts i usually dont post much when sober:d ill try to remember to edit my posts.


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## MeDieViL

That anecdote comes from a person that was previously addicted; you are correct that just a few doses a day likely wont produce much tolerance.
(apologies forgot the edit function again)

"You can ride that coaster every day until you no longer find pleasure in it"
I do not consider this possible as recreational drugs directly induce pleasure; thus if they keep working pleasure will allways be found.

True ibogaine works on a shitload of differend pathways; there are so many involved in tolerance; nmda is just one of many.


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## thikal

> Anecdote of a personal friend says that DXM allowed GBL to stay working well; its possible DXM is more effective for GBL perhaps give that a trial run and eventually amisulpiride. Id be curious for your results.



DXM at 60mg gave me a great mood lift when I tried it for tolerance when I abused GBL. I don't know if it is due to his serotonine reuptake inhibitor proprieties or/and to his NDMA antagonist proprieties (certainly boths). But i'm asmathic so it's not ideal for me, just took 1 week 2x60mg a day DXM. DXM or memantine on me keep the dose really low, but I clearly don't have the almost empathogenic/stimulant proprieties than I had at the beggining, and It can be explain that my GHB receptors are fucked and aren't "healed" by memantine and other NDMA antagonist. Iboga may have an other action on GHB receptors tolerance. 

If I can find some amilsupride I will try it really slow and post my results. But this pharm have a shitload of side-effects and I don't know if it's really worth it. I read a little bit about this in the vidal, and I plan to take it at the low dosage (50-100mg/day) to avoid the antipsychotic part, but I'm not sure if the action I seek on GHB receptors take place at this dosage. 



> When tolerant to gbl it feels more sedating and far less euphoric this would indicate the problem is in the GHB receptor; G does indeed downregulate the ghb receptor wich amisulpiride upregulates again altough im sure GABAB downregulates as well.



I think GHB receptors take longer to reset because I don't have a physical tolerance yet (1,7mL and I'm sleeping like in the beggining), but don't have the euphoric part. Can you explain to me why amislpiride can upregulate GHB receptor and be an agonist GHB receptor in the same time? That's really interesting hehe! 



> Anecdotally its know the racetams potentiate several drugs (personally i experience massive mpa potentiation of mpa) however the racetams likely accelerate the formation of new tolerance (eg look up ethanol aniracetam) however one anecdote suggests that the combo of a racetam and a nmda antagonist offers the best of both worlds.



I tried piracetam with GBL, and without (more than a few months each) and didn't manage to find a real difference! Maybe I should try a more potent racetam, but my finances are low (that's an other problem hehe). A few months ago you weren't able to say if racetam stop the good effect on tolerance of NMDA antagonist, now you have evidences that there is no problems mixing them? I may be interested to read this anecdote because I was thinking on this question too!



> From what I have heard, GHB/GBL is pretty reliable in terms of producing effects, pleasurable or otherwise, unless dosed very frequently.(seeing as it's an endogenous n/t and all). 1-3x a day is probably nothing to worry about. I guess it varies between people.



You are totally right. I took GBL during 1 year three time a day most days in the week and didn't have a big tolerance or big issues, and after a shitload (for me) of MDMA in 3 days and the depression that followed, I started to take it around the clock and shit followed^^

Thanks to share you're knowledge sekio and Medivil it's really appreciated!


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## /navarone/

Epsilon Alpha said:


> *cough* just buy homotaurine *cough*
> Pretty sure the whole deal with acamprosate's N-acetyl group was to make it patentable seeing as homotaurine is found in several seaweeds.



Acetylation of the compound you mentioned probably prevents homotaurine from becoming a zwitterion and thus increasing direct bioavailability by not needing an amino acid transporter to cross the BBB (a la gabapentin style).

Also on PubMed I have found only 5 papers when searching "Homotaurine NMDA" and they all inevitably refer to N-Acetyl-Homotaurine and it's NMDA antagonistic potential. One of these studies also suggests that acamprosate has antagonistic activity at the metabotropic glutamate receptors.


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