# That Wacky Modafinil



## Hammilton

How would you classify modafinil?

It binds to DAT, increases MA levels, has odd H3 effects.



> There have been some preclinical studies of potential wakefulness-inducing treatments that work biochemically by inhibiting the histamine H3 receptor in the brain. However, modafinil has behavioral effects even in mice whose H3 receptor is genetically knocked out (6). It is possible that modafinil is working on the hypocretin system (7), a unique peptide neurotransmitter system that is abnormal in narcolepsy but is unlikely to be a key player in the biochemical mechanism of bipolar depression. Therefore, one could think of modafinil as a nonspecific or symptomatic treatment of bipolar depression.



hypocretin?  Never even heard of it until now.  Oh, it's orexin.

from wiki:



> Pharmacology
> 
> The exact mechanism of action of Modafinil is unclear, although numerous in vitro studies have shown it to increase the levels of various monoamines, namely; dopamine in the striatum and nucleus accumbens,[54][55] noradrenalin in the hypothalamus and ventrolateral preoptic nucleus,[56][57] and serotonin in the amygdala and frontal cortex.[58] While the co-administration of a dopamine antagonist is known to decrease the stimulant effect of amphetamine, it does not negate the wakefulness-promoting actions of modafinil. Modafinil activates glutamatergic circuits while inhibiting GABAergic neurotransmission. Modafinil is thought to have less potential for abuse than other stimulants due to the absence of any significant euphoric or pleasurable effects.
> 
> The central stimulating effect of modafinil shows dose and time-related features. The effect tends to be enhanced by chlorination but reduced by methylation. Modafinil blocks the reuptake of norepinephrine by the noradrenergic terminals on sleep-promoting neurons from the ventrolateral preoptic nucleus (VLPO). Such a mechanism could be at least partially responsible for the wake-promoting effect of modafinil.
> 
> Modafinil has a binding coefficient (Ki) of about 4,000 nmol/L for the dopamine reuptake transporter, and in excess of 10,000 nmol/L for the norepinephrine reuptake transporter.
> 
> A newly proposed mechanism of action involves brain peptides called orexins, also known as hypocretins. Orexin neurons are found in the hypothalamus but project to many different parts of the brain, including several areas that regulate wakefulness. Activation of these neurons increases dopamine and norepinephrine in these areas, and excite histaminergic tuberomammillary neurons increasing histamine levels there. There are two receptors for hypocretins, namely hcrt1 and hcrt2. Animal studies have shown that animals with defective orexin systems show signs and symptoms similar to narcolepsy. Modafinil seems to activate these orexin neurons thus promoting wakefulness. However, a study of genetically modified dogs lacking orexin receptors showed that modafinil still promoted wakefulness in these animals, suggesting that orexin activation is not required for the effects of modafinil.
> 
> It is possible that modafinil acts by a synergistic combination of mechanisms including direct inhibition of dopamine and norepinephrine reuptake, as well as orexin activation.
> 
> It has been shown in rats that modafinil increases histamine release in the brain, and this may be a possible mechanism of action in humans.[59]
> 
> Armodafinil a single R-enantiomer of modafinil was approved by the FDA for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder.



It seems to not be recreational, but all of mechanisms seem to scream recreational.  So why not?

I've taken it two days now (at 175, tommorow I'll go to 200 where I was supposed to start, but better safe than sorry- I was up until 3am last night), and I don't know that I could distinguish it from a low dose of amphetamine.  Definitely not like a DARI, which even at low doses I experienced euphoria, but with amphetamine I never did.  I don't have any euphoria, but it is still useful.

It's probably the most mentally boosting drug I've ever used.




Also, I've seen some 'modafinil analogues' of phenyltropanes made that were insanely potent; have similar things been tried for regular PEAs or is the ethylamine to short to stick the sulfur into?


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## negrogesic

That DAT affinity is quite low, so at "wakefullness promoting" doses there is little going on in terms of binding to the DAT. 

The stuff used to give me nasty headaches after 300mg's.


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## getreal

I took quite a bit of this stuff last year when my shrink Rx'd it for me.  I was always dead tired.
The first few days it was ok,thinking was cool, then up the anty and the bottle was gone


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## MurphyClox

> It seems to not be recreational, but all of mechanisms seem to scream recreational. So why not?


First, because none of those mechanisms completely explains modafinils action completely and all of them seem to contribute only to a very small degree. As Negrogesic elaborated, the affinities are somehow low with most targets.

It's just not "recreational" (how would you define the term?) because it doesn't do anything else than keeping you awake. There IS no euphoria, no increased sociability, no increased libido. None of the fun stuff that amphetamines are producing.

And additionally, as Negrogesic pointed out, if you go too far (IIRC 200 mg are the recommended dose, not 300) than you will only get headaches and other sideeffects. It sounds like the "perfect drug" (if such a thing even exists): It does what it is supposed to do but nothing else. How much else drugs are like this? Especially in the psychoactive field...

I remember to have read that it even takes some days of intake to develop its full activity. So, the abuse liability must be extremely low. It doesn't help to snort it. Has anybody here ever read about injecting modafinil?

Peace! Murphy


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## Mr TIMO

I've tried the indian brand modalert for the past few weeks, and i can't say i noticed it help my day time sleepiness at all.
the first time it seemed to help, but that may have been placebo.
but now it doesn't seem to do much at all at the 200mg does 

which is strange because most users comments are quite positive about it, so it makes me think maybe i've been given sugar pills...

im on ssri's if it makes a difference.

edit: murphy i just read what you said about it taking a while to develop full activity, i wonder if that's my problem?
i don't want to take this everyday, just on tired days like the start and the end of a week.


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## MurphyClox

Mr TIMO said:
			
		

> edit: murphy i just read what you said about it taking a while to develop full activity, i wonder if that's my problem?
> i don't want to take this everyday, just on tired days like the start and the end of a week.


I'm very sorry that I can not back up this with a reference but I'm quite convinced that you have to take it regularly for at least 1-2 weeks to feel the full effects. Taking it just occasionally (like it would be possible with amphetamine or methylphenidate, just to mention 2 examples) won't help.


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## Snowbear

IMO its only difference from a low dose of prescription amphetamine is little to no desire to keep re-dosing.

During the last few years I sold commercial real estate, a lot of people I knew took it to work long hours.

It helps me within 1.5 hours of the first dose.  Most friends who tried it reported the same.  (These were high stress environments where we had worked all day and were attending night meetings with investors out of town.)


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## MurphyClox

I honestly admit that I may have confused something here... I can't find _any_ hint that modafinil needs some time to fully develop its effects and until nobody else does so, I take my statement back. I have no idea how fast modafinil acts...

Sorry!


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## Snowbear

The doctors who prescribed it both said it took time also.  I think the manufacturer's reps stretch that point to doctors to make it sound like an "anti-depressant".  I think the info that came with the package said the same thing.


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## Hammilton

MurphyClox said:
			
		

> I honestly admit that I may have confused something here... I can't find _any_ hint that modafinil needs some time to fully develop its effects and until nobody else does so, I take my statement back. I have no idea how fast modafinil acts...
> 
> Sorry!



I noticed strong effect within 1.5 hours of my first dose.

My doc started me out at 200mg right away (though I started at 175 roughly) and I noticed greatly improved thinking clarity.  I've not had pure dexamp, but this definitely beats amp or methylphenidate as a nootropic.


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## nabollocks

I am interested to hear how modafinil interacts with your buprenorphine ham? I believe you may be getting some drug-drug related effects here. 

I was also prescribed modafinil for excessive day time sleepiness, and found it to be a perfect drug for that condition. However, do not mix it with caffeine as you will find yourself an anxious wreck, and going to the toilet all the time.


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## Hammilton

I actually don't notice any effects.  I waited 25 hours before taking my suboxone, and I'd usually have expected to feel quite sedated (on my first day of the modafinil) but instead I was rather awake and not really feeling the effects.

I dunno.

I took a 25mg booster at 4:30 this after noon, and I noticed quite a boost, I'm still feeling it.

What I love about this stuff though is that you don't know you're on a drug really.  If you're doing something that requires your concentration, you can't really notice.

Definitely second the caffeine thing.  I like mixing a little mountain dew into my sierra mist in the morning, maybe 1/8th of the glass is md the other 7/8th mist.  I was sweating and anxious.  Yuck.


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## Riemann Zeta

> I've tried the indian brand modalert for the past few weeks, and i can't say i noticed it help my day time sleepiness at all.


Unfortunately, modafinil may be one of the only true examples of a generic being vastly inferior to the brand-name formulation.  The interesting thing about modafinil is that it is absolutely insoluble in water and is not very well absorbed by the body unless the pill is formulated in a particular way.  The company that designed it, Cephalon has a bunch of obscure patents discussing the "particle size" of recrystalized modafinil in Provigil tablets--apparently the compound is only particularly well-absorbed by the gut if the tablets are made in the special "trade secret" way alluded to in the patent.  That's my explanation of why generic modafinil sucks ass.  I've tried a whole bunch of it--the real brand is insanely pricey (as a psychiatrist once told me: the only major side effect of modafinil is the large hole it leaves in the wallet)--and it never worked as well the brand.  Perhaps try to *really* crush the shit out of generic modalert tabs in a mortar/pestle and put the powder into regular gelcaps?

Although I'm mainly a dextroamphetamine fan, I've been on it for years, never abused it and it has never let me down or given me any side effects.  If you abuse the shit out of dextroamphetamine, you are asking for trouble--and if you have that propensity but still want a decent stimulant, modafinil is an excellent option.


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## dunwich

Modafinil is great.

I am pretty sensitive to it. I have never taken over 100mg, and that was way too much. Normal dose is 25-50. I have noticed that sometimes doses lower than that seem to actually decrease my concentration. 

I have however been afraid to take it recently since i found out it can make your epidermis separate from the dermis in rare cases...sounds terrible.

Low doses of modafinil are quite nice with green tea ime. Coffee is a no. But even decaf makes me jittery...


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## Riemann Zeta

> I have however been afraid to take it recently since i found out it can make your epidermis separate from the dermis in rare cases...sounds terrible.


Zuh?  I'm never heard of anyone having all their skin fall off from taking modafinil.  Maybe someone had one of those super allergic reactions (called Stevens-Johnsons disorder, or something like that), resulting in severe rash and epidermal necrosis?


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## negrogesic

I was recently prescribed Desoxyn tablets, and at low dosages it has the nootropic like properties of 200mg of modafinil. I took 15mg of the Desoxyn yesterday, and it did not give that nasty zombified "must do something" feeling that I get from 15mg of d-amphetamine. I am prescribed 20mg a day, but in actuality I will probably take 5-15mg, _once every ten days_ (at most). Plus, I really don't think it would be healthy to take such a potent releaser of dopamine everyday, even at the lower dosages. 

Also, the Desoxyn is _considerably _ more expensive than even the brand name Provigil. Believe it or not, the Desoxyn was my doctors suggestion (after I told him that I was unhappy that pemoline was no longer available, as it felt it had been more centrally acting than d-amphetamine).

Needless to say, from past experience getting "high" on methamphetamine actually sucks for me so I don't feel any need to abuse/misuse.  I may eventually go back to Provigil.


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## MurphyClox

Quoting Wiki here:


> From the date of initial marketing, December 1998, to January 30, 2007, FDA received six cases of severe cutaneous adverse reactions associated with modafinil, including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) involving adult and pediatric patients.



If necessary, I can provide some publication on this issue. The reports are rare but confirmed to my knowledge.

@Dunwich: If you have taken modafinil for a longer period and haven't noticed any allergic (skin-)reactions or whatsoever, you should be on the safe side. If those side-effects didn't occur yet, they are very unlikely to occur now.

About the solubility/bioavailability-issue:
What about the prodrug Adrafinil? I guess that a hydroxamic acid is somehow better soluble. Any comments here?

Peace! Murphy


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## dunwich

MurphyClox said:
			
		

> @Dunwich: If you have taken modafinil for a longer period and haven't noticed any allergic (skin-)reactions or whatsoever, you should be on the safe side. If those side-effects didn't occur yet, they are very unlikely to occur now.



Yeah i assumed that it already would have happened, but I have gotten some nodular acne type stuff from modafinil.  I think. It hasnt happened in a while and the acne was  perhaps caused by using l-meth and propylhexadrine inhalers.


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## Riemann Zeta

^^ You might be allergic to the compound then (if the acne is really modafinil-related, which, as you mention, you can't be sure of yet).  Modafinil has a sulfa moiety and is metabolized to a sulfonyl compound, which some people can be highly allergic to--they get rashes, hives, etc... Stevens-Johnsons disorder (epidermal necrosis) is the result of a *severe*, dangerous and potentially life-threatening allergic reaction.  Luckily, it is extremely rare, but you hear about it every once and a while, when someone turns out to highly allergic to a given drug.  For example, there are cases of severe allergy to the anticonvulsant/mood stabilizer lamotrigine, but I've been on it for years with zero problems.  So a handful of allergy cases does not usually indicate that the drug is specifically harmful to the population at large.


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## Hammilton

I'm severely allergic to Lamotrigine.  First dose nearly killed me.


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## Riemann Zeta

Yikes.  I guess that is why it has a black box warning about allergic reaction.


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## grue

Interestingly, I exchanged some messages a while back with a guy who said he experienced "cocaine-like" euphoria lasting all day long from the combination of modafinil and cabergoline.


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## hexxx

My shrink and neurologist won't let me near the shit. But they'll give me tons of fent, clobazam, dorminoct and lyrica. Stocked up. Even double the dose of fent at the drop of a hat. I want something to boost my cognitive functions. I believe I have PCCI but I can't get shit for it. Lyrica doesn't help my condition at all but it's necessary for neuralgia. 

They are convinced that Provigil is the devil, addictive and unnecessary. Maybe they are right and I should wait for the rest of the stuff to ware off. But in the mean time I'm a professional engineer trying to put my life back together after 2 major mishaps, I have to have my act together at the drop of a hat when my boss comes marauding into my office with some problem they don't know how to solve.

Also regarding the post RE: Generics and the adsorption matrix, none of the specialists seem to want you to use generics at all. I had a theory about stereoisomirsm being the culprit and they told me the same thing after a bit of pressing, they mentioned photographic molecules rotating and racemic mixtures (obviously stereo-isomerism but all I could do is act dumb).

I don't know if they are being brainwashed or paid off by the pharm co's.


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## grue

> ]My shrink and neurologist won't let me near the shit ... I believe I have PCCI but I can't get shit for it ... They are convinced that Provigil is the devil, addictive and unnecessary.



Just ask them for Desoxyn instead.

No, but seriously, as far as I know modafinil is generally not viewed by doctors with the same hysteria that psychostimulants, even methylphenidate, often provoke ... and there's decent reasons for this, I mean even within the context of the world of law-abiding conservative doctors  ... your professionals seem by this metric to exist on a fairly retarded area of the curve.


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## MurphyClox

@Hexx: If there is one thing to be said about modafinil, then that this is hardly addictive at all. Even the other side-effects (escept for headaches) are seemingly rare.


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## nuke

Why not just buy adrafinil?  It metabolizes to modafinil.  There's stuff warning that it can elevate liver parameters but all the tox I've read about modafinil indicates this too and that it does not indicate toxicity or carcinogenicity despite causing liver enlargement.  Not to mention it's cheaper.

I think the entire reason for modafinil's controlled subtance status is that it helps the doctor-pharmaceutical industry axis make more money; it doesn't appear to be all that much more self-reinforcing than caffeine in primates.


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## bluedolphin

Adrafinil is an inferior stimulant compared to Modafinil. I notice more amphetamine-like peripheral side effects, for example, runny shits and muscle tension. The "buzz" (yes a mild buzz) is also not as smooth feeling.

Modafinil was nice the first day... until I couldn't sleep even 16 hours later... somewhat nice the 2nd day, and by the 3rd day I basically just took it because I was so tired from taking the drug and getting shitty sleep the first two days. On this third day I had a mildly negative reaction to the drug (200mg) as I felt physically exhausted by my brain was oddly and unpleasantly awake alongside a shitty headache.

I have no Modafinil left and a few Adrafinils. I have no plans to take these ever again but I keep them just in case there is some occasion that I really need to wake up for. (I don't use coke or speed anymore.... and honestly I'd rather drink some coffee than take Adrafinil or even Modafinil)


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## <pyridinyl_30>

I hate to say this out loud and risk being flamed, but Modafinil is simply not worthy to be called a stimulant.  It's that lousy.


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## Hammilton

Modafinil addictive and unnecessary?  Bah.

no evidence about that.


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## Hammilton

<pyridinyl_30> said:
			
		

> I hate to say this out loud and risk being flamed, but Modafinil is simply not worthy to be called a stimulant.  It's that lousy.



Have you had the brand name by chance?  It's definitely wake-promoting.  Not in that faster faster faster DARI sort of way, but definitely restores alertness and awakeness (???) far better and with far fewer side effects than caffeine.

I've never had a headache or anything else though from it.

I do notice that if I try sleeping on a dose I end up in this half sleeping state populated entirely by odd dreams.  Not a bad place to be- but when you have 3 hours of this out of an 8 hour night of sleep, you're not getting enough real rest!

I took 225mg today at 730a and at 335p I'm still feeling it quite strong.  It's not really anything though.  Definitely hard to categorize.

I don't think it enables you to work faster, but there's some intangible nootropic effect.  I practiced some 3D maneuvers today (hovering, torque rolls, harriers and rolling harriers, things I'm not too good at.  I did much better than I ought to have though.  Defintely beyond my capabilities, but I watched some videos to give me some tips, and it definitely aids the learning capabilities.)


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## ebola?

A single datum:

I've used modafinil for occasional performance enhancement when running a sleep debt, mostly in academic settings.  It does what it claims very well.  It feels to me almost like caffeine with NO peripheral effects, maybe with a bit more of a concentration boost...but no euphoria or motivational enhancement.

One day, I was so drowsy that I accidentally doubled my dose, from 200 mg to 400.  After failing to induce vomiting, I braced for a yucky ride.

There wasn't one.  I merely experienced extended duration.

So odd.

ebola


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## <pyridinyl_30>

Modafinil, to me, felt like a large intravenous infusion of cool saline solution, somewhat comparable to psuedoephedrine--not unpleasant, though largely worthless.

I shouldn't say it has no use though or is totally worthless, but I don't think you're going to see me trade in my once daily amphetamine prescription for provigil anytime soon.

Perhaps Hammilton is right and modafinil is actually, like the racetams, a nootropic; if that is the case, however, I will have been right not to classify it as a stimulant to begin with.


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## Hammilton

Give it a shot when you've not slept for 20 hours (not due to drugs!) and tell me you think it's entirely without wake-promoting properties.


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## Xorkoth

I was prescribed Provigil/modafinil for a little while.  At first I would take a 200mg pill and not really notice anything.  At the time I was heavily sleep deprived and just kind of a mess.  Then much later I rediscovered my leftover prescription and took a 200mg pill, and was floored with overstimulation and anxiety, really nasty.  But I tried some more with lower doses and found that 25-100mg would make a great functional dose.  It provided me with a very, very light euphoria and motivation.  At 100mg I started to become stimulated, but not in a warm, friendly way, so I never raised the dose higher than that again.  I found that if I mixed it with a LITTLE BIT of caffeine, like 25mg or something very small, it combined favorably and got me feeling a little bit nice.  But it was very, very easy to overdo it and get disgustingly overstimulated.

Overall I wish I still had some for those days where it's hard to get going.  I found it to be a very clean and effective stimulant with very little potential for abuse, and I tend to abuse things.  It wasn't anything exciting, but it was nice.


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## Riemann Zeta

As a person with ADD, would I trade in the Dexedrine XR that I have taken daily for years for modafinil?  No.  Do I appreciate the ability of modafinil to resurrect me from a disgustipated mental state if I have been unfortunately without sleep for more than 24 hours (due to circumstances, not due to being spun)? Hell yes.  

And I would also argue that some people with ADD might respond well to it.  I respond extraordinarily well to amphetamines and not so well to dopamine reuptake inhibitors (e.g. methylphenidate just stopped giving me decent effects and really only made me tired).  I guess you just have to give it a fair shake.  I think it would be great for people that might have a temptation to abuse something like Dexedrine or Adderall, because modafinil has demonstrated to be quite abuse-proof (I think it is stupid that it is classified as a C-IV in the US...and it is only classified as such because it is technically considered to be a stimulant).


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## Hammilton

Yeah, I think when the FDA/DEA saw that it bound to DAT and cocaine habituated primates would self administer, they figured humans would too.

It's odd, because it didn't work very well for cocaine habituated humans, though it does dull the euphoria from cocaine.


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## MurphyClox

I completely second Riemann_Zetas last post!

In Germany, modafinil was even *un*scheduled in march this year. That strongly supports the low potential for abuse as officials here are not really prudish when it comes to forbid some psychoactives.

Murphy


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## serotonin-system

For me on the initial doses it was deffinitly stimulating and euphoric. 200mg on a night on the piss and I was far more outgoing, confident and jokey. The next day though I did realise I said things I regretted. It made me far more likely in my pissed up state to take the piss out of people and be cheeky. 

After 2-3 times though that effect subsided and after 6-8 goes it's completely gone and I wouldnt take it on a night out again. Now if i use it for academic work I do find it stimulating, gives me anxiety, a headache and diarhea. Though granted I almost always mix it with coffee. I've got a mountain of academic work at the moment and am desperately trying to find some ritalin or adderall, but I live in the UK.....U americans are so lucky. Adderall, Dex, ritalin, loads of pharmacuetical opiates all at hand.


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## MurphyClox

I wouldn't call ritalin "at hand". Isn't it scheduled?!


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## Hammilton

yeah, schedule II.  However, our psychiatrists are far more liberal about prescribing adderall and ritalin.

They're generally more liberal about opiates, but only to a degree.  It's easy to get a small count, no refill bottle of vicodin or T3, but I think equally difficult to get a long term prescription for these or anything stronger.

I think more people luck out and get really good stuff forever for no reason here, too, though.


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## coriolis

In the past I was taking modafinil 200mg q.i.d. sometimes even 1200mg or 1400mg daily and 100-200mg of quetiapine hora somni for the ensuing insomnia. I took such large doses for about 3 months and I felt well-it helped to compensate my cognitive deficit due to mainly idiopathic encephalopathy. But after this period I got constant sore throat and flu-like feeling-perhaps a some blood dyscrasia appeared.


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## MurphyClox

Holy...! 1200 - 1400 mg daily is by FAR more than recommended! As was said earlier, modafinil (almost) lacks any real stimulating property. It keeps you awake, but doesn't provide the pushing like amphetamine and alike. Why did you take such high doses? Did it change the "high" to some degree?


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## nabollocks

MurphyClox said:
			
		

> Holy...! 1200 - 1400 mg daily is by FAR more than recommended! As was said earlier, modafinil (almost) lacks any real stimulating property. It keeps you awake, but doesn't provide the pushing like amphetamine and alike. Why did you take such high doses? Did it change the "high" to some degree?



I have been there once... just in the name of science.

Needless to say, I did not sleep that night. 8) 

The experience was sort of self regulating. Like my brain was telling me that it did not require any more of the substance. Definately not a nice feeling, and all i wanted was to be normal again.


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## Riemann Zeta

Above 400mg or so, modafinil is all side effects (mainly headache, dizziness and stomach discomfort) and no additional beneficial CNS stimulation.  So, as mentioned, it is pretty 'self-regulating.'


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## hexxx

Hammilton said:
			
		

> Modafinil addictive and unnecessary?  Bah.
> 
> no evidence about that.



I wish my doctors thought that way, a psych *and* a neurologist have both told me that (pretty much), I'm dying for some stimulation. All I have at hand are depressants and I really want Modafinil to help me get up in the morning and concentrate. It is S5 here, same category as benzos and relatively strong painkillers (CIII in US).

Even while I was asking at pharmacy for possible help with concentration because of high Lyrica use, they immediately said to speak to my doctor about Provigil and gave me the box instructions without batting an eyelid. I was hoping for some nootropics or something but they are actually scheduled here (nootropil is S3 - which means you normally need a script or they may hand them to you without a script if you give them a story, diclofenac is the same although they normally just hand that out).

I have one doctor left to try and get it from but he's a oncologist and I won't see him for a few months. I don't know if he'll buy the PCCI story, he was strict on meds even when I had cancer... My psych told me to ask him so maybe there's hope. The psych wouldn't even RX nootropil because he said it's useless and told me that there is evidence of dimentia from Ginko Biloba usage - maybe he just thinks I'm really fucked up? 

EDIT: I think the psychs getting high off his own supply. They tried to use ginkgo to treat dementia, it doesn't cause it.


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## Kudos

Modafinil seems severely underrated. In my experience using it, it has proven to be the overall superior stimulant. In terms of wakefulness, it's the only thing short of opiates that makes reasonable sleep deprivation close to bearable. Getting little to no sleep results in complete anguish for me; my body temperature plummets, my brain completely shuts off, my skin gets oily and all my muscles hurt. In a word, it's torture. Amphetamines just cause further damage, though it keeps me from toppling over; caffeine decimates the glycemic index (I'd be better off just eating fruit).  Most noteworthy, the energy modafinil gives stands in stark contrast to that of Ritalin, speed and the like. It is far more easy-going, friendly, playful and visceral than the cerebral, analytical, often arrogant, cocky etc. equivalent of these others. As a result, I have found it inferior to Ritalin for strictly intellectual activities requiring """ADD""" suppression, but far more practical for regular use. I'd consider it a far superior replacement for daily caffeine. 

However, Modafinil also seems to be a far superior anti-depressant (for what we'll call my 'depression), than any anti-depressant, anti-psychotic, benzodiazepine, etc. etc. It has been more productive in that regard than anything short of hallucinogens, and, assuming I am not some lone freak brain, it is practically a scandal that it has not been researched more thoroughly for this type of treatment. 

It would be very nice to have more information about its mechanisms, especially for the purpose of finding similarly great chemicals :D.


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## death_kitten

*My expirence with Modafinil*

First off, I have narcolepsy, which was diagnosed about 2.5-3 years ago and due to factors beyond my control, I had to change doctors and was unable to be on my full set of meds for some months.  Now, however; I am back on my full script regimen (with limited exceptions to be explained later) of Dextroamphetamine: 30mg twice daily (max legal dosage), Modafinil: 200mg twice daily, Fluoxetine: 20mg twice daily, and Temazepam: 10mg-20mg as needed...  On top of all that I drink any energy drinks I can get my hands on and smoke 1-2 cigs every three days or so (working on trying to quit, but not working so well), and given all of that, I can still fall asleep during the day usually.  Now, the pharmacy that I have to go through to get my meds has a bunch of extra regulations on how they handle Schedule II medications, which means that in the past in the past year, I have not been on my Dex for a total of a month because of the incompetence of their staff and sheer absurdity of their Schedule II medication refill system.  So I called my neurologist and asked him what to do and he said to use the Modafinil as needed and he would refill it early, one of the days I got up to about 2g through out the course of the day.  Given it was a day that I had to go out and do stuff like drive and interact with people and such, cause the last thing I wanted was to fall asleep while driving or something.  The only additional effects that I felt on this high of a dosage was a slight increase in paranoia, muscle tension (especially in my neck), and the normal effects were increased slightly, though I still got a full night of sleep that night.

Now, as for the standard effects that I have noticed while on this medication are that it does promote a state of being awake, it seems to help with my problem solving abilities and a slight increase in the speed at which I can react to situations (or perhaps my brain just subconsciously assesses the situation and the increase in problem solving affects that, I don't know.  All I know is that I can have my arms full of groceries, drop a bottle, and catch it before it hits the ground and without dropping any other items.)  One other effect that this substance has (it seems to affect depressants in this way as well as stims, though I don't have enough experience on that side to fully verify this theory) is that it seems to synergize with and amplify meds/chems that act on the CNS in general; it definitely does this with CNS stims from my expirence.  Which partially explains the ill effects many people have when mixing with caffeine, it would probably feel a lot like you were experiencing some degree of a caffeine OD, and those are just nasty.  One last note, the way that I have described how Modafinil feels when it is active is that it has a very "clean and almost clinically sanitary feeling" to it, where for me Adderall (I was on that before I had to change docs) felt kind of "fuzzy and tacky" and Dex just feels "edgy" comparatively.  Hopefully that helps a bit, and if anyone has questions, feel free to ask and I will do my best to help answer them.


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## nordr

death_kitten said:


> First off, I have narcolepsy, which was diagnosed about 2.5-3 years ago and due to factors beyond my control, I had to change doctors and was unable to be on my full set of meds for some months.  Now, however; I am back on my full script regimen (with limited exceptions to be explained later) of Dextroamphetamine: 30mg twice daily (max legal dosage), Modafinil: 200mg twice daily, Fluoxetine: 20mg twice daily, and Temazepam: 10mg-20mg as needed...  On top of all that I drink any energy drinks I can get my hands on and smoke 1-2 cigs every three days or so (working on trying to quit, but not working so well), and given all of that, I can still fall asleep during the day usually.  Now, the pharmacy that I have to go through to get my meds has a bunch of extra regulations on how they handle Schedule II medications, which means that in the past in the past year, I have not been on my Dex for a total of a month because of the incompetence of their staff and sheer absurdity of their Schedule II medication refill system.  So I called my neurologist and asked him what to do and he said to use the Modafinil as needed and he would refill it early, one of the days I got up to about 2g through out the course of the day.  Given it was a day that I had to go out and do stuff like drive and interact with people and such, cause the last thing I wanted was to fall asleep while driving or something.  The only additional effects that I felt on this high of a dosage was a slight increase in paranoia, muscle tension (especially in my neck), and the normal effects were increased slightly, though I still got a full night of sleep that night.
> 
> Now, as for the standard effects that I have noticed while on this medication are that it does promote a state of being awake, it seems to help with my problem solving abilities and a slight increase in the speed at which I can react to situations (or perhaps my brain just subconsciously assesses the situation and the increase in problem solving affects that, I don't know.  All I know is that I can have my arms full of groceries, drop a bottle, and catch it before it hits the ground and without dropping any other items.)  One other effect that this substance has (it seems to affect depressants in this way as well as stims, though I don't have enough experience on that side to fully verify this theory) is that it seems to synergize with and amplify meds/chems that act on the CNS in general; it definitely does this with CNS stims from my expirence.  Which partially explains the ill effects many people have when mixing with caffeine, it would probably feel a lot like you were experiencing some degree of a caffeine OD, and those are just nasty.  One last note, the way that I have described how Modafinil feels when it is active is that it has a very "clean and almost clinically sanitary feeling" to it, where for me Adderall (I was on that before I had to change docs) felt kind of "fuzzy and tacky" and Dex just feels "edgy" comparatively.  Hopefully that helps a bit, and if anyone has questions, feel free to ask and I will do my best to help answer them.




Quoted for absolute truth.  I'm an on-call analyst at a financial firm (you can imagine what that's like these days... and no I didn't get us into this mess, I work in the side of the business that cleans up after these kinds of messes), and suffer from basilar-type migraines.   As such, I'm on a battery of meds to combat that, as well as Alprazolam to help me sleep at night.  Naturally, I wake up groggy as fuck.  I was prescribed Provigil (name-brand, no generic shit here) a week ago and I can already notice a difference.  I don't feel like superman, I don't have the urge to type 90WPM, but I *do* socialize much better, I *do* detect a subtle increase in my cognitive function, and I find that it completely offsets the stupifying effects of Topamax.  I have also managed to work 6 hours straight on a mind-numbing report, whereas my usual ADD-self would be checking Bluelight or Google Reader every ten minutes.

Provigil is a drug designed to solve a problem, not to help you escape.  It has been an absolute godsend for me.


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## LuxEtVeritas

^indeed it can be for those who respond well and find the right therapeutic dose


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## irobeth

I've been taking 200mg/day for about two weeks now, and here's my take on it:

Modafinil lets you ignore exhaustion, both physical and mental, and nothing more.

Recently I was out on travel and took 200mg/8 hours, I was awake for 80 hours with no negative side effects until i discontinued the dose so I could get some sleep, at which point the classic signs of sleep deprivation kicked in. There was, after about day two, a haze of sluggishness which I would attribute to the body being worn out, but it didn't stop or hinder daily function - it was very easy to compensate for that lag by thought.

The first day I started taking them, I was capable of great physical exertion (high difficulty DDR for 6 - 7 hours nonstop) only to realize the next day that I had hurt myself doing it; I haven't tried anything like that since because I'm still getting used to actively listening for signals that I'm approaching a threshold for safety.

It'd seem the function of Modafinil is to let you shut off the alerts your body gives that you're reaching your limit. That's not necessarily a good thing, but it does allow you to debt yourself in the future for performance in the present. It's true that the drug itself doesn't push you, but if you've got the will it lets you push yourself.

I can't say that it's addicting because more often than not, discontinuing it is a welcome break from always being active. It isn't fun or unfun to use; It's just 'there' when you need it, minus the two or three hours it takes to pick you up. Taking it with caffeine makes up for its delay, however.

As for problems sleeping, I find that 25mg diphenhydramine seems to abort its wakefulness effects.


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## Riemann Zeta

^^ That's a good way of describing the effects of modafinil in situations where running with little sleep is the only option.  It does have a way of ameliorating the nasty-feeling side effects of sleep deprivation, both mental and physical.  In the context of lack of sleep, modafinil does not provide you with an 'amped' feeling, but (to some extent) does compensate for the sleep loss, making you feel relatively normal.


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## pofacedhoe

Hammilton said:


> How would you classify modafinil?
> 
> It binds to DAT, increases MA levels, has odd H3 effects.
> 
> 
> 
> hypocretin?  Never even heard of it until now.  Oh, it's orexin.
> 
> from wiki:
> 
> 
> 
> It seems to not be recreational, but all of mechanisms seem to scream recreational.  So why not?
> 
> I've taken it two days now (at 175, tommorow I'll go to 200 where I was supposed to start, but better safe than sorry- I was up until 3am last night), and I don't know that I could distinguish it from a low dose of amphetamine.  Definitely not like a DARI, which even at low doses I experienced euphoria, but with amphetamine I never did.  I don't have any euphoria, but it is still useful.
> 
> It's probably the most mentally boosting drug I've ever used.
> 
> 
> 
> 
> Also, I've seen some 'modafinil analogues' of phenyltropanes made that were insanely potent; have similar things been tried for regular PEAs or is the ethylamine to short to stick the sulfur into?



speed to me feels so boring like i'm in an office photocopying my soul till it erodes for sure but ritalin is euphoric creative rave up (MAKES ME FEEL SEXY AND STYLISH). the wonders of individual brain a neuron genetic styles

daris all the way but as for dopamine it may just miss the reward pathway and loiter somewhere pointless like shattners basson

this drug sounds usefull if you get tweaky of dex, it may not get you high but you can hold down a job-an actual decent result and positive long term gain(during moneygheddon)



  moneygheddon-  charlie brooker coined this term to make the financial climate sound bad but exciting rather than just plain old shit. remeber the chinese have crisis and oppportunity the same word.


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## Riemann Zeta

Crisatunity.


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## Solipsis

I see people are trying not so modest amounts through oral administration - probably tablets?
Might be worth mentioning that I have gotten excellent results from insufflating absolutely tiny amounts (in the order of 20 mg) pure product of course - the effect is absolutely instant and it only builds up more in the course of a couple hours. I don't understand because it shouldn't be water soluble?? Hmm.
I wouldn't call it a typical stimulant by any means, it facilitates the mere possibility of mental concentration and wakefulness as opposed to most stimulants that directly result in stimulation.
Little amounts of dextroamphetamine are used for AD(H)D and while I have only 1 experience with it I feel simultaneously more sedated and energized i.e. I have a clear head and a clear body, both can handle more activity though the direct effect is being LESS active!
Now, from modafinil I don't get less active but hopefully you see my point.


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## irobeth

Solipsys said:


> I see people are trying not so modest amounts through oral administration - probably tablets?
> ...
> Little amounts of dextroamphetamine are used for AD(H)D and while I have only 1 experience with it I feel simultaneously more sedated and energized i.e. I have a clear head and a clear body, both can handle more activity though the direct effect is being LESS active!
> Now, from modafinil I don't get less active but hopefully you see my point.



I've got 200mg tabs, yeah.

As far as clear head and body go, after about a month of prescription use, I'm noticing that I feel 'dirty' or 'hazy' in both mental process and physical clarity. Can't put my finger on it.


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## coriolis

As to the modafinil's capability of enhancing the efficacy of mental work I would say that modafinil makes me alert yet my mind is easily distracted, as to the amount of significant work I am able to do, methylphenidate is much more efficient, methylphenidate makes me focused and although it has the drawbacks of a "comedown', unlike modafinil, it can be attenuated by dosing it prudently in small amounts.


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## coriolis

Also be careful of combining modafinil with quetiapine especially in combination with oxandrolone. I don't know if it was only some exceptional drug idiosyncrasy but after this combination I suffered a severe hypertension, tachycardia and pyrexia, only sufficient dose of clonazepam and metoprolol saved me from an urgent visit to a hospital.


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## Ximot

also be careful when combining modafinil with psychedelic phenethylamines (2ce/2cd come to mind). sensory hyperstimulation was felt so acutely that I wasn't too sure if that was my mind or my body that was going to explode there. Due to the nature of modafinil, i wasn't even freaked out per se ... almost interested at how I was being pulled apart at the seams... didn't check bp or anything but it did get me to ingest an emergency helping of ghb . . .


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## egor

^I had a really bad experience with modafinil and 4-aco-mipt recently too...


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## Solipsis

Thanks for the heads up, probably when I'm in a condition to use psychedelics I should not have any need for modafinil but I will definitely pay attention to abstaining from the combination to be sure.

Oh wow, I'm really impressed with this stuff! I can eat on it, sleep wasn't a problem although I didn't take any further in the afternoon - there are no peripheral effects remotely strong enough to annoy me and in the course of peak plasma builing up over the first few hours there is a very very definite mood lift hinting to euphoria but about 10 times more natural than any other stimulating substance I've come across.

I've gotten about 1,5 g from a friend who often falls asleep right after taking it!
Hm weird.

A perfect piece of pharmacological wonder if you ask me!

(and it has a nice aroma too LOL)


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## Ximot

yeah it does have a weirdly nice aroma, and no pain when snorting whatsoever. I love snorting tiny bumps. i have to say that of all the drugs i have tried over the years perhaps modafinil is the best one... it is a godsend for a tired mind. in combination with alcohol, caffeine and ketamine it is most wonderful, even euphoric. I much prefer it to speed or coke or any of the cathinones. 

if I had to choose between modafinil and psychedelics, atr this poitn in my life I might well choose modafinil. To me it works like an anti-depresant and a stimulant at the same time.

It softens the edges whist at the same time sharpening the contours.

SOmetimes i wonder why, for so many years, I was so drawn to psychedelics. After my 2c-moda mishap - which was only just yesterday - I have to say that it seems I have gotten all i can from psychedelics... been saying that for 2 years already, but almost every time I do a psychedelic, i am reminded of that... they keep sending me the same message, and i have seen it all before. Why keep calling if I don't heed the message anyway? At least with modafinil I can get things done in the physical realm. That's worth something too. A lot, for someone as phlegmatic as me.


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## sunyata

does it give people nausea at all? I really hate nausea especially when I need to work (one reason I have love/hate relationship with coffee).

I'd love a caffeine replacement.


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## emarr

Love this stuff when I can only get 3-4 hours sleep and have to work the next day. It also seems to relieve some of the lagginess/fog I get from heavy night-time smoking (ironically, I mostly smoke to help insomnia...)


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## Ximot

@samadhisunyata:

no nausea for me with modafinil. have you tried switching to black tea or green tea for caffeine? Also WAY better than coffee. Add grated ginger to your tea as well to prevent nausea


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## wreckhead

Isn't anyone concerned about tolerance/withdrawal from modafinil?


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## irobeth

having taken modafinil for nearly two months, and now being off it cold turkey for about two weeks, I can say there are currently no notable withdrawal effects, nor was there an indication of tolerance during the time I took it.


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## Ximot

tolerance is not an issue. there might even be something like reverse tolerance, especially when snorted. there are also no withdrawals really. Maybe excess tiredness especially if one didn't get enough sleep while using it, which would basically be a form of abuse anyway and thus askign for complications. I used it a lot last spring/summer, then lost my stash during the sumemr and didn't retrieve it till a couple months ago. Must say that it's teh BEST PICK_ME-UP that I know and that I missed not using it. But there were no withdrawals.


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## irobeth

Ximot said:


> Maybe excess tiredness especially if one didn't get enough sleep while using it, which would basically be a form of abuse anyway and thus askign for complications.



The concept of fatigue doesn't really exist under Modafinil's effect, which isn't to say you won't still pay a price for exceeding your limits. Once I had been awake in excess of 80 hours without sleep and only shown a lowered dexterity (or perhaps a body->mind communication lag) Upon ceasing to dose regularly, everything came crashing down.

This suggests that while you are under Modafinil's effect, you are capable of ignoring any evidence that you're exerting yourself. It doesn't mean that evidence isn't there, or that you can't hurt yourself ignoring it.

This also suggests that after a long time of taking Modafinil, you may grow used to what you think is your capacity for exertion, and after ceasing it, feel deficient that you suddenly show resistance to such exertion.


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## egor

I've had no nausea with modafinil on its own, but mixed other things I have gotten nausea, namely my little misadventure with 4-aco-mipt and one other occasion when I needed a pseudoephedrine after taking it.


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## ASLEEP4DAYS

*Ive taken over the max*

I  was diagnosed with what they call excessive daytime sleepiness and was given modafinil it was tested on f-14 fighter pilots who were given 800 mgs a day and were kept awake 36 out of a 40 hour week and were said ti still be able to fly at a basic level 

i have personally taken 600 a day but it didnt continue to work for  me personally  so they augmented it with prozac but i had a bad reaction to prozac my skin was really dry and it was like having dandruff under my eyes 

i wanted to try straterra but before the b.c. medical will cover that i have to try dexedrine or whatever amphetimes they have , i have read of people using dex and modafinil togother , and although its not recomended by the doc or pharmacy , it seems to work for some .... 

as my doctor said your a phramacutiecl  nightmare or guinea pig then again are'nt we all as diffrent drugs effect diffrent peeps in diffrent ways


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## eatcod

Interesting the comments about bad experiences combining modafinil with psychedelics.

I've started a day with 200mg modafinil, stayed up all night taking MDMA, 4-HO-MET, 2C-D and alcohol, taken another 200mg modafinil in the early afternoon and then driven home early evening with no noticable side effects.


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## irobeth

Since this thread is already undead;


Modafinil seems to have interesting interactions with exercise (ignoring fatigue aside.) With modafinil I can sprint to a heart rate of 240+ and sustain one over 170 with no problems (until the next day when I'm exhausted) Are there guidelines on a 'maximum' heart rate? I've heard things like 220 - age; I'm 24 now and that means I 'shouldn't' be able to achieve a heart rate 192 or more.

With modafinil, my resting pulse is about 90. Without, it's about 58. I assume this is why it's observed to lower BMI in exercise control subjects?

Anyway; Did I just train my way into this range? Most people I mention it to are concerned that I can get it this high (modafinil or not)


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## ASLEEP4DAYS

I THINK THE best research on modafinil would be from the test's they did on  the soldiers considering there still using it today , i currently take 200mgs of modafinil and 20 mgs of dexedrine when i get up in the AM and 100mgs of seroquel at night , it seems to work for me at the moment , but i have an exceptionally high drug tolerance , so we will see , i'll keep you all posted


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## Mandark

Do you still maintain that there is no tolerance? I'm probably going to use modafinil extensively for the next few weeks and I'm concerned about it.


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## ASLEEP4DAYS

WHAT ARE YOUR CONCERNS  , the recommended maximum daily dosage is 400mgs .. i have taken double that  ...  if you exceed  the MAX  you should have a good heart cuz you can feel it for sure ,  and if you take any other drugs such as antideppresents , you have to be careful what you can mix with it , wellbutrin, or the patch , is a defenite NO NO  unless you enjoy seizure's , from my own experience it certainly does'nt seem to have any addictive properties


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## edarrin

> Isn't anyone concerned about tolerance/withdrawal from modafinil?




I've used it off and on for several years now (more than 5). I have stopped and started many times. That is the beauty of it. It just does what it's supposed to and nothing else. Great for professionals working long hours. I've never had any w/d t all from it. Actually I usually don't take it on the weekends when I do use it for extended periods without any trouble.


However, it is not recreational in the traditional sense at least.


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## prplNRGdrank1

Seizures with modafinil + buproprion? 

I'm taking 100 mg of modafinil + 300 mg buproprion XR... (+lithium)..
for ~13 mo. without noticing any seizures...and I'm fairly sure my doc isn't an idiot, but this worries me. 

Maybe the lithium's got enough of a neuroleptic effect...?
Is there any indication/evidence for modafinil + buproprion ==> seizure? I don't know enough about seizures or drug x drug interactions to tell, but I've never heard this before...


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## ASLEEP4DAYS

well i'm your evidence after i had a seizure then went and told an exp phrmacist and the psychitsrist  they both said  oh no  you cant mix those 2 , your doctors probably not an idiot but it does'nt tell him in the CPS book that you cant mix the two  .. you can mix prozac with modafinil as i was taking 400mgs of modaifinil and 30mgs of prozac and 200mgs of seroquel at night , before that i took effexor,celexa, then wellbutrin by itself ,, now what works for me is 200mgs of modafinil nad 20mgs of dexedrine and 100mgs of seroquel 

as what there trying to do is use one drug to augment the other or counter the effects ,, but they did attribute my seizure to the interaction of modafinil and wellbutrin


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## prplNRGdrank1

Oh, ok. Thanks for clarifying/expounding---I'm sorry that happened to you, that sucks.


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## ASLEEP4DAYS

ya  well  when i told my doctor he nearly shit , he started apoligizing  then babbled some greek  which was the first rule of medicine  ,,{ do no harm } even the first pharmicits  denied any liability as well ... both wellbutrin and modafinil are in a sense still fairly new on the market , wellbutrin was first used in the patch form to quit smoking they discoverd it also had some anti depressant properties , i was also taking a much higher dose of modafinil , but you may want to get a second opinion as falling on your head  is no fun at all especially when it gets trapped under your bed and your jerking around , i had some nasty rug burn


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## Silverfox

Mandark, I'd agree with edarrin. There have been times when I have taken 100mg modafinil (that's the dose that works for me) every other weekday for weeks on end, then when circumstances have changed none at all for weeks without even noticing.

When using it I find I only need it every second day because the day after taking it I feel unusually refreshed and clear headed.


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## irobeth

Silverfox said:


> Mandark, I'd agree with edarrin. There have been times when I have taken 100mg modafinil (that's the dose that works for me) every other weekday for weeks on end, then when circumstances have changed none at all for weeks without even noticing.
> 
> When using it I find I only need it every second day because the day after taking it I feel unusually refreshed and clear headed.




This is true _except_ if you take it long enough you will grow to expect that your capacity for work is always the same as if you are taking modafinil. I mean this to say if you aren't taking modafinil you will find that you are more 'weak' or disadvantaged in stamina.

As long as you aren't consistently overstepping your normal bounds while using modafinil you will be okay; just don't use it to reach places you otherwise couldn't.

Case in point: I am still hurting (broken, even) from friday's 5-hour sprinting fest.



About dose size:


> However, it appears to be higher than oral LD50 of caffeine. Basti and Jouvet ( 1988 ) describe a suicide attempt using 4500 mg of modafinil; the suicidee survived with no long-term effects but temporary nervousness, nausea, and insomnia



Modainil does release dopamine and norepinephrine, so it might make sense that wellbutrin would interact strongly with it.


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## ASLEEP4DAYS

i recall the suicide atempt it was a girl in cali she suffered tachaycardia {increased heart rate} where the immediate effects , you would have to expect that taking that much stimulant , im surprised her heart didnt explode


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## dokomo

Mr TIMO said:


> I've tried the indian brand modalert for the past few weeks, and i can't say i noticed it help my day time sleepiness at all.
> the first time it seemed to help, but that may have been placebo.
> but now it doesn't seem to do much at all at the 200mg does
> 
> which is strange because most users comments are quite positive about it, so it makes me think maybe i've been given sugar pills...
> 
> im on ssri's if it makes a difference.
> 
> edit: murphy i just read what you said about it taking a while to develop full activity, i wonder if that's my problem?
> i don't want to take this everyday, just on tired days like the start and the end of a week.



I have had two different indian brands (One was ModAlert and one was ModPro I think) and name-brand Provigil and I can assure you that name brand Provigil is far different from the Indian generics. I don't know if there is some enantiomeric contamination issues or something, but Provigil was hands-down the best one.


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## negrogesic

I had a strange experience mixing provigil will adderall; my vision was tinged orange, had a mild-anxiety attack, and felt overall quite dysphoric. 

I would imagine that if there no actual withdrawal syndrome, there must be some sort of rebound fatigue upon abrupt discontinuation after long periods of usage at dose.

Had a girlfriend recently (20 years old) who had been taking 250mg of seroquel/day for "bi-polar" disorder (despite never having any symptoms of the disorder other than "depression" as a 15 year old). Furthermore, she was also on varying amounts of tranxene, which she combated with 200mg/day of provigil. But, she was literally the best looking jewish girl i have ever seen (father was the jew, mother a blond). Still the neurosis from her father carried down to her and proved to much for me. Im actually 1/4 jewish but I can't stand the cultural, fear, neurosis etc. But like is said, literally the hottest jewish girl i've yet to see (tall order, I know). Kauft nicht bei juden. 

Figured this was relevant....


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## Silverfox

dokomo said:


> I have had two different indian brands (One was ModAlert and one was ModPro I think) and name-brand Provigil and I can assure you that name brand Provigil is far different from the Indian generics. I don't know if there is some enantiomeric contamination issues or something, but Provigil was hands-down the best one.



That is interesting, and something that I have heard reported elsewhere. I have only tried the branded Modalert from Sun Pharma, which I have purchased over the web but mostly directly from local pharmacies in India (for 1/10 the price!) and I have not experienced any quality issues with the generic product. However, I have found that tablets from the same batch can have quite pronounced differences in effect between doses. I do not attribute this to differences in composition but rather to differences in how the modafinil is working on me at that particular time. For example, one day 100mg might make me quite jittery and on another day really focussed and alert whilst some days I have to up the dose to 200mg ro have any effect. Has anyone else noticed such variation in effect?


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## Silverfox

irobeth said:


> This is true _except_ if you take it long enough you will grow to expect that your capacity for work is always the same as if you are taking modafinil. I mean this to say if you aren't taking modafinil you will find that you are more 'weak' or disadvantaged in stamina.
> 
> As long as you aren't consistently overstepping your normal bounds while using modafinil you will be okay; just don't use it to reach places you otherwise couldn't.
> 
> Case in point: I am still hurting (broken, even) from friday's 5-hour sprinting fest.



I understand what you are saying but I've tended to use it when living in Goa, where a combination of the heat, the susegade attitude to life and the numerous other distractions can make getting any work done quite difficult. Under those conditions I've found it makes a real difference to my productivity and general motivation. When I get back to the UK things work at such a different pace it is usually a month after my return that I notice I haven't reached for the packet.


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## drug_FUCKED

dokomo said:


> I have had two different indian brands (One was ModAlert and one was ModPro I think) and name-brand Provigil and I can assure you that name brand Provigil is far different from the Indian generics. I don't know if there is some enantiomeric contamination issues or something, but Provigil was hands-down the best one.



I 2nd that, i have purchased modafinil from various sources finding some brands upset my stomach and others cut with caffeine. Provigil is defiantly different to indian brands. I wouldn't use indian pharms too often as they have heavy metal contaminants and strengths often vary.


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## P A

> modafinil has demonstrated to be quite abuse-proof



Alone, maybe, but in combination with other stims (mostly cocaine, phenidate, and the like), many I know would beg to differ.

Any update on mechanistic stuff? I remember there was a negative study with orexin-knockouts. How about the whole "mobilization of intracellular peptides--->exocytosis of the gap junction" thing? That would probably better explain the indirect reuptake inhibition and the unique stim-potentiating properties...


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## Phener

*Summary of experience with modafinil:*

*Psychotic reaction(!)*

Went through a period of MASSIVE different types BENZO use, whilst taking MODAFINIL in the morning (reasonable high doses but not massive, i.e 600mg) all while having my nicotine patch (definately synergistic effect with modafinil or at least felt I missed/needed nicotine MORE when on modafinil, so much so I was using the high strength lozenges + patch). RESULT: After a month had what would best be described as a psychotic episode (proper paranoia, crazy thoughts, delusional thoughts etc) Coincided with a time when I could STOP take a few months off and recover. Horrible period in my life. 

Ever since then seem to have had a reverse tolerance to the compound (take it very occasionally) I.e take 50mg and thats enough to get me UP in the clouds + stimulated, ODD very ODD, I know appreciate it FAR more and use it very cautiosly when needed on the ODD occasion. 

(am totally fine now btw, no psycotic tendancys, never had them, all good)

Now thoughts as to the reason:
1) could have been the benzo's sending me bonkers with the modafinil simply allowing me to tolerate such MEGA doses +/- the NUMEROUS different types, Ironically after my morning modafinil was UP and away no sleepyness but then couldn't get toff to sleep at night so hence the MEGA doses of different benzos
2) Considered the pharmacokinetic interaction between  modafinil + some benzo's, some clinical evidence to suggest it speeds up metabolism (hence probably why it helped me WAKE up so well in the morning
3) high dose benzo GABA-A + Modafinil mode of action in CNS = BAD
4) atypical reaction to modafinil
*5) recently found out modafinil is a dopamine D2 partial D2, so placing bets on this factor being important*

*Interaction of some pro-drug opioids (codeine, dihydrocodeine)*

On seperate recent occasions there seems to be a definite mental potentiation of codeine but even more so dihydrocodeine. Was taking the paramol tablets (i.e just 7.5mg od DHC!) and they were having a BIG effect 

Reasons thus far explored:
1) modafinil induces CYP 1A2, 2B6, and 3A4 (explains many of benzo issues but trying to figure these one out - that just gets complicated!)

CYP3A4 responsible for codeine to norcodeine (no analgesic potential), thus leaving less codeine to be converted to fun compounds - so no go on that theory
CYP2B6 - explains the increased nicotine as known to be involved in nicotine metabolism but so far to my knowledge no effect on codeine/dihydrocodeine
CYP1A4 - ?no clues as to potential effect

2) Dopamine D2 partial agonism is synergistic with opioid intoxication
3) Mere mental simulation (I.e being awake) makes opioids more fun (upper downer theory)

Strange as in best ways to describe this feels like (especially with the low dose of dihydrocodeine 7.5mg) that effect is FAR more apparant than it should be. Wondering whether SOMETHING about enzyme inducing is increasing active metabolites. 

BEFORE self experimentors try the combination it was noted that it had no effect on high doses


----------



## longtimelurker

MurphyClox said:


> I honestly admit that I may have confused something here... I can't find _any_ hint that modafinil needs some time to fully develop its effects and until nobody else does so, I take my statement back. I have no idea how fast modafinil acts...
> 
> Sorry!



hi murphy. good to see you. i remember you from somewhere black.

i think you were thinking of piraceatam.


----------



## longtimelurker

my friend also bought some 'pure powder' from some well know place that deals in 'bulk'

of inferior quality to provigil and felt dirty according to him. i am yet to same this powder. 

i took modalert before an had no problems with it.


----------



## Silverfox

P A said:


> Alone, maybe, but in combination with other stims (mostly cocaine, phenidate, and the like), many I know would beg to differ.



@PA can you elaborate? Modafinil has been used clinically to reduce cocaine dependance as it competes for the DA receptor and has a much longer half life. My personal experince is that I have far less fiending for coke if I have taken modafinil previously.


----------



## phactor

I really enjoyed Modafinil for the time I was on it, I was just restarting college after a few years of partying and whatnot. I have ADD but do not want to take amphetamines. Modafinil was able to help me focus and pull myself together until I was able to turn that into a habit. 

Good stuff, worked great, didn't feel a thing (some jaw clenching the first few days), my appetite was okay and I was able to stop fine.


----------



## Heuristic

To throw in my .02:

I've used this for work purposes.  200mg has a tendency to give me a headache, and generally I used 100mg.


From what I've heard/read, this is potentially quite useful for those with ADD/ADHD; but obviously that's something to discuss with your doctor.

"Smart drug" issue: unless you actually have ADD/ADHD, this will have close to the same effect on your intelligence as any other substance marketed to make you temporarily smarter: marginal at best.  However, if you're suffering from a cognitive deficit due to sleep deprivation, it will reduce the extent of the deficit (with close to the same effectiveness as caffeine).

Still no long term studies: I'm a little wary due to this, since the lack of long term studies and the huge gaps in our knowledge about how this medication works and our brains add up to this: "we don't really know how or why, but modafinil has x positive effects; in the decade or so it's really been around, we haven't seen any negative effects other than y; if things go really badly in the future, we'll let you know."

I view it as an occasionally useful substitute for coffee, especially if I'm so tired that the doses of caffeine I take will come with the usual negative side-effects.


----------



## irobeth

Of interest: Modafinil substitutes for caffeine when in withdrawal

If all goes well I can quit caffeine and then discontinue modafinil (why?) without many issues.


Is there a reason one would ever discontinue modafinil? Maybe blood pressure?
I use it periodically to daily and haven't noticed a permanent trend on the blood pressure -- if anything, it's gone down.


----------



## MurphyClox

Heuristic said:


> I've used this for work purposes.  200mg has a tendency to give me a headache, and generally I used 100mg.
> 
> 
> From what I've heard/read, this is potentially quite useful for those with ADD/ADHD; but obviously that's something to discuss with your doctor.
> 
> "Smart drug" issue: unless you actually have ADD/ADHD, this will have close to the same effect on your intelligence as any other substance marketed to make you temporarily smarter: marginal at best.  However, if you're suffering from a cognitive deficit due to sleep deprivation, it will reduce the extent of the deficit (with close to the same effectiveness as caffeine).
> 
> Still no long term studies: I'm a little wary due to this, since the lack of long term studies and the huge gaps in our knowledge about how this medication works and our brains add up to this: "we don't really know how or why, but modafinil has x positive effects; in the decade or so it's really been around, we haven't seen any negative effects other than y; if things go really badly in the future, we'll let you know."
> 
> I view it as an occasionally useful substitute for coffee, especially if I'm so tired that the doses of caffeine I take will come with the usual negative side-effects.



That is the best short summary on this topic I've seen so far. *Heuristic* brings it down to a couple of lines.

- _Murphy_


----------



## ebola?

One issue: I don't agree with H that people tend to respond to stimulants markedly differently depending on whether they have AD(H)D or not.  Due to modafinil's unique mechanism of action, there might be some clearer difference.

ebola


----------



## P A

> @PA can you elaborate?



On a purely anecdotal basis, and at low-ish dosages that can't significantly occupy the catecholamine transporters, Provigil appears to be a decent potentiator of the so-called 'CNS stimulation' and euphoria subjectively perceived while under the influence of the better-known amphetamine and methylphenidate. [at least in my friends' experience(s); I have yet to try the cocktail myself]


----------



## PsychedelicPeptide

IMO Adrafinil is a pretty damn good product given its availability.  I cannot compare to Modafinil but am happy with using Adra a few days a week.  

I don't get excessive stimulant effects and can safely combine with caffeine or other nootropics, and I do find it slightly euphoric (especially when I first took it).  It fits well with aniracetam which can help curb its ability to make one a bit erratic or prone to cursing (apparently this is the one main drawback to Moda) although after you take it a number of times I think you can get used to this effect and know to just let your mind relax.  For some I can see this being a problem though.

One important note is that if you think you have bunk Moda/Adra you can always tell because the real stuff will make your urine smell different for the day.  It should be a strong enough odor to where you notice it without having to put your head near the toilet, or at least I (with my good sense of smell) do.  

Regarding the mechanism of action the wikipedia entry has a reference to a drug screen of modafinil against a "large panel of receptors and transporters" but the reference link is blank and I have not seen this work.  But I have been looking into this subject on and off lately and there are probably multiple relevant sites of action, in addition to the two enantiomers having their own selectivity profiles.  I wonder if in most of these clinical studies do the researchers know what enantiomer they are testing?  The mixture (which modafinil is AFAIK) I suspect in most cases, especially older studies.  But this will only add to confusion as both have their own profile and could mess with the delicacy of some of these experiments rendering their results subject to improper interpretation.  ;-P



> J Pharmacol Exp Ther. 2006 Nov;319(2):561-9.
> *Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro.*
> 
> Madras BK, Xie Z, Lin Z, Jassen A, Panas H, Lynch L, Johnson R, Livni E, Spencer TJ, Bonab AA, Miller GM, Fischman AJ.
> 
> Department of Psychiatry, Harvard Medical School, New England Primate Research Center, 1 Pine Hill Dr., Southborough, MA 01772-9102, USA.
> 
> Abstract
> 
> 2-[(Diphenylmethyl) sulfinyl]acetamide (modafinil), prescribed principally to treat narcolepsy, is undergoing assessment for other neuropsychiatric disorders and medical conditions. The neurochemical substrates of modafinil are unresolved. We postulated that modafinil enhances wakefulness by modulating dopamine (DAT), norepinephrine (NET), or serotonin (SERT) transporter activities. In vivo, we determined DAT and NET occupancy by modafinil by positron emission tomography imaging; in vitro, we determined modafinil activity at the DAT, NET, SERT, and rhesus monkey trace amine receptor 1 (TA1). In rhesus monkey, modafinil occupancy of striatal DAT was detected by [(11)C]2beta-carbomethoxy-3beta-4-(fluorophenyl)tropane and of thalamic NET by [(11)C](S,S)-2-(alpha-(2-methoxyphenoxy)-benzyl)morpholine. In vitro, modafinil effects in DAT-human embryonic kidney (HEK), NET-HEK, and SERT-HEK cells were investigated alone or combined with the TA1 receptor. Modafinil (i.v.) occupied striatal DAT sites (5 mg/kg: 35 +/- 12%, n = 4; 8 mg/kg: 54 +/- 3%, n = 3). In thalamus, modafinil occupied NET sites (5 mg/kg: 16 +/- 7.8%, n = 6; 8 mg/kg: 44 +/- 12%; n = 2). In vitro, modafinil inhibited [(3)H]dopamine (IC(50) = 6.4 microM), [(3)H]norepinephrine (IC(50) = 35.6 microM), and [(3)H]serotonin (IC(50) > 500 microM) transport via the human DAT, NET, and SERT. Modafinil did not activate the TA1 receptor in TA1-HEK cells, but it augmented a monoamine transporter-dependent enhancement of phenethylamine activation of TA1 in TA1-DAT and TA1-NET cells, but not in TA1-SERT cells. The present data provide compelling evidence that modafinil occupies the DAT and NET in living brain of rhesus monkeys and raise the possibility that modafinil affects wakefulness by interacting with catecholamine transporters in brain.





> Synapse. 2009 Aug;63(8):698-704.
> *Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.*
> 
> Seeman P, Guan HC, Hirbec H.
> 
> Department of Pharmacology, Medical Science Building, University of Toronto, Toronto, Ontario, Canada.
> 
> Abstract
> 
> Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.





> JAMA.  2009 Mar 18;301(11):1148-54.
> *Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications.*
> 
> Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, Wang GJ, Jayne M, Hooker JM, Wong C, Hubbard B, Carter P, Warner D, King P, Shea C, Xu Y, Muench L, Apelskog-Torres K.
> 
> National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
> 
> Abstract
> 
> CONTEXT: Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. OBJECTIVE: To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. DESIGN, SETTING, AND PARTICIPANTS: Positron emission tomography with [(11)C]raclopride (D(2)/D(3) radioligand sensitive to changes in endogenous dopamine) and [(11)C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007-2008) at Brookhaven National Laboratory. MAIN OUTCOME MEASURES: Primary outcomes were changes in dopamine D(2)/D(3) receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. RESULTS: Modafinil decreased mean (SD) [(11)C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P = .02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P = .002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P = .02), reflecting increases in extracellular dopamine. Modafinil also decreased [(11)C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P < .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P < .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P = .001), reflecting occupancy of dopamine transporters. CONCLUSIONS: In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.



A follow-up to their last statement...

The lack of modafinil abuse also highlights the need for heightened awareness for an increased understanding of how different molecules can stimulate the same systems but produce significantly different results.  =)


----------



## P A

D2High occupancy isn't particularly relevant to healthy humans in vivo, as evidenced by the apparent lack of D2 agonist-associated [side]effects during the clinical trials. Rule of thumb: if none of the patients are vomiting, twitching, or hallucinating, it's probably not a functional D2 agonist, the hallucinations being particularly relevant in disorders like schizophrenia, which, interestingly enough, Provigil is being used to treat. And the facts that the molecule happens to both inhibit reuptake and weakly displace cocaine at the transporter don't predicate lumping modafinil's mechanism in with the rest of the classical pyshcostimulants as though the real-world clinical profile has lost relevance. None of the mechanisms described above do anything to explain modafinil's more selective behavioral properties and negligible incidence of side effects as compared to other contemporary catecholamine transporter blockers and substrates. 

Directly increasing conductance across the membrane or amplifying presynaptic Na/Ca influx (by way of some of the mechanisms I mentioned in my other post) could theoretically allow for elevated displacement of transporter ligands and transient, voltage-dependent inhibition of monoamine reuptake (and stimulation of electrically evoked release) resembling that of the conventional stimulants, minus the stereotypy, euphoria, and locomotor effects. This theoretical RI/release mechanism would be similar to that of acetylcarnitine (which modestly releases dopamine and acetylcholine through selective nicotinic modulation/agonism) and hyperforin (broad-spectrum reuptake inhibition via presynaptic TRP6 activation on GABA, glutamate, 5-HT, DA, and NE neurons) on their target neurotransmitter systems. Regionally selective exocytosis of GABA neuron gap junctions would allow for enhanced H3 receptor binding alongside some of the low-level 'amphetamine-like' effects observed in higher doses.

On the other hand, modafinil could simply be exploiting an as-yet undiscovered chemical discrepancy, either by binding exclusively to an allosteric site on the transporter or acting on a regionally localized subunit. But I doubt it, if only because the "enhanced coupling" theory seems _much _ more promising as a novel explanation for novel drug properties.


----------



## Heuristic

ebola? said:


> One issue: I don't agree with H that people tend to respond to stimulants markedly differently depending on whether they have AD(H)D or not.  Due to modafinil's unique mechanism of action, there might be some clearer difference.
> 
> ebola



Well, and I apologize for not including references in here, most of what I've read concerning cognitive enhancers has found, as one would expect, much more dramatic differences for people who have ADD/ADHD than for normal subjects.  That is, improvement after dose for people with ADD/ADHD is much more dramatic than improvement after dose for normal subjects.

For people with high IQs and not suffering from ADD/ADHD, the effect of these medications was especially small.

Not really all that surprising, is it?  My only caveat would be that these medications are effective at restoring a substantial amount of function lost due to sleep deprivation.

I also have the sense here that I've misunderstood part of what you're saying.  Could you elaborate?


----------



## PsychedelicPeptide

Well the important thing for the D2 paper that I saw is the large discrepancy between the two modafinil isomers, where the R form has activity but S virtually nothing.  BUT their data is a bit suspicious since they say so many compounds stimulate D2... I didn't read the article but looking back again on it I'm not sure we should buy it.  You are right about the D2 agonism though I wasn't thinking much about that.


----------



## naginnudej

Does anyone know what the rectal bioavailability of this substance is?


----------



## Solipsis

No but I bet its high, considering the effectiveness of insufflation.

Actually, watch out not to overshoot your target dose because that could be quite uncomfortable.
Intranasal an impressively small dose gets absorbed not only well but hard and fast, letting you easily
achieve the desired effect.
Yes it lasts a little less long but not thát much, plus you could always redose. I like to be able to sleep
without problems after using though. Not that its extremely hard to fall asleep a while after dosing...

So, do you think it undergoes significant first-pass metabolism?


----------



## Silverfox

Solipsis said:


> Intranasal an impressively small dose gets absorbed not only well but hard and fast, letting you easily
> achieve the desired effect.



What dose do you insufflate and are you insufflating ground up tablets? My 200mg Modalert tablets weigh 320mg so the effective dose is 62.5%


----------



## MurphyClox

At this point I _have_ to chime in...
Why are you guys snorting modafinil at all? There is no rush of upcoming effects, not even when injecting the drug AFAIK. Bioavailalibity seems to be sufficient. So why the heck putting such stress to your nose mucosa?

Please enlighten me. Thx!


- _Murphy_


----------



## naginnudej

MurphyClox said:


> At this point I _have_ to chime in...
> Why are you guys snorting modafinil at all? There is no rush of upcoming effects, not even when injecting the drug AFAIK. Bioavailalibity seems to be sufficient. So why the heck putting such stress to your nose mucosa?
> 
> Please enlighten me. Thx!





Solipsis said:


> No but I bet its high, considering the effectiveness of insufflation.





> Intranasal an impressively small dose gets absorbed not only well but hard and fast, letting you easily
> achieve the desired effect.


There seems to be some merit In Sols post.



> So, do you think it undergoes significant first-pass metabolism?



This may not be of much help, but I read these pending patents which [briefly] discuss the matter. Their credibility is for you to decide:



> [0028]As noted above, currently available compositions of modafinil are in the form of tablets that are swallowed. Accordingly, modafinil may be formulated for oral administration for hepatic first-pass metabolism wherein the drug is swallowed and passes into the gastrointestinal tract (gut) and then into the liver before entering the systemic circulation. However, preferred routes of administration of modafinil for compositions and methods described herein are those that are likely to provide faster delivery and lower risk of degradation of modafinil than are associated with first-pass metabolism. Such preferred routes of administration of modafinil include, but are not limited to, sublingual, buccal, nasal, intravenous, subcutaneous, intramuscular, topical (including transdermal), and rectal modes of administration. Although delivery directly into the systemic circulation is more preferred than via the gut and liver (hepatic first-pass metabolism), the concentration of modafinil in the systemic circulation must be sufficient to ensure that an effective amount penetrates the blood-brain barrier and is delivered to the brain and CNS, which are the preferred targets of delivery. Administration to the mucosa of the nasal passages or of the mouth is particularly preferred owing to the fact that some of the capillaries underlying the mucosa provide a conduit directly to the circulation of the brain and CNS. Thus, formulations of modafinil for nasal or oral mucosal administration are not only convenient for pm dosing, but may provide the added benefit of requiring a lower concentration per dose owing to the enhanced efficiency of delivery to the brain and CNS.
> 
> Read more: http://www.faqs.org/patents/app/20090318559#ixzz0w39VjAbn


----------



## ebola?

> Well, and I apologize for not including references in here, most of what I've read concerning cognitive enhancers has found, as one would expect, much more dramatic differences for people who have ADD/ADHD than for normal subjects. That is, improvement after dose for people with ADD/ADHD is much more dramatic than improvement after dose for normal subjects.



I don't think that casual conversation demands references.  On second thought, I don't think that we actually disagreed.  The cognitive effects of stimulants, namely increased top-down directed linear thought, and according reduced influence of bottom-up novelty on top-down directives, tend to be similar between patients with ADD and without.  However, in intelligence tests and perhaps scholastic work, those with problems with distractability benefit more in terms of test-performance from this effect.

So what I meant (expressing it poorly) is that seeming paradoxical effects of stimulants (eg, calming, drowsiness) aren't actually THAT much more common among those with ADD than others.  



> For people with high IQs and not suffering from ADD/ADHD, the effect of these medications was especially small.



Mmmm...perhaps pedantically, there's a logical problem with sorting our subject groups by IQ but also using IQ tests as our dependent measure.  Eg, those with high IQs benefit little from stimulants 'cause they already possess whatever characteristics are useful for scoring high on IQ tests.  Speculating, though, such individuals might be more top-down cognitively directed and motivated to begin with.

ebola


----------



## IHateOpiophobes

Snowbear said:


> The doctors who prescribed it both said it took time also.  I think the manufacturer's reps stretch that point to doctors to make it sound like an "anti-depressant".  I think the info that came with the package said the same thing.



My doctor takes the stuff himself on occassions and he made it sound like speed except he had never done speed....so I dont think he realized.  I noticed the effects the first time.  Its just so subtle.  Which I think I love about the drug...is there is no harsh side effects.  No real ups or downs.

The package says nothing about that.


----------



## IHateOpiophobes

Its like what codeine is to oxycodone.....nuvigil is to dextromethylamphetamine.  (NASTY METH)

IMO


----------



## Solipsis

I don't insufflate crushed tablets,  it's pure powder. Additionally it causes the least irritation to the nasal mucosa of pretty much any compound that's been up there.

The modafinil is bumped but I don't weigh it because the amount of material that fits on the tip of a little metal lab spatula used to bump is effective and very fast at that. So that is my ´unit´ for a dose amount. One or two repeats may make the effect much more prominent but 1 or 2 are enough to get the eyes wide open. Very much the wakefulness promotion rather than stimulation.
I bet the amount of a bump is 10-25 mg, that is definitely a significant difference with oral doses of 200 mg a tablet!

Mild palpitations and signs that I have taken more than enough was noticed after about 8-10+ bump but it was absolutely not alarming at any point, that points to a good therapeutic index overdose-wise although I am not making any toxicity claims.


----------



## Epsilon Alpha

I don't speak Russian(?) but I love the bump!
If I recall correctly one of the main MOA uncovered currently:
- Alpha1 agonist
- D2 agonist
- DAT inhibitor (closing it in a novel formation)
- Modulates gap junctions via a Ca++ dependent enzyme


----------



## laCster

ok snorting nuvigil is not cool, it gave me the worst nasal irritation of my life, it fucking sucked..


idk i mainly use modafinil as a 3A4 inducer to boost the amount of norbup converted from bup... 

but bump on this thread


i also agree that nuvigil (modafinil) goes well with amphetamines.  i took roughly 75mgs nuvigil with 15mgs Adderall and it felt like 20-30mgs addyt


----------



## Hammilton

I did not know about the bup to norbup conversion.  I'll have to look into that.  I take 150mg of Nuvigil daily.  It's a wonderdrug, imho.  Absolutely zero side effects and lots of positives!  No compulsion to take or to take more, either.


----------



## amanitadine

Ham, I trust your take more than most, even when it comes to subjective effects, as it is clear you still keep your discerning mind. So, your phrase "wonder drug" caught my eye (heavy words!).  I've never tried nuvigil, just modalert years ago, in all sorts of doses, with basically no effect other than what I assumed was placebo. Is nuvigil that much better, more than just 2x as strong, or is there something negative going on in the "inactive" isomer of modafanil? Or is this individual just not susceptible to these mild effects? Still got my curiosity here. . . .


----------



## AlphaMethylPhenyl

Hammilton said:


> I did not know about the bup to norbup conversion.  I'll have to look into that.  I take 150mg of Nuvigil daily.  It's a wonderdrug, imho.  Absolutely zero side effects and lots of positives!  No compulsion to take or to take more, either.



What else do you take? The effects your experiencing are probably somewhat contingent on any other drug you regularly ingest.


----------



## MeDieViL

> Eg, those with high IQs benefit little from stimulants 'cause they already possess whatever characteristics are useful for scoring high on IQ tests.


Focus, speed of thinking and productivity are not related to IQ but improved by stimulants so i disagree with this statement.



> the hallucinations being particularly relevant in disorders like schizophrenia, which, interestingly enough, Provigil is being used to treat.


It improves the conditions negative symptions in combo with a ap wich shire has shown to do succesfully with amphetamine too.



> At this point I have to chime in...
> Why are you guys snorting modafinil at all? There is no rush of upcoming effects, not even when injecting the drug AFAIK. Bioavailalibity seems to be sufficient. So why the heck putting such stress to your nose mucosa?
> 
> Please enlighten me. Thx!
> 
> 
> - Murphy


Improving bioavailability is the latest trend here, im not really a trendfollower and just take more of things.


----------



## Hammilton

> Focus, speed of thinking and productivity are not related to IQ but improved by stimulants so i disagree with this statement.



Speed of thinking is definitely related to IQ.  Much of IQ testing is timed, and the more rapidly you can process your thoughts, the higher your score will be.

I don't know about productivity, but focus and speed of thinking will both be deeply beneficial in taking an IQ test, just like with any test.


----------



## laCster

Hammilton said:


> I did not know about the bup to norbup conversion.  I'll have to look into that.  I take 150mg of Nuvigil daily.  It's a wonderdrug, imho.  Absolutely zero side effects and lots of positives!  No compulsion to take or to take more, either.




yah, buprenorphine is metabolized into norbuprenorphine (full-agonist to mu receptors) through cytochrome 450 3A4.  modafinil is a potent inducer of 3A4, and so when i take the too together, i get a foreign sensation, i feel good, my body feels sleepy and stoned, and my eyes feel heavy and are pinned. the feeling is a little subtle, but i can definitely tell when there is more norbup on my receptors than bup because the effects feel different.  usually i take 150mg nuvigil with .5-1mg suboxone in the morning, and after about 4-5 hours, i start to feel more talkative than usual, my anxiety, decreases, and i crave nicotine..

if anyone has similar effects please post!! i mean tagamet definitely does it's job well and i can really tell if i have taken cimitidine to potentiate a benzo or opiate, so shouldnt the opposite of inhibiting 3A4 accurate aswell? if tagamet noticeably increases duration and potency by inhibiting enyzmes including 3A4, then shouldnt modifinil noticeably increase th effects of norbup? i think so, but i don't have any study or grounds to go on/...

please post if you have experiences with using modafinil as a 3A4 inducer


i like modafinil too, it has very little side effects besides the fucking headaches i get sometimes.  modafinil does it's job as being a wake-fullness promoter, and helps with focus and motivation to do work.  it is very handy when i have not had alot sleep because after i take modafinil, i feel like i had 8hrs of sleep and good to go. however, it does take a while to kick in IMO, so i like amphetamines better. i think amps are all around better, but if i just need to wake up modafinil is awesome.  nuvigil's best ability is to wake you up IME and this can be very handy when studying for finals, working late, driving long distances, the list goes on and on.  also modafinil doesnt have much euphoria which is a plus for actually studying because on amphetamines i get euphoric and sometimes i am distracted by this...


----------



## Hammilton

Well, norbupe doesn't penetrate the BBB as easily and isn't as potent.  Were this metabolism occurring inside the brain, it'd be good, but as it's metabolized the liver, I'm not sure everyone will want this effect.

Additionally, buprenorphine is VERY poorly absorbed when swallowed because it's rapidly metabolized, iirc.  Is it being converted to norbupe when used orally?  If that's what's happening there, I definitely wouldn't suggest using modafinil while on Suboxone unless you wanna waste your dose.  I haven't noticed feeling sick or anything, and I just take 2mg once daily.

However, I noticed that when my doc does his drug tests, they send back their report on how much of each of maybe 20 different drugs were found.  They're all 0 of course, except buprenorphine and norbuprenorphine.  I think on Monday I'll call them up and ask if the norbupe level has increased since I went on modafinil.  I think I've only had two tests while taking armodafinil, though, so it may not be really useful, but if there's a huge change it should be apparent.


----------



## Dysphoric

I just recently scheduled myself an appointment to get some Modafinil. 

Anyways, does anyone notice a lift in mood? When's the latest one should take it? Any annoying side-effects? 100mgs or 200mgs? 

I'm asking anyone who is taking it currently or has extensive experience with it. Feel free to mention anything else about it. I'm kind of excited to find something that might help me!


----------



## Thorns Have Roses

Dysphoric said:


> I just recently scheduled myself an appointment to get some Modafinil.
> 
> Anyways, does anyone notice a lift in mood? When's the latest one should take it? Any annoying side-effects? 100mgs or 200mgs?
> 
> I'm asking anyone who is taking it currently or has extensive experience with it. Feel free to mention anything else about it. I'm kind of excited to find something that might help me!



Check out Australian Drug Discussion's modafinil discussion thread, or ask in BDD where these queries would be appropriate.


----------



## Hammilton

I notice no mood lift.  I take 150mg of R-modafinil per day, between 2:30 and 3pm, and have no problem sleeping by 1am.  I could snort a line of amphetamine at midnight and sleep by two, though..

I don't have any side effects.  Maybe slightly more headaches, and I have been losing my voice a lot lately, but I've had about three colds in the last month (terrible luck).  I blame it on my kids.


----------



## Dysphoric

Hammilton said:


> I notice no mood lift.  I take 150mg of R-modafinil per day, between 2:30 and 3pm, and have no problem sleeping by 1am.  I could snort a line of amphetamine at midnight and sleep by two, though..
> 
> I don't have any side effects.  Maybe slightly more headaches, and I have been losing my voice a lot lately, but I've had about three colds in the last month (terrible luck).  I blame it on my kids.



Yeah, it seems that the mood brightening effects are a hit or miss, varying from person to person. Does it really last for 9+ hours? 

Anyways thanks for the reply.


----------



## irobeth

Hammilton said:


> I notice no mood lift.  I take 150mg of R-modafinil per day, between 2:30 and 3pm, and have no problem sleeping by 1am.  I could snort a line of amphetamine at midnight and sleep by two, though..
> 
> I don't have any side effects.  Maybe slightly more headaches, and I have been losing my voice a lot lately, but I've had about three colds in the last month (terrible luck).  I blame it on my kids.



No explicit lift in mood here, but it definitely enables a switch to mania

Headaches, no; nausea, depends on some unknown

I'm noticing diminishing returns lately, and I'm worse at ignoring physical fatigue than before.

No compulsion to redose, no inhibition not to; sleep is fine when I do, but I am 28-hour so I can't reliably judge this.


----------



## magniloquentcunt

has anyone tried it as a cure for anhedonia/depersonalization/lethargy as a consequence of SSRI?


----------



## AlphaMethylPhenyl

no but I am looking into that too

Nootropics might be more of a help for you


----------



## magniloquentcunt

Ho-Chi-Minh said:


> no but I am looking into that too
> 
> Nootropics might be more of a help for you



what for example? the only one i can get at the pharmacy is piracetam, and it looks like the most "vague" option


----------



## Solipsis

Piracetam is not really vague, it is the original nootropic drug (not counting ancient tonics like Bacopa) but just not quite as potent as newer ones.

Read up here:
*Nootropics thread V1*
*Nootropics thread V2*

Personally I don't find that modafinil has that much potential as a nootropic, for me it is purely a wakefulness promotor. I seem to take it via an unusual RoA though apparently (intranasally), I am not sure how significant first-pass metabolism is with it.

Back to moda then...


----------



## nuke

After going through about 300g of this drug I have some comments:
1) There is strong cross tolerance with amphetamine or methylphenidate.  10mg PO of methylphenidate had no effect after using modafinil for two weeks straight and being totally methylphenidate naive for two months.  10mg normally turns me into a calculus crunching machine.
2) It's really good if you haven't slept, but it seems to make me aggressive, even a little more so than classical stimulants.
3) It also induces more panic attacks than AMP/methylphenidate, particularly at high doses.
4) A weird side effect I get is vertigo; I never get this on any other stimulants.



Dysphoric said:


> Yeah, it seems that the mood brightening effects are a hit or miss, varying from person to person. Does it really last for 9+ hours?
> 
> Anyways thanks for the reply.


Duration for me is 10-14 hours.  Ideal dose 75-150mg.


----------



## TCMVegas

Nuke, I have "ADD" in the sense that I have a hard time motivating myself to work at the level that I need to in my college classes. I never start large homework assignments until like 9pm the night before, which just doesn't work anymore at this point in my academics. I think I'd prefer stimulants over SSRIs or bupropion (which I've tried). Instead of perpetual NDRI activity, I want it to be working just while it's useful to me, not when I'm screwing around and not working.

In the past I took 40+mg of amphetamines every weekday, and that turned out disastrous. I basically unwillingly abused amphetamines because of imminent deadlines during the week, then crashed hard on the weekends. I had terrible work habits, and terrible sleeping habits as well due to amphetamines. I want to adopt healthier habits, in terms of both studying and sleeping. 

I'm currently considering IR methylphenidate twice a day for studying, so that I'll get 3-4 hour study sessions, once before and once after daily classes. This is my plan because with amphetamines' half-life, unnecessary receptor downregulation occurs while not making effective use of the drug's very long duration. I'd rather try to keep a low tolerance and use the full duration of effects.

Do you think that modafinil, or methylphenidate, or a combination would be best for daily use in school? I have personally never noticed memory issues due to stimulants.


----------



## polarbearsarecool

Apparently the reason of the difference in Modafinil/Provigil/Nuvigil VS MODALERT/other generic overseas brands is because of the difference in recrystallization solvent from the final product. Apparently modafinil can form some odd crystalline structures?

http://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=2002043207&KC=&FT=E&locale=en_EP


----------



## Hammilton

I dunno about that, but the difference between Modafinil/Provigil and Nuvigil is an issue of racemic vs. enantiopure.

I dunno why crystalline structure would be relevant.  It is true that modafinil can form a number of different crystal structures, but the powder (>90%) is milled down to under 200 microns.  That's pretty itty bitty.  The form used for Nuvigil is actually stated on the PI sheet to be the least soluble form.  That's for the name brand.  The problem with Modalert and the other generics cannot be the crystal forms they use, as the least soluble is already used by the brand...

Just my thinking.



> 1) There is strong cross tolerance with amphetamine or methylphenidate. 10mg PO of methylphenidate had no effect after using modafinil for two weeks straight and being totally methylphenidate naive for two months. 10mg normally turns me into a calculus crunching machine.
> 2) It's really good if you haven't slept, but it seems to make me aggressive, even a little more so than classical stimulants.
> 3) It also induces more panic attacks than AMP/methylphenidate, particularly at high doses.
> 4) A weird side effect I get is vertigo; I never get this on any other stimulants.



On point number 1, I don't know if I completely agree.  There may be strong cross-tolerance with methylphenidate- I noticed that 20mg dexmethylphenidate was barely noticeable, and I'm pretty sensitive to stimulants.  However, a day or two later a 40mg Vyvanse was noticeably strong.  However, there was no euphoria.  It was simply a useful, focused stimulation.  15mg Adderall XR was noticeable, but weak one day, the next day completely unnoticed.  That's probably more a dosing thing, though.

2-  Absolutely, that's definitely where it shines, and really, where it was meant to.  I've been getting five to six hours of sleep this week, and it's been excellent at 150mg.  I don't notice any aggression.  I have about 20, 25 people I have to tell what to do and a lot of shit to keep in order on my job, so I need to constantly be assertive, but I've never crossed into aggressive, I don't think.  There have been a few occasions lately where I've nearly screamed at someone (I was yelling pretty good) because they seriously fucked something up, but I don't think it was more than usual, or uncalled for.  Two really serious fuck ups in 20 minutes, one while fixing the first- when I told him that he needed to move something or it'd get damaged, two minutes later he apparently forgot, and lo and behold, fucked it up good.

3- I have never experienced any panic attack while on the drug.  I do notice that even at 150mg, if I have any caffeine early (before about 6 hours post-dose) I get really jittery and anxious feeling.

4- I've not had serious vertigo, but there have been times when I've been walking someone in a bit of a hurry and all of a sudden I'll notice that my head feels like it's spinning, and I've gotta close my eyes for a second and let it pass.



75 to 150mg?  You mean for Armodafinil/Nuvigil, right?  For modafinil that'd be real low, no?  That's roughly 37.5-75mg of R-modafinil.  Do you experience effects from that dose?  I've always been at 150mg, I  think maybe I took half of one my first dose, I don't recall.


----------



## polarbearsarecool

Hammilton said:


> I dunno about that, but the difference between Modafinil/Provigil and Nuvigil is an issue of racemic vs. enantiopure.
> 
> I dunno why crystalline structure would be relevant.  It is true that modafinil can form a number of different crystal structures, but the powder (>90%) is milled down to under 200 microns.  That's pretty itty bitty.  The form used for Nuvigil is actually stated on the PI sheet to be the least soluble form.  That's for the name brand.  The problem with Modalert and the other generics cannot be the crystal forms they use, as the least soluble is already used by the brand...
> 
> Just my thinking.
> 
> .



Obviously provigil/modafinil vs Nuvigil is stereo differences but I'm saying the difference between the Cephalon brands vs the generic overseas- Modalert etc is definitely due to crystalline structure.

I can tell you crystalline structure and solubility is CRUCIAL for various drugs, hell look at an excerpt from wikipedia

"Solubility (metastable) also depends on the physical size of the crystal or droplet of solute (or, strictly speaking, on the specific or molar surface area of the solute). For quantification, see the equation in the article on solubility equilibrium. For highly defective crystals, solubility may increase with the increasing degree of disorder. Both of these effects occur because of the dependence of solubility constant on the Gibbs energy of the crystal. The last two effects, although often difficult to measure, are of practical importance.[citation needed] For example, they provide the driving force for precipitate aging (the crystal size spontaneously increasing with time)."

Now whether Cephalon intended on crystalline forms at first, they seem to have realized that this affects the solubility in that it increases it and the dissolution thereof, or decreases it. Via this decrease metabolic interactions may decrease as well due to it not dissolving as well in stomach acid/water. (Nuvigil is blatantly seen to be highly insoluble in water- while modalert will easily dissolve).

The least soluble for modalert is clearly not being used because that depends on the recrystallization solvent, if the least soluble was being used- the "ideal" modafinil would be out there- but modalert dissolves and nuvigil does not. 

All because of my guess- Indian chem companies are saving money on the recrystallization solvent by not using the same that cephalon uses, they obviously must know this- it still produces modafinil but a version that is wayyy more soluble, is metabolized quicker(via dissolving easily), causes more enzymatic induction(via dissolving easily), and is probably a higher percent of the sulfone(produced when the reaction goes too long, or in too large batches). 

Sunpharma's reaction methods may ever favor l-modafinil, or hell l-modafinil may actually dissolve more readily via purification, or in vivo in this crystal type, than R-modafinil will (either loss during purification or poor solubility in vivo because of its crystal form) and thus low activity. The inverse could be true if you think the more expensive(possibly in a patent somewhere) recrystallization solvent dissolves l-modafinil poorly, and R-modafinil wayyyy higher(thus cephalon may not ever use a stereoselective synthesis and eliminate L-modafinil via purification step) thus creating a more efficient crystalline form-that is poorly soluble and is a metabolic god.

I have the papers ill find the solvents used by both but this could be it, its big pharma, theres obviously something hiding.


----------



## polarbearsarecool

www.intechopen.com/download/pdf/30914

2nd page

2. Impact of crystal habit on pharmaceutical processing
Drug discovery and characterization relies on the nature of the target molecule and the
relative physicochemical properties of drugs. Identifying all relevant crystal habit of a drug
which is an important variable in pharmaceutical manufacturing at the development phase
from research to commercialization is of substantial value. Due to the different crystal form
variations of some basic physical properties like, solubility, dissolution rate, melting
behavior, and certain micromeritic properties or performance characteristics, e.g. tablet
compressibility, mechanical strength, powder flow provide alternatives to select a form that
presents the suitable balance of critical properties for development into the drug product.
Establishing such modification information at an early stage of drug development process
lessens the risk of process alterations given form changes and brings in the opportunity to
attain more comprehensive rational property coverage.
The merit of changes in crystal surface form and habit of drug powders by recrystallization
method is much more realized when there is an essential to diminish variations in raw
material characteristics, to certify reproducibility of results during drug preformulation, and
also to judge fairly about the cause of poor performance of a dosage form. Besides, the
changes in crystal habit of a drug going together with or without polymorphic
transformation at some point in processing storage could account for serious implications of
physical stability in dosage forms. Thus, it seems underlying to have a deeper insight to the
crystal structures and control the solid-state chemistry of drug substances to design a more
systematic and intellectual pharmaceutical dosage forms.
In a survey carried out by Sinclair et al. ibipinabant a potent and highly selective
cannabinoid receptor antagonist was evaluated for its solid-state physical stability and
recrystallization kinetics in tablet dosage forms using fourier transform raman spectroscopy.
The findings of the study showed that exposure to moisture had notable influence on the
crystallinity of amorphous ibipinabant. The recrystallization kinetics measurements
revealed a two-step process with an induction period (nucleation) followed by rod-like
crystal growth by application of the Johnson–Mehl–Avrami kinetic model. On the whole
their method provided reliable and highly accurate predictive crystallinity assessments after
exposure to a variety of stability storage conditions for ibipinabant (Sinclair et al., 2011).
Recently, Dahlberg et al. analyzed the stability of the amorphous drug, flutamide, by a
combination of localized nuclear magnetic resonance (NMR) spectroscopic and NMR
imaging techniques. Owing to the fact that, NMR relaxation is sensitive to both the
crystalline and amorphous state and the size of the drug substance, it allows for an in situ
monitoring of the state of the drug during tablet disintegration and dissolution periods.
With regard to the results of the NMR experiments, recrystallization was believed to be
related to its enabling factors such as local hydration level and local mobility of the polymer
matrix. Eventually, it was verified that the primarily amorphous flutamide may recrystallize
either by nanoparticle coalescence or by ripening of crystalline particles (Dahlberg et al.,
2011).
The solid-state properties of sulfathiazole and chlorpropamide were modified through
recrystallization using supercritical antisolvent process by Yeo et al. They confirmed that the
operating conditions of the system such as carbon dioxide injection rate, type of solvent, and
temperature significantly had an effect on the physical characteristics of the resulting
crystals. Considering the results of the study, drug crystals processed with supercritical
system exhibited more ordered appearances with clean surfaces and sharp angles compared
with the unprocessed particles where crystal habit changed from tabular to acicular when
the carbon dioxide injection rate increased. Photomicrographs of sulfathiazole crystals with
methanol as a solvent, confirmed a needle-like acicular and a tabular crystal habits in rapid
and slow injections, respectively. Whereas, in the case of chlorpropamide, processed drug
particles in the rapid injection experiment exhibited columnar habit in a regular shape,
while relatively large crystals with sharp angles were observed in the slow injection mode
when acetone was used as the solvent. Overall experimental observations suggested that the
supercritical antisolvent process could provide favorable environment for the solid growth
of a single type of crystalline drug, minimizing the conditions for growth-related
imperfections (Yeo et al., 2003).
According to the fact that thermal analysis has been frequently used to identify crystal forms
of drugs and in the course of thermal analysis, crystal transformation is often observed as
well as melting and decomposition, Suzuki et al. studied mechanisms of thermal crystal
transformation through melting and recrystallization. They characterized two anhydrates
(&#56256;&#56770;-from and &#56256;&#56771;-from) and two hydrates (hemihydrate and monohydrate) forms of a novel
fluoroquinolone antibiotic, sitafloxacin, in addition to sesquihydrate which is used in the
marketed drug products. The results of crystal structural that were characterized by infrared
spectroscopy, X-ray powder diffractometry and thermal analysis revealed quinolone rings
of sitafloxacin had distorted planar structure and quinolone ring of the drug in &#56256;&#56770;-form and
monohydrate hold opposite torsion to those in &#56256;&#56771;-form and sesquihydrate. These kinds of
thermal analysis are often recommended as a routine tool for quality control of thermal
dehydration and subsequent crystal conversion of drugs (Suzuki et al., 2010).
.....

NOTE: THE LAWSUIT vs TEVA incorporates discussion of the crystal type of nuvigil and the recrystallization solvent of choice- scroll to the bottom of the pdf

patentdocs.typepad.com/files/nuvigilorder.pdf

Teva agrees to cooperate in good faith to provide for use in the Litigation, or any action related thereto, reasonable discovery sufficient to show the following:
1.
The identity and properties ofall armodafinil solid forms prepared or studied by or for Teva, including, but not limited to, the polymorphic and solvate forms disclosed in any Cephalon or Teva U.S. or foreign patent or patent application, and the reasons why any research or development by or on behalf of Teva related thereto is or is not ongoing.
2.
The reasons underlying, and bases for, Teva's decision to use the Form I polymorph of armodafinil ("Form I") in its proposed generic armodafinil products under ANDA 200-152, including any analyses conducted by or for Teva relating to the stability or other properties of Form I or comparing Form I with other armodafinil solid forms.
3.
Any disadvantages ofthe armodafinil synthesis or crystallization procedures disclosed in U.S. Patent No. 4,927,855 known to Teva, and the bases therefor, including, but not
Case 1:09-cv-00918-GMS Document 119 Filed 05/11/11 Page 4 of 5 PageID #: 1106
limited to, the basis for Teva's statements in Patent Application Publication No. 2008/0031939 at ~~ 8, 10, 14,36, and alternative methods for making armodafinil developed by or for Teva and the reasons underlying, and bases for, Teva's development of the alternative methodes).
4. The identity and crystal structure measurement of all armodafinil polymorphs obtained by or for Teva when using ethanol (regardless of concentration or grade or purity) as a crystallization solvent.
2
Case 1:09-cv-00918-GMS Document 119 Filed 05/11/11 Page 5 of 5 PageID #: 1107


As you can see this is a stipulation that makes TEVA prove their methodology and their own studies that found the ideal  usage of the crystal type, the recrystallization solvent-*ethanol-
* as a means to kind of halt them( ex fake data, their lead on  this solvent/crystal type could be proved that it came from a cephalon leakage and not their own clinical data, if there is no data or trials of the other types them cephalon wins, but most likely TEVA has covered themselves.)

Now in comparison-MODALERT...
Looking at SUNPHARMA'S patent for modafinil and their derivatives..

http://www.sumobrain.com/patents/wi...lmethylsulfinyl-derivatives/WO2005046854.html

we can see on page 17 where it references its substituents, modafinil is shown as example 1 ( where r1=h) and on page 18...
"The above product is charged in acetone and heated to 50-55 C. DM water is added to the reaction mixture ...... The precipitated product is filtered and washed with acetone water mixture to furnish compound of formula 1 (wherein R1=H)..."(MODAFINIL)
There are 3 other methods but they also incorporate DI water and the last incorporating methanol, notably these are not recrystallization but complex purification technique(which affects crystal formation via solvent used)

So most likely we can conclude absolute ethanol recrystallization is skipped and this other purification technique is used for MODALERT, conflict could be completely evaded with the drug- but im sure the recrystallization/preparation of the new form of it via ethanol is a well kept patented secret. This could be how they evaded patent conflicts because of the final molecule's actually not being the same(size crystal structure). 

Apologizes for the rambling block of text but hopefully someone else will attempt this, im actually going to recrystallize a small batch of the modalerts i have in absolute ethanol and report back.. goodluck


----------



## TCMVegas

polarbearsarecool said:


> Apologizes for the rambling block of text but hopefully someone else will attempt this, im actually going to recrystallize a small batch of the modalerts i have in absolute ethanol and report back.. goodluck



Very glad to hear that!

So I guess the obvious question, which I haven't seen asked, is if a decreased bioavailability due to ModAlert's production process can be offset by simply taking more. I don't see how this would possibly _not_ work...


----------



## polarbearsarecool

TCMVegas said:


> Very glad to hear that!
> 
> So I guess the obvious question, which I haven't seen asked, is if a decreased bioavailability due to ModAlert's production process can be offset by simply taking more. I don't see how this would possibly _not_ work...



No due to this situation the crystal type can favor S isomer concentration over R
 As well as reducing duration of action etc, I've taken consistnly more modafinil doses daily to chase an effect


----------



## Nucynta_80

I've considered switching from my low dose Adderall (prescribed at 10mgs once daily) to either Provigil or Nuvigil. The main reason why? My job does random drug screenings (which equates to roughly twice a year) for illegal drugs (SAMSHA-5). Adderall shows up obviously as AMP. The wonderful people at the drug testing agency wake me up 2 days after my test to ask if I have a legit reason I tested positive for AMP (even though they have each successive drug test on record). So I have to fax over my script and then they call to tell me that they report back to the organization I work that the results were negative. I'm worried one day they won't get the prescription fax and they'll tell my organization that I failed the test.

So I've been considering Provigil or Nuvigil as a replacement, but so far from what I've read up on it, I'm not convinced its a suitable replacement for my ADHD and that it could negatively affect my sleep.


----------



## Dysphoric

Nucynta_80 said:


> The wonderful people at the drug testing agency wake me up 2 days after my test to ask if I have a legit reason I tested positive for AMP (even though they have each successive drug test on record). So I have to fax over my script and then they call to tell me that they report back to the organization I work that the results were negative. I'm worried one day they won't get the prescription fax and they'll tell my organization that I failed the test.



That's honestly a dumb reason to want to switch something that works for you. You can't get fired for having a script!


----------



## chris106

polarbearsarecool said:


> Apologizes for the rambling block of text but hopefully someone else will attempt this, im actually going to recrystallize a small batch of the modalerts i have in absolute ethanol and report back.. goodluck



Hey everyone!

First of - so sad to see this great thread stagnating 

I recently ordered Modalert online, to test if it has possitive effects for me, before I might get to test the real-brand modafinil some time soon.

I've been on MPH and then Amphetamines for the last few years, but they allways had nasty side effects. Since I suspectedly may have a sleep disorder(will be tested soon) I might get prescribed Modafinil by my doc, at least for a short test run. But the chances that german health-care will pay for it in the long run are slim to none, sadly.

Hence the modalert - I just wouldn't be able to afford the real deal for a longer period of time.

My question to you,  polarbearsarecool, and everyone else of course:

I don't know much about chemistry, but from what I get, the problem with generic modalert might be it's none-crytalized form compared to brand-name Modafinil/Provigil due to patency-issues?
How exactly would one "recrystallize" modalert, and have you had any success yet in doing so? Is there a way to add other compounds or supplements to modalert, to reach this effect, or simply make it work better? To summarize: is there a way to make it work in the way the original brand does?

Or would I need a chemistry lab to achieve that? :D

Edit: My bad, I just realized that you allready explained how you try to achieve recrystallization in the quote above. But the question remains: Did you have success and are there simpler ways?


----------



## magniloquentcunt

Open question:
Methylphenidate (Ritalin, brand) does not work for me: took up to 60mg to no avail: i feel no different, besides being a bit more chatty.
Any of you in my boat? Did Provigil work for you???


----------



## Hammilton

It is known that provigil/nuvigil stimulates the enzyme that metabolized buprenorphine to norbuprenorphine.

Based on urine screens prior to nuvigil (150mg daily) use, my norbuprenorphine level was 71ng/L.

After three months of nuvigil use, my norbupe level has risen to 170 to 199ng/L.  That is a consistent level, it the first month it was 185, the 3rd month was 199, and the second month was 172, so it doesn't seem to be exactly constant.  This is from a 2mg / day dose.

That's a pretty substantial rise.  All urine screens have been conducted with 36 hours (+/- 3.5 hours) between last suboxone and 24 (+/- 4 hours) nuvigil dose.


----------



## chris106

> After three months of nuvigil use, my norbupe level has risen to 170 to 199ng/L. That is a consistent level, it the first month it was 185, the 3rd month was 199, and the second month was 172, so it doesn't seem to be exactly constant. *This is from a 2mg / day dose*.



That part confuses me... Is it by chance a typo?

And another quick question: Does anyone here know if it's safe to combine Tramadol (ocassionaly) with noopept or other racetams?


----------



## sekio

2mg/day of suboxone, not of modafinil.


----------



## MeDieViL

chris106 said:


> That part confuses me... Is it by chance a typo?
> 
> And another quick question: Does anyone here know if it's safe to combine Tramadol (ocassionaly) with noopept or other racetams?



hmm probably but tramadol increases risk for seizures this may the the case for the racetams as they are glutaminergic in action, so titrate carefully.


----------



## polarbearsarecool

MeDieViL said:


> hmm probably but tramadol increases risk for seizures this may the the case for the racetams as they are glutaminergic in action, so titrate carefully.





yeah i did pram/oxi/nef for 6 months on trams, racetam use definitely clears things up for the opiate ridden mind somewhat and can be extremely euphoric at times(chronic tramadol usage im talking), may even increase the seizure threshhold(the opposite of trams snri nature that lowers it). But a few times i've had dangerous results, mainly combining pramiracetam, ethanol, hash oil, and higher tram doses. 

I always figured it was wierd though because taking racetams+ amphetamine for me is dysphoria and blunting of effects, i literally have to stop racetams/nuvigil within 24 hours if i want to amphetamine the next day, still its lackluster. 

Which would make us think trams+ racetams are death right? It is not however, the bad effects from amphetamine+racetams stems from their shared effects on NO, ion channels, and more.. 

Definitely go for it.


----------



## chris106

> hmm probably but tramadol increases risk for seizures this may the the case for the racetams as they are glutaminergic in action, so titrate carefully.



Thanx, and don't worry - I allways do. Will start with 50mg Trama and work my way up till 150mg one test at at time when on racetams...



> I always figured it was wierd though because taking racetams+ amphetamine for me is dysphoria and blunting of effects, i literally have to stop racetams/nuvigil within 24 hours if i want to amphetamine the next day, still its lackluster.



Interesting, was the same for me. And great information provided, thanks for that! I do however, like mentioned above, only plan on using tramadol on specific occasions and just up to 150mg of it in combination with racetams. Won't go into too much detail, but it helps  me with a certain condition occasionally, but that has nothing to do with me wanting to fight pain or trying to elevate mood - it's something else entirely.

However, I guess judging from what you said, in these boundaries I should be relatively safe with occasional 150mg Trama + racetams/ noopept. I will let you guys know once I try it (probably as soon as in the next 14 days)

One more thing: Since I will take a choline source (choline bitatrate) with the noopept,too - could that have any harmfull effect with Tramadol on itself? (I really don't see how, but don't want to take any risks...)


----------



## Hammilton

Huh, With all of the interest in drugs to increase the conversion of buprenorphine to norbupe, I"m surprised that quite literally no one has been interested in actual data on it's effect.


----------



## ebola?

I would have replied, but I figured that the world could live without me having said, "Whoa, that is very intriguing and potentially actionable case-history data that confirms theoretical supposition."  Guess it can't now... 

ebola


----------



## Hammilton

It definitely can't.

More importantly, there are two people here I know that were going to try it for this purpose, but I haven't heard back from them.

Less useful info: when using this combination, withdrawal sets in about 15 hours after the last dose, and much worse.  Where I could usually go 30 hours without noticing any withdrawal symptoms, and 48 hours before I'd start having the horrible increase in RLS symptoms, with modafinil involved, RLS and yawning and eye-watering start kicking in after that 30 hour mark.


----------



## chris106

> More importantly, there are two people here I know that were going to try it for this purpose, but I haven't heard back from them.


Well, that makes me slightly nervous, i guess... ^_^'



> Less useful info: when using this combination, withdrawal sets in about 15 hours after the last dose, and much worse. Where I could usually go 30 hours without noticing any withdrawal symptoms, and 48 hours before I'd start having the horrible increase in RLS symptoms, with modafinil involved, RLS and yawning and eye-watering start kicking in after that 30 hour mark.



I'm a litlle confused by this statement... Are you talking about noopept - withdrawal? Didn't even know that was a thing... And by RLS you mean restless-legs syndrome?
I guess since I don't plan on using this combination often it wouldn't be that big a deal, but still...

By the way: Sorry if I seem clueless sometimes, but I really don't know that much about brain-chemistry (just getting into it) plus english isn't my native tounge...

Thanx a lot for your answers though! Guess I'll still try it. Hopefully I won't be the third person you don't  hear back from... :D


----------



## Hammilton

No, I don't mean they're gone, i just haven't heard back about their trials of it.  Lol.

No, I'm talking about suboxone withdrawal kicking in at about 15 hours, about 9 hours earlier than I'd like.  About the time I go to work I start feeling it, and by the time I'm leaving, when i'm sitting doing my end-of-production paperwork, my RLS is kicking in terrible.  RLS is a common symptom of opiate withdrawal, but I always have it.  withdrawal is absolutely terrible without dopamine agonists or L-dopa for that reason.  I quit suboxone two years ago, and was off it for about 8 months.  The RLS got terrible, and before I got put on pramipexole, a doc gave me cyclobenzaprine for some reason, and I didn't sleep for over three days.  I eventually went to the ER and they gave me a couple days of Valium.  I ate that in one sitting and felt good enough until my real doc gave me the pramipexole.  That worked pretty good, but eventually he gave me a long term script for diazepam, for occasional use when the pramipexole wasn't working well enough.  Well, occasional use turned into daily use, then I started buying painkillers again, so after three months of that, I decided to go back on Suboxone.

Where I am now and will hopefully be forever.  It simplifies addiction.  Instead of constantly fighting relapse and periodically fucking up my life, I can stay on it and have zero problems, no relapses, not be late to work, always be able to pass a drug test, whatever.  I hate all these people pushing absolute sobriety on addicts.  with their talk about being chained to a drug.  It's better than being chained to impulses I can't control properly and having every day be a battle.


----------



## chris106

> No, I'm talking about suboxone withdrawal...



Obviously, should have gone a few posts back again, then that would have been clear to me. >_<'



> I hate all these people pushing absolute sobriety on addicts. with their talk about being chained to a drug. It's better than being chained to impulses I can't control properly and having every day be a battle.



Definetely with you there. Glad you found something that works for you and has no nasty side-effects!


----------



## reyqaz

I had modafinil last weekend, and monday went smooth, a little bit of withdrawal, I did it again last night. And I've done more work in one night than the entire week.


----------



## Kilfer

magniloquentcunt said:


> Open question:
> Methylphenidate (Ritalin, brand) does not work for me: took up to 60mg to no avail: i feel no different, besides being a bit more chatty.
> Any of you in my boat? Did Provigil work for you???



I take modafinil or adrafinil (as pure base) 2 weeks each month alternating with two weeks of methylphenidate. I do this to avoid building up tolerance to methylphenidate without having to go through the craving and depression phase. Success is so-so because modafinil is not as harmless as its commercial promoters claim, there is a reason why it's a schedule 4 substance in the US. Modafinil is not a 'nootropic', this term is only used to make it sound as benign as vitamins. It's a CNS stimulant and it takes its toll. Euphoria is less intense but it lasts a long time and soon you find yourself seeking it even when other stims are available. You can<t really take both at the same time because the sustained mood elevation procured by modafinil nulls the methylphenidate and amphetamine high. Which brings an interesting observation: in order to truly enjoy amphetamine high you have to be slightly depressed when you take it. The contrast in mood is part of the buzz. It's almost impossible to be depressed with modafinil active in your system, you have to wait until it wears off and even then you still hesitate between re-dosing modafinil or taking the other stim. That's called addiction so it still amounts to 'choose your poison'.


----------



## AlphaMethylPhenyl

not surprising: http://jama.jamanetwork.com/article.aspx?articleid=183580


----------



## Kilfer

Nucynta_80 said:


> So I've been considering Provigil or Nuvigil as a replacement, but so far from what I've read up on it, I'm not convinced its a suitable replacement for my ADHD and that it could negatively affect my sleep.



The reasons why modafinil is not used for ADHD appear to be more of a legal/economics nature than pharmacological. In the US even more so than in France, modafinil has invaded fields traditionally monopolized by amphetamines, methylphenidate and (more recently) buproprion: narcolepsy, chronic fatigue syndrome, gerontological neurology, military applications. Those are lucrative markets that were lost to a single substance patented to a French pharmaceutical firm. Heavy arguments for the US pharmaceutical lobby to pressure the FDA to at least keep ADD/ADHD out of Cephalon's reach for the time being. But there may be another reason... 

...with regards to sleep disturbance you raise an excellent point: the potency of modafinil as a 'wakefulness promoter' supersedes that of any other known CNS stimulant, which is why the military like it so much... and why they have to use powerful hypnotics as 'no-go pills' to counteract its effects if a mission is aborted or even after a mission is completed. USN pilots who had previously been given dextroamphetamine as 'go-pills' report that when this was switched to modafinil the Ambien dose they were given as 'no-go' had little to no effect at all even though it did work with dextro. In light of this it is not unreasonable to suggest that ADHD patients treated with modafinil would require administration of relatively strong hypnotics in order to maintain a healthy sleep schedule.


----------



## Kilfer

Ho-Chi-Minh said:


> not surprising: http://jama.jamanetwork.com/article.aspx?articleid=183580



Indeed not surprising, and strongly reminiscent of methylphenidate's therapeutic journey which was initially and for almost 25 years promoted as a mild stimulant useful in the treatment of minor depression and hypersomnia. Since it was not related to amphetamines it remained on low schedules for decades with its promoters claiming it had absolutely nothing in common with 'speed' aka amphetamines. But down on the street users knew better, and the same is happening with modafinil. It is now a controlled substance in most Western countries with the notable (and likely temporary) exception of the UK and Canada. This is mainly due to the more tedious scheduling protocol used in those countries, and a more tolerant outlook on drug usage.


----------



## pizzystrizzy

Kilfer said:


> The reasons why modafinil is not used for ADHD appear to be more of a legal/economics nature than pharmacological.



I'm not so sure -- I think psychiatrists would be happy to prescribe a drug that is not schedule II if it worked as well.  Modafinil unfortunately doesn't really fit the bill.  It certainly treats ADHD symptoms, but in terms of effect size, it isn't really much better than atomoxetine.  It doesn't really compare to the effect sizes produced by the psychostimulants.   http://www.medscape.com/viewarticle/461543

As far as regulatory matters are concerned, I think if no children had developed stevens-johnsons syndrome during the  2006 clinical trial, it probably would have been approved for ADHD.


----------



## Epsilon Alpha

pizzystrizzy said:


> I'm not so sure -- I think psychiatrists would be happy to prescribe a drug that is not schedule II if it worked as well.  Modafinil unfortunately doesn't really fit the bill.  It certainly treats ADHD symptoms, but in terms of effect size, it isn't really much better than atomoxetine.  It doesn't really compare to the effect sizes produced by the psychostimulants.   http://www.medscape.com/viewarticle/461543
> 
> As far as regulatory matters are concerned, I think if no children had developed stevens-johnsons syndrome during the  2006 clinical trial, it probably would have been approved for ADHD.



Those trials seemed really strange to me, I mean roughly 30% of the children reported rashes, and there were a couple possible cases of SJS that were not followed up for with biopsies. Also, with ~30000 off-label prescriptions in children as of 2007 and no reported cases of SJS and rashes being a rare side effect in the other populations... I'm not usually a conspiracy guy but I think there were some strings pulled to make atomoxetine the only "non-stimulant" ADHD drug on the market. Of the cases in younger individuals one had possible viral cause, one had other SJS causing medications and did not have a biopsy to confirm SJS (lamotrigine), and the last was on Zyprexa, Abilify, and Luvox (all known to have slight risks for SJS). Also, note how much is "unspecified" in the 15/M case.

http://www.fda.gov/Drugs/DrugSafety...afinilmarketedasProvigil:SeriousSkinReactions


----------



## Kilfer

pizzystrizzy said:


> I'm not so sure -- I think psychiatrists would be happy to prescribe a drug that is not schedule II if it worked as well.  Modafinil unfortunately doesn't really fit the bill.  It certainly treats ADHD symptoms, but in terms of effect size, it isn't really much better than atomoxetine.  It doesn't really compare to the effect sizes produced by the psychostimulants.   http://www.medscape.com/viewarticle/461543.



But contrary to atomoxetine modafinil is a stimulant, please refer to Ho-Chi-Minh's link above. The drug's promoters beating around the bush to avoid having it likened to other psychostimulants cannot hide the fact that it can and is being abused for similar reasons than methylphenidate. Also the manufacturer's claim that it has none of the side effects of methylphenidate may be true when therapeutic doses of modafinil are compared with abusive doses of methylphenidate but I can personally attest that modafinil taken at err, ... experimental doses carries a side effect profile that is difficult to tell from that of methylphenidate, the good and the bad. Taking into account that I'm strictly referring to oral MoA. One difference however is that modafinil is very long acting so you cannot repeatedly achieve the euphoric stage within a short period of time. This is a limiting factor for abuse but doesn't prevent it, and even prompts some users to engage in hazardous upper-downer cycles in order to be able to re-dose more often. Another claim that long onset prevents abuse is only valid as long as a user doesn't know what to expect. I know someone who sets her alarm at 4am to take the dose then goes back to sleep knowing the euphoric stage will wake her up at 6 and cut her appetite for breakfast so she can skip it. Absence of anorectic effect is also a mysth associated with the drug but it's not clear where it originates from considering the manufacturer admits appetite-suppressant effects.


----------



## pizzystrizzy

Call it what you want, but the effect sizes are lower than those produced by amphetamine and methylphenidate, more on par with atomoxetine.  In my experience, it mostly just made me wide awake.  I'm sure it helps some people, but my experience matched with what the evidence suggests happens in the majority of cases.


----------



## Kilfer

Modafinil has very little to do with atomoxetine, what is known of its biochemistry (as per Ho-Chi-Minh's link, previously cited) and physiological action, both principal and side effects, draws a profile in close relationship with methylphenidate and dextroamphetamine. The main difference however is a much delayed onset and considerably longer duration. As with many other drugs of abuse this can subjectively affect the perception of potency, a good example being methaqualone vs strong but longer-acting benzo. Modafinil's patent holder no longer denies the drug's potential for abuse (evidence produced by and for the FDA to this effect is undeniable) but claims the longer duration of unpleasant side effects such as tachycardia and sleep-deprivation induced psychosis is an effective deterrent to abuse. 

But, be that as it may, it only applies to the extent that the user won't counter the side effects by stacking with an appropriate CNS depressant/muscle relaxant 'suppressant'. Clonazepam is the drug of choice for this, but etizolam, oxazepam and even an ethanol/opiod combo are often used. All in relatively small dosage so that Modafinil blocks out recreational effects of the downers. What the abuser seeks is to be able to enjoy the positive effects of modafinil without having to pay the price on the short term. After individual calibration this allows users to abuse modafinil on a regular basis, leading to addiction.

I am 50 years old, I have been using uppers (all of them) for the purpose of work performance enhancement and, on occasion, for recreation for 35 years. I may not be a scientist but I consider myself an educated guinea pig. I can tell a real stimulant from a pseudo-stimulant like atomoxetine or buproprion. Even on paper it's obvious they won't get anyone euphoric. But modafinil can, and does for a majority of people. But some individuals are resistant, maybe you are. This can be due to natural brain chemistry, or use of other drugs, sometimes even trivial drugs like NSAID's or even certain foods can interfere with the psychoactive properties of a drug on one individual and not the next. To use myself as an example, cannabis has very little effect on me. I don't know why, but I know it's the same for certain other people.

I am not here to argue with you, if modafinil had no euphoric effect on me I would in large part share your opinion. But as the OP stated, modafinil is whacky.


----------



## pizzystrizzy

Kilfer said:


> Modafinil has very little to do with atomoxetine, what is known of its biochemistry (as per Ho-Chi-Minh's link, previously cited) and physiological action, both principal and side effects, draws a profile in close relationship with methylphenidate and dextroamphetamine.



Perhaps we are having a miscommunication here.  I am not suggesting that its mechanism of action or its pharmacological profile in general is at all similar to atomoxetine.  The only similarity I have pointed out, and the only one that really seems all that relevant to me, is that they have very similar *effect sizes* in terms of their efficacy vis-a-vis adhd symptoms.  In other words, I'm not saying that it works *like* atomoxetine, simply that it only works as well as atomoxetine.  The effect sizes for both are substantially lower than those seen with methylphenidate or amphetamine.  That doesn't mean that they don't work -- they do.  And so does bupropion, and desipramine, etc.  Modafinil appears to work better than those two, but worse than methylphenidate and amphetamine.  I'm not sure if I can make this point in any other way.



> I can tell a real stimulant from a pseudo-stimulant like atomoxetine or buproprion. Even on paper it's obvious they won't get anyone euphoric. But modafinil can, and does for a majority of people. But some individuals are resistant, maybe you are.



I don't disagree with this.  I'm sure it is more euphoric than bupropion and atomoxetine, as the latter two score lower on measures of 'liking' than caffeine.  I could even concede that it is as euphoric as amphetamine (I don't think it is, but whether and to what extent it produces euphoria is neither here nor there).  Methcathinone is a very euphoric stimulant, but I wouldn't consider it an effective treatment for ADHD.

That's really my only stake in this discussion.  The few times I tried it, I took a low dose (200 mg IIRC) and my goal was not recreational.  I found it to be similar to caffeine without the anxiety.  That's not bad -- I like caffeine and find it helpful, so caffeine that doesn't produce anxiety and lasts 12 hours is impressive in my book.  But it isn't amphetamine.  Perhaps if I had taken a larger dose it would have seemed more similar.  But at the doses tested in clinical trials, the effect sizes were smaller than those produced by d-amphetamine or methylphenidate, and nothing in my experience contradicts those findings.


----------



## Kilfer

pizzystrizzy said:


> Perhaps we are having a miscommunication here.  I am not suggesting that its mechanism of action or its pharmacological profile in general is at all similar to atomoxetine.  The only similarity I have pointed out, and the only one that really seems all that relevant to me, is that they have very similar *effect sizes* in terms of their efficacy vis-a-vis adhd symptoms.



Ah well, that changes the perspective. For my commentary was not about efficacy in treating ADHD, but abuse potential as a CNS stimulant. I admit limited knowledge about therapeutic benefits of modafinil in treating ADHD, outside of data published by various but not necessarily authoritative sources. I do not have ADHD, I was diagnosed with narcolepsy but that was back when the term included hypersomnia and chronic fatigue syndrome, conditions for which modafinil is deemed equally effective as MPH and dextro. I alternate MPH with modafinil but resist -not always successfully- taking downers with modafinil knowing it will inevitably lead to addiction.  




> In other words, I'm not saying that it works *like* atomoxetine, simply that it only works as well as atomoxetine.  The effect sizes for both are substantially lower than those seen with methylphenidate or amphetamine.  That doesn't mean that they don't work -- they do.  And so does bupropion, and desipramine, etc.  Modafinil appears to work better than those two, but worse than methylphenidate and amphetamine.  I'm not sure if I can make this point in any other way.



I get your point, I assure you. Maybe modafinil is the the proof that not all scheduled stimulants are indicated for the treatment of ADHD. I mean, not all stimulants outside of cocaine and (with one exception I think) cathinone analogs, which apparently are not useful for ADHD either, although I'm not sure why. Too short acting maybe?       



> I don't disagree with this.  I'm sure it is more euphoric than bupropion and atomoxetine, as the latter two score lower on measures of 'liking' than caffeine.  I could even concede that it is as euphoric as amphetamine (I don't think it is, but whether and to what extent it produces euphoria is neither here nor there).  Methcathinone is a very euphoric stimulant, but I wouldn't consider it an effective treatment for ADHD.



Trust me, once untoward side effects are suppressed modafinil high is barely distinguishable from amphetamine high, and lasts longer. But not as intense as coke. But therein lies the danger: modafinil side effects area easier to control. You can almost tailor the high to your liking... until sleep deprivation effects set in, and those cannot be suppressed. Personally I always keep on hand some chloral hydrate to knock me to sleep after 48 hours if I'm still up. And I don't drive after 24 hours without sleep regardless of how alert I feel.   



> That's really my only stake in this discussion.  The few times I tried it, I took a low dose (200 mg IIRC) and my goal was not recreational.  I found it to be similar to caffeine without the anxiety.  That's not bad -- I like caffeine and find it helpful, so caffeine that doesn't produce anxiety and lasts 12 hours is impressive in my book.  But it isn't amphetamine.  Perhaps if I had taken a larger dose it would have seemed more similar.  But at the doses tested in clinical trials, the effect sizes were smaller than those produced by d-amphetamine or methylphenidate, and nothing in my experience contradicts those findings.



200mg is like 5mg of methylphenidate, not enough to experience euphoria.


----------



## sekio

> Personally I always keep on hand some chloral hydrate to knock me to sleep after 48 hours if I'm still up



They still *make* that stuff?! Or are you chlorinating moonshine in your garage?


----------



## pizzystrizzy

Kilfer said:


> 200mg is like 5mg of methylphenidate, not enough to experience euphoria.



What dose for you crosses the threshold for euphoria?  And at that dose, how would you describe your ability to work on something complicated?


----------



## pizzystrizzy

sekio said:


> They still *make* that stuff?! Or are you chlorinating moonshine in your garage?



I generally prefer potassium bromide, at least when I can't get paraldehyde or ether...


----------



## Hammilton

WTF is Kilfer talking about?  Germany actually UNSCHEDULED Modafinil because it was proven not to be abusable.  Every study looking at it's effects in humans show it to be a non-abusable psychostimulant.

The fact that it binds to the dopamine transporter and inhibits reuptake is meaningless when you look at actual human studies.

The FDA scheduled it based on very bad studies (none of which actually found it TO be abused, but only that it shared characteristics that in their opinion made it likely to be abused- similarities which are meaningless in the absence of actual abuse cases).  I don't believe that there is even one case study published for modafinil abuse to date- yet I can find them for quetiapine and sulbutiamine!  lol.

There are long-onset long-duration psychostimulants with low potential for abuse which still produce definite euphoria and addiction- lisdexamfetamine being one of them.

Modafinil is not a recreational drug and never will be.  It is great for getting work done, and has black-market value as a productivity enhancer- but not as a recreational drug.


----------



## Epsilon Alpha

Hammilton said:


> WTF is Kilfer talking about?  Germany actually UNSCHEDULED Modafinil because it was proven not to be abusable.  Every study looking at it's effects in humans show it to be a non-abusable psychostimulant.
> 
> The fact that it binds to the dopamine transporter and inhibits reuptake is meaningless when you look at actual human studies.
> 
> The FDA scheduled it based on very bad studies (none of which actually found it TO be abused, but only that it shared characteristics that in their opinion made it likely to be abused- similarities which are meaningless in the absence of actual abuse cases).  I don't believe that there is even one case study published for modafinil abuse to date- yet I can find them for quetiapine and sulbutiamine!  lol.
> 
> There are long-onset long-duration psychostimulants with low potential for abuse which still produce definite euphoria and addiction- lisdexamfetamine being one of them.
> 
> Modafinil is not a recreational drug and never will be.  It is great for getting work done, and has black-market value as a productivity enhancer- but not as a recreational drug.



I got a definite mood boost out of it, not "euphoric" per say, but I definitely felt pretty damn good on it. Granted I could take up to 400mg a day and it wouldn't change from the effects I got at 50mg. It has a lot of research as an atypical antidepressant so that might be what we're feeling. 

Granted I have some weird neuro-chemistry going on... I find opioids make me anxious a hell. Caffeine helps me sleep. Nicotine is also one of the most euphoric things I've ever touched. I'm also the guy that prefers the subjective effects of pseudoephedrine to amphetamine (if it wasn't for that damn vasoconstriction...)


----------



## AlphaMethylPhenyl

Not to appeal to authority, but this guy's opinion means something: http://www.soberliving.com/resources/modafinil-provigil-stimulant-amphetamine


----------



## Hammilton

Actually it means less than nothing.  he's basing his moronic opinion on the same study that everyone else here is basing them on- the fact that modafinil raises dopamine levels by binding to DAT.  However, modafinil has an affinity weaker than bupropion which i don't see anyone claiming to be abusable (I found it incredibly dysphoric and only took two doses before I had to give up).

It's not self administered by animals, blind administration doesn't result in any liking effects- it's not a recreational drug in humans.

The fact that people use it to accomplish goals doesn't mean anything.

Millions use caffeine every day to stay up late and get work done.  The incidence of caffeinism is extremely low.  We don't have any case studies for modafinil addiction, in fact, we have hundreds describing caffeine addiction, though.

It's far less addictive than caffeine or THC.  That's saying something.


----------



## AlphaMethylPhenyl

Hammilton said:


> Actually it means less than nothing.  he's basing his moronic opinion on the same study that everyone else here is basing them on- the fact that modafinil raises dopamine levels by binding to DAT.  However, modafinil has an affinity weaker than bupropion which i don't see anyone claiming to be abusable (I found it incredibly dysphoric and only took two doses before I had to give up).
> 
> It's not self administered by animals, blind administration doesn't result in any liking effects- it's not a recreational drug in humans.
> 
> The fact that people use it to accomplish goals doesn't mean anything.
> 
> Millions use caffeine every day to stay up late and get work done.  The incidence of caffeinism is extremely low.  We don't have any case studies for modafinil addiction, in fact, we have hundreds describing caffeine addiction, though.
> 
> It's far less addictive than caffeine or THC.  That's saying something.



Oy! The number of things you _assume_!

Because caffeine has been mainstream for thousands of years?

And do a damn search, there are plenty of people who find WB abusable, me included.


----------



## Hammilton

WB?  Is this some moronic slang for wellbutrin?  I can't find any case studies confirming addiction to this drug either.  I'll look a bit more after the children are in bed, but I doubt I'll find much.

The availability of a compound certainly has an impact on the number of people who will become addicted, but the fact that after millions of prescriptions we don't have even one case study of someone actually addicted to the drug- when drugs like sulbutiamine (far less available) have already seen cases published of actual addiction.

The fact that you claim to find some euphoria from it is relatively meaningless.  If you were unable to control your use of it and became addicted to it, it would be far more meaningful.  Lots of drugs are known to cause transient euphoria in some people, it'll be listed on all sorts of drugs in the single digit % of side effects.  However, there are still zero reports of addiction to a drug.

And what exactly am I assuming?


----------



## ebola?

> WB? Is this some moronic slang for wellbutrin? I can't find any case studies confirming addiction to this drug either. I'll look a bit more after the children are in bed, but I doubt I'll find much.



As was mentioned earlier, buproprion induces fewer reports of "liking" than caffeine in studies (but that's something...it's not neutral or dysphoric).  I see how it could get 'addictive' in that after months to years of a daily regimen, there could be some clear withdrawal symptoms (the incidence being less frequent and the severity milder than with SSRIs it seems though).

ebola


----------



## AlphaMethylPhenyl

Not my experience at all.

I'm glad you understood the abbreviation.


----------



## Hammilton

Just to be clear, when I'm referring to something being addictive, i'm not in any way considering the liability to produce physical dependence.  That's a feature shared by a whole host of non-psychologically addictive compounds.  I'm referring only to a drugs ability to produce the effects and behaviors associated with psychological addiction.  I don't see anyone lying, cheating and stealing to acquire modafinil (or bupropion for that matter) or ridiculous ramping up of dose- features used in the clinical definition of addiction and present with all truly addictive drugs, the amphetamines, cocaine, opiates, etc.

If modafinil were actually addictive you'd see people forging scripts and stealing money to support their modafinil habits.  Doesn't happen- and it's not because it's so available that's its unnecessary.


----------



## ebola?

Doesn't this just suggest that "addictive" is a vague and nebulous concept, in need of clarification when used?  I concur that mere physical dependence is not enough to anchor the concept (nor is it even a necessary condition for addiction to manifest). . .and turning the discussion back toward modafinil again, I haven't seen any indications that it's addictive in any sense.

ebola


----------



## ebola?

Are they fully rested?

ebola


----------



## Tussmann

NaturalPhesta said:


> From my experience; I wouldn't deny that its possible for people to be modafinil-dependant in the short-term to complete tasks "I can't do this without modafinil, so I wont do it".



Yeah the drug is bound to downregulate or upregulate one of many neurotransmitter that cause withdrawal. Wish we knew fully what it was -- my bet is on mesolimbic DA release and up regulated GABA receptivity.


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## Engage

The times I've taken it, I rush like crazy (*booming and zooming*)and have a *horrible* come down, then, as a cherry on top, am gifted with a huge, honkin fever blister the next morning. Like clockwork. Every time. I wouldn't take it again and it nearly turned me off of all 'nootropics'.


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## Hammilton

Meh, I can take it and fall alseep immediately and continue to sleep through the night.  Did it once by accident.  It's never caused any sort of insomnia in me.


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## blueberries

I haven't read the whole thread but in my opinion it's just an orexin agonist with a few extras thrown in for good measure. It makes sense that it's the first one discovered and of course everyone runs around like headless chickens speculating upon what it could do but in the end the simplest answer is probably the right one.
And those dogs with no orexin receptors, well they probably just felt the DAT.


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## laCster

Hammilton said:


> It definitely can't.
> 
> More importantly, there are two people here I know that were going to try it for this purpose, but I haven't heard back from them.
> 
> Less useful info: when using this combination, withdrawal sets in about 15 hours after the last dose, and much worse.  Where I could usually go 30 hours without noticing any withdrawal symptoms, and 48 hours before I'd start having the horrible increase in RLS symptoms, with modafinil involved, RLS and yawning and eye-watering start kicking in after that 30 hour mark.




thank you for posting your data!! i cant take amphetamines at the time, so i am going with a nuvigil script instead to go along with my suboxone script.  im not sure if the good experiences i have had with the combo are placebo or what, but i clearly remember one time when i felt something much different from my usual dose of suboxone. i never noticed that WD set in much quicker though.. will write back more... again that is some awesome data!!


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## SpinningFree

I figured I'd weigh in on the discussion, as I've been perscribed various forms of modafinil (Cephalon Brand, US Generic, Modvigil) and even Adrafinil).  I know ancedotal evidence doesn't carry much weight, but there isn't much unbiased, pure scientific data out there and there was even less when I first had to figure out my treatment plan with my doctor years ago.  I concur with the general consensus that the Cephan brand (ie, "the real deal") seems to work the best, and has a very "clean" feeling for me, (I don't get headaches or overly jittery). Going chronologically, Adrafinil was *somewhat effective but at the standard dose, did not even come too close to producing  all the same positive effects as Provigil  at the max dose (600mg?). Then , when modafinil went generic I received a script for this and, it seemed to be reasonably effective and provided about the same benefits as the real stuff. Modvigil,is an interesting product, from our copyright-ignoring friends from India. Taken at a "usual" dose (300mg) it was not terribly effective, but bu increasing the dose (say 600) it compensated for the lack of efficacy and gave basically all the positive benefits of the real stuff.  (I can't find the quote where someone asked "Can Modvigil's weaker effect be compensated by increasing the dose?" and one poster said no, but IMO this is possible.) The only negative effects are a slight occasional headache, easy squashed with two ibuprofen. Note: A dose-increase compensation will NOT do any good past the max recommend dose of Adrafinil 

While I HAVEN'T had as much exposure is to Nuvigil, I have sampled a few doses. However, they were 100mg, on the lower end of the recommended dose. Since I experience the best effects on the upper spectrum of the dose amounts with the Cephalon product, unfortunately I cannot offer a solid opinion other than "it was decent, no negative effects at all." There's also other Indian pharmacies producing modafinil,  Modalert being mentioned as one of them. I wouldn't expect it be drastically different than the company I had sampled. 

While the Indian pharmacies haven't exactly received much praise on this thread, one of the positives about Modvigil, despite needing a bigger dose, is it lasted longer than Provigil. (upwards of 14+ hours.) Also, it passed the "urine" test but it's not quite as potent as the Cephalon brand, although this could easily be explained by how much I had to drink that day. Adrafinil lasted the shortest (6ish hours) and I often re-dosed it. I have no experience with insufflating (snorting) this substance, though it may warrant a trial in the future. I would only consider snorting the substance a "worthwhile" choice if it resulted in a significant increase in absorption vs oral (methylphenidate actually is good example).  Additionally, I did notice an increase in mood, most pronounced in the Cephalon product. Reading speed increased, as did writing. Whether or not my writing got better or just "came to me" quicker, I cannot say. Thus, I could see this as an addjunct medicine for treatment-resistent depression or possibly to counter the troublesome side- effects of an SSRI's.

While it's only been used to treat ADHD investigationally, I could see it having a decent potential to be a success. For one, it would not require re-dosing in a school setting, although this really isn't an issue for the other usual choices to treat ADHD with increased use of time-replease capsules for Ritalin, Adderall, and Dexidrine.  When dosed properly, and the drug is functioning like it should, I was highly  motivated to complete tasks, along with the ability to stay on-task for a period of time.  Of the three common "stimulant options" to treat ADHD, the only one I see even being comparable to Provigil is Dexidrine (dextro-amphetamine) and this medication is not often scripted by doctors, choosing Ritalin or Adderall instead. (ASIDE: One ADHD treatment I found actually VERY useful with essentially no negative side-effects, ironically is Desoxyn (methamphetamine.)  It's obvious why this is not a popular choice among the medical community and rarely stocked in pharmacies.. However, it was extremely effective, no jitters or increased heart rate, increased ability to complete tasks and even, IMO an increase in things like the quality of writing which isn't just a boost in top-down processing.) 

I believe this drug has a lot of potential to treat a variety of ailments. The original poster's statement that "it is the most mentally boosting drug" he's ever had I believe is accurate, (perhaps with the exception of Desoxyn).  However, the title of the post "That Wacky Modafinil" is apropos as the drug seems to change mental processing different ways in different people.  The only way to get some real good answers would be  some large-scale, longitudinal studies examining the drug's effect on different people over varied periods of time.. Or you could just see for yourself


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## Hammilton

Where do they make a 100mg nuvigil?  According to my info they make 50, 150, 200 and 250, but I see a people online saying they took 100mg, so I assume they meant provigil or took 2 50's


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## ebola?

Armodafinil is available from various vendors as a research chemical.  You also have Indian manufacturers violating copyright law.

ebola


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## Nools

Hi all ,

well, im new here, this is my first post too.

 Why in here you may be wondering, well the reason i made the account was to update my experiences of modafinil and to keep a check on the interactions with the other drugs i take (all legally). I have been taking bupe for 11 years now, started on 16mg now down to just under 4mg daily and i also take propanolol (which i stopped for my modafinil experiment), 50mg diphenhydramine every night, oh and some nitrofurantoin daily but that's neither here nor there.

I decided to try modafinil as i, for a very long time now, have had significant mental health problems that affect my concentration, ability to read, social anxiety, sleep patterns, amongst other things. I literally cannot read one page of a book any longer, my mind wanders and i have no hope of stopping it, how im meant to finish University at all never mind with a decent degree when i can't read i just don't know.

 I have in the past spent time on a psych ward, on anti-psychotics, been told i am mildly autistic/aspergers, no wait its schizophrenia, no it must be adhd... you get the idea - currently we're back to a diagnosis of as again as it runs in the family... Regardless, apparently im fucked up and no-one knows why. So im trying to help myself.

Its my first time trying modafinil today, so far i have taken 100mg. I'm definitely feeling different, much more awake, happier but not euphoric (not like speed), and fingers crossed i may even be able to read, write and get my essay handed in on time!

I'm a little concerned about the contraindications modafinil and buprenophine may have, the internet says there should be none but wiser people here in this thread seemed to think there may be. I haven't yet taken my daily dose of bupe, im trying to put it off (much more successfully than normal!) just in case.

Does anyone have any other experiences of bupe and modafinil together? im nervous about getting wd quicker than usual, i probably cant handle that...
Or any information about the mixing of the drugs i listed here and modafinil? Or any advice at all for that matter :D


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## serotonin2A

^My advice would be to talk to your doctor and develop a plan to increase your suboxone dose if you go into withdrawal before your next dose.  You might be more succeptible to an interaction because you are on a low dose of suboxone.


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## Nools

Well, that was an interesting experience... I think that might be one of the oddest things ive ever taken, wacky it certainly is!

I didn't take much, 100 mg on the first day, split into two, once at 13.00 then again at around 16.00. 
Firstly i noticed that i didn't have to run to the loo like id read i might, i was a little disappointed, ive been taking bupe for so long that i was kind of looking forward to be able to go, lol. 
It kicked in relatively quickly, id say within 20 minutes but i hardly ever eat anything so that might be why. It certainly helps with fatigue, wasn't tired once which was great. 
On the first day it didn't do much for my ability to read, cleared my mind a little, well not really cleared but quietened it down a bit which was pleasant. I noticed that i could definitely concentrate on one thing and not get distracted as easily, unfortunately it was the wrong thing (spent the day reading Bluelight, so not wasted but no essay completed...). Note for next time.. get your shit together first! Oh, and for the most part it actually made me feel pretty good, happy and calm which was great!

It did get a little weird later on though, i noticed a little bit of aggression/annoyance after my second 50mg but that passed quickly once i realised and got it in check. I oddly had no trouble sleeping at all (didn't even need the diphenhydramine), although it did kick off sleep paralysis a couple of times which is never fun . I also had a funny (both sorts) dream that this little cartoon guy (kind of looked like a minion) with a hammer was running around in my brain fixing my neurons, tbh i was rooting for him but perhaps he wasn't in there for long enough.. Oh well, there's always next time!

I took 50mg again the next day at around 15.00 and that was pretty good, i got work done and I've even managed to read half a chapter of a book which is pretty unbelievable for me so im happy. If i could increase on that it would be awesome. Didn't take any on the third day but still felt a little different and got work done too! Back to normal on the fourth day.


As for the interactions with the bupe, i waited till after 19.00 before i took it, which is normally a little late for me as it can make me a bit hyper. Well, i crapped myself, i thought it had kicked it off (which im pretty sure it cant), i felt pretty weird and was freaking out a little, but i managed to calm myself down and just ride it out. I had no wd's but i didn't get my usual buzz that i get from the bupe, which was a bit shit and put me off. Also putting me off was the fact that i had to stop my propanolol, which i don't enjoy taking but i take for occasional episodes of svt. The second night i had a too hot bath and my heart was racing like mad. Managed to stop it myself though so it was okay, but that can get a bit scary. Not sure if it was the hot bath, the moda, the lack of propanolol (which is slow release so should've lasted a while after my last dose anyway) or a combination of them.. .


I didn't write my last post correctly, my apologies. I take everything prescribed but the modafinil which i got elsewhere, oh and the diphenhydramine which i buy from the chemist. I'm getting desperate, im paying for a degree which i can't complete because i can't read. Am in my second year, have already had to resit my first, i need to sort myself out so i can complete the degree to the best of my ability and not throw my money away! 
I think there may be potential for me and modafinil but i am going to go and let the doctor know exactly what is going on and see if they are willing to help me first. I no longer get treated at the au and see my GP instead and she's normally pretty good although she knows nothing about buprenorphine and relies on me to lead the way, most of the time anyway. I'm not sure how she's going to feel about prescribing me more meds though...

Thanks for the advice , i shall mention that when i go to see her.


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## SixBuckets

I take 200mg on 3 - 4 days per week to combat extreme daytime fatigue associated with fibromyalgia. It "feels" like it's doing literally nothing, but I'm usually getting to work on time and staying awake all day. So I guess it's either effective or an extremely good placebo. 

I developed a rash after about three weeks of use, but it's not the death rash (SJS) and it hasn't gotten worse, so I'm just putting up with it.

I've heard that it's being considered as an ADHD med, but it doesn't do anything for my terrible concentration. I'm just not asleep. Oh, and the few times I have fallen asleep again after taking it, I've ended up with an excruciating headache.

I'm really interested to see that people think the generic is less effective. I've been taking a generic, but may request the brand name and see if it works better.


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## Ozle

Permission to revive this thread?


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## sekio

You kind of already did, do you have something novel to post?


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## Limpet_Chicken

Regarding chloral hydrate, yes, at least in the UK, as of 2015, it is listed in the september edition of the BNF for chloral hydrate. Its definitely still around in the UK unless discontinued within the past three years.

Edit-Ham-do you find DA agonists like pramipexole help with the RLS caused by active opioid withdrawal?


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## AlphaMethylPhenyl

Just guessing here, because there are some apparent reports of stimulants helping with RLS. But likely, not really. That is unless is broken down in NE and then E as dopamine is.


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