☠ WARNING ☠ *WARNING* Chronic ketamine/dissociative use causes bladder/organ damage

[LucidSDreamr]

The Immunomodulatory Imbalance in Patients with Ketamine Cystitis - PubMed

The pathogenesis of ketamine cystitis (KC) has been recently linked with immune response to patients but the same has not yet been established. Hence, this study aims to propose a possible immune mechanism of irreversible bladder damage caused by KC. A total of 53 KC patients and 21 healthy...

pubmed.ncbi.nlm.nih.gov

If you think the rat studies with MXE had no relevance to human pharmacology, you can't cite the results to say it's urotoxic in humans.
Also, you must either be predisposed to bladder damage on the basis that I had access to an endless amount of free MXE, courtesy of vendor I was helping (and god did I hammer it), yet really it took really really heavy ketamine use to give me a dose of bladder pain. I'd think 2-FDCK could be bad for bladder damage, as it requires doses similar to ket and lasts about as long (makes me think halogen groups at the 2 position, along with a keto group on the cyclohexyl ring are the most likely to cause damage.

I cited the study to show it damages rat bladders. It was the bulk of my disso use and it damaged my bladder. An above poster also blamed MXE for bladder dysfunction. MXE amd ketamine are similar in pharmacology. People can come to their own conclusions from these pieces of information.

I don't know if what youre implying is that the milligram dosage amount or the chemicals structure of a drug itself is what is responsible but I keep hearing people say that.

I think it's purely based on pharmacogical effect which results in immunological cascades downstream that cause the disease. This mechanism is discussed in the paper incited earlier and I have requoted above.

The structure doesn't matter. The milligram amounts put into the body being less because 3meoPCP is more potent than K doesn't matter. It's the extent of immunological response caused by the drug.

Plenty of science on non drug induced interstitial cystitis suggests similar immune based mechanisms of cystitis. Here's a paper connecting the immunological etiology of the disease and ketamines pharmacology facilitating these immune cascades. Good luck explaining that ketamine analogues like mxe don't do the same thing while having very similar targets and pharmacology, just different structures and far higher potency...knowing that it damages rat bladders and knowing there are reports of users developing the same issues as ketamine.

What is so different about mxes pharmacology from ketamine that would make you think it doesn't do the same thing ketamine does discussed in the above cited Paper?

What I see people saying is almost akin to saying that fentanyl is less likely to overdose someone because you take less milligrams of it than heroin.

Us addicts will tell ourselves anything to convince ourselves a drug is safe.

 

[Jmoda]

Are there any good supplements for bladder health/recovery?

 

[HearWhalesLaugh]

My kidneys got fucking smashed by 5 days in a week or 2Fdck. I got too damn eager after my long break and now I need to take an even longer one. At least my bag won’t be gone in record time cuz I was sure working on demolishing that shit.

Also I even had green tea extract but didn’t bother looking until the last day when I was already having small bladder symptoms. Luckily my bladder got the least of it this time but I’ve never felt my kidneys like this until now,‘accumulative damage and all that.

I’ll have to take more potent stuff and less
Often, treat it like an every 6 weeks or so treat, but my body officially won’t tolerate ketalogue binges anymore waaaaaaaaa

 

[Torresmo]

I sometimes experience difficulty peeing when I am on dissociatives. Could this alone be a symptom of bladder/urethra dammage? I never experienced pain or increase in frequency, so I thought maybe this could psychological, like a "shy bladder*.

 

[Bitchniggaz]

I sometimes experience difficulty peeing when I am on dissociatives. Could this alone be a symptom of bladder/urethra dammage? I never experienced pain or increase in frequency, so I thought maybe this could psychological, like a "shy bladder*.

Jag you were probably just to numb to feel your pipes.

First Symptoms is usually more frequent urination and/or slight pain in that area the days after use.

One big issue for alot of abusers is that taking more ket kicks the can ahead so to speak.

 

[ecstacylover]

I sometimes experience difficulty peeing when I am on dissociatives.

I used to always get that. I used DXM quite a bit before trying any other dissociatives and it was definitely the worst in that regard, but I doubt it was related to any type of long-term damage at that point.

Back in high school my friend and I would take it and go walk around the mall. One of those times I was in the bathroom trying to go for like 5 minutes and I looked over at some older gent and raised the question: "you ever been so fucked up you can't piss?" He nodded as if he understood but I'm not sure he did.

 

[RegionalDissociateManager]

Bladder issues seem pretty widespread geographically with people around the world being affected. I don't know how to explain that unless the entire worlds supply of ketamine is coming from a single source (not that I know anything about the illicit ketamine supply chain, maybe it does come from a single source).

Most samples on drugs data just show ketamine and leftover precursor whatever that entails.

I'd be inclined to side with the hypothesis that people just take a lot more ketamine these days and that's led to more reports of this kind emerging. Compounded as you said by cheap easy access to the drug but also by the fact that everyone has broadband and smartphones so word spreads faster than 20 years ago. What else can we assume unless something weird and identifiably bladder melting shows up in a lab test?

This is your ketamine precursor A:

1-(2-Chloro-N-methylbenzimidoyl)cyclopentanol​

Seems as if you just need to heat that with a solvent with a high boiling point, with no other chems, and you get k.

That could be where alot of the impurity is coming from, backyard chemists not hearing off enough of the precursor.

Hard to find much info on the precursor though, especially in terms of health effects. They list 100mg of precursor for $750 though, so I don't see how that could ever make sense for anyone.(Alrhough precursor A is in almost every sample on drugsdata, so it must make sense somewhere.)


Edit: Upon further digging, there are 2 other known 'precursors'. One source actually named them impurities, and I haven't researched these other two at all, so I'll use the term precursor lightly here for B and C; they may just be impurities. These are even considered allowed impurities in pharmaceutical grade stuff, but in extremely limited quantities, fractions of a percent. I'm sure the percentage of impurity in illegal synthesis is much greater on almost every occasion. Maybe someone on here will have some extensive knowledge on this specific topic.

Impurity B: (2RS)-2-(2-chlorophenyl)-2-hydroxycyclohexanone

Impurity C: (2-chlorophenyl) (1-hydroxycyclopentyl)methanone

Interestingly enough: neither B, or C have ever been detected in a sample on drugs data; maybe these are cooked off at lower Temps, and precursor A is a little more resiliant, causing larger instance of greater impurity/ bladder issues

 

[Xorkoth]

I used to always get that. I used DXM quite a bit before trying any other dissociatives and it was definitely the worst in that regard, but I doubt it was related to any type of long-term damage at that point.

Back in high school my friend and I would take it and go walk around the mall. One of those times I was in the bathroom trying to go for like 5 minutes and I looked over at some older gent and raised the question: "you ever been so fucked up you can't piss?" He nodded as if he understood but I'm not sure he did.

Interesting, as far as I know, DXM does not share the bladder-damaging properties of ACH dissos. However, pretty much all serotonin reuptake inhibitors and releasers make it harder for me to pee temporarily.

 

[ecstacylover]

Interesting, as far as I know, DXM does not share the bladder-damaging properties of ACH dissos. However, pretty much all serotonin reuptake inhibitors and releasers make it harder for me to pee temporarily.

Yea, I always found it a bit odd that the urinary retention I got on DXM was much worse than anything I ever got on ACH's, which are known for being bladder toxic. Generally though DXM is much harder to daily abuse than ACH's though, so I wonder if that has something to do with it.

On the previous page I linked a Nature paper from last year that showed ketamine inhibits bladder contractility by inhibiting an L-type calcium channel (Cav1.2), and they also showed this leads to cystitis by disrupting calcium-mediated transcription. In addition they showed Cav1.2 knockout could mimic ketamine cystitis. Interestingly, all of the effects were independent of NMDAr antagonism.

The reason I mention that is because I thought surely DXM/DXO are structurally different enough from ketamine that it's unlikely they would also inhibit L-type calcium channels, but when I went and looked it up there is evidence that they do! There's a catch though, the effect was pretty weak (IC50 of 100uM), whereas the ketamine paper I mentioned above the IC50 appears to be somewhere around 1uM, so perhaps that could underlie why ketamine is known for being bladder toxic and DXM isn't? Although I'm not sure the comparison is valid considering the papers used quite different methods.

 

[NeuroDr]

I’ve been using dissos quite regularly for a long time. Ketamine mostly, and haven’t noticed any issues with my bladder. I really should ease off them. Always low dose to kind of ease anxiety

 

[plumbus-nine]

Interesting, as far as I know, DXM does not share the bladder-damaging properties of ACH dissos. However, pretty much all serotonin reuptake inhibitors and releasers make it harder for me to pee temporarily.

DXM is a psychotic beast and gives me acoustic hallucinations from hell now once I have acquired permatolerance to dissociatives. None of the ACH structure dissociatives are psychotomimetic in this amount to me, I can still do DCK, DMXE etc in grams and not getting anywhere near to what 500mg DXM do to me. I don't want to know what this poor individual forgot about his trip when he kept hearing "DON'T DO THIS TO ME AGAIN" for many hours (it's in the DXM FAQ).

I’ve been using dissos quite regularly for a long time. Ketamine mostly, and haven’t noticed any issues with my bladder. I really should ease off them. Always low dose to kind of ease anxiety

Not everybody gets bladder problems and not everybody in the same amount, I'd read these rat studies with some grains of salt and still believe that either an abundant impurity or one K isomer with its relative impotency compared to most other ACHs itself is specially toxic. Nice to finally see what chemical compound this famous 'precursor A' is. Says a lot about the situation drugs are in when this wasn't known for so long.

Yea, I always found it a bit odd that the urinary retention I got on DXM was much worse than anything I ever got on ACH's, which are known for being bladder toxic. Generally though DXM is much harder to daily abuse than ACH's though, so I wonder if that has something to do with it.

On the previous page I linked a Nature paper from last year that showed ketamine inhibits bladder contractility by inhibiting an L-type calcium channel (Cav1.2), and they also showed this leads to cystitis by disrupting calcium-mediated transcription. In addition they showed Cav1.2 knockout could mimic ketamine cystitis. Interestingly, all of the effects were independent of NMDAr antagonism.

Urinary retention != bladder damage. But it indeed is independent from NMDAr antagonism, the high potency ACHs are almost devoid of urotoxicity because of the little amounts and in the same way is K the worst one. Interesting to hear about the Cav1.2 stuff, I thought of DXM urinary retention to be a result of anticholinergic activity, as well as my disturbing hallucinations from it.

 

[ecstacylover]

Not everybody gets bladder problems and not everybody in the same amount, I'd read these rat studies with some grains of salt and still believe that either an abundant impurity or one K isomer with its relative impotency compared to most other ACHs itself is specially toxic. Nice to finally see what chemical compound this famous 'precursor A' is. Says a lot about the situation drugs are in when this wasn't known for so long.

In most of those samples ketamine is present in 10x the amount of precursor A, and sometimes much more. What's more likely, that a compound which is demonstrated in pure form to damage bladder tissue, or that a precursor which is present in 10x or lower concentrations is doing the damage?

MXE gave me the worst bladder symptoms of any ACH I've tried (and it's also been shown to be bladder toxic in vitro+ in vivo), and others have reported it with 3-MeO-PCP as well. I don't think it's at all obvious that other ACH's won't be just as bad your bladder. It's just that far more people use K, so of course there's going to be more documented cases. It's true that not everyone has issues but this probably boils down to differences in individual immune systems. Not everyone gets asthma, etc..

 

[plumbus-nine]

What's more likely, that a compound which is demonstrated in pure form to damage bladder tissue, or that a precursor which is present in 10x or lower concentrations is doing the damage?

Both. I acknowledge that arylcyclohexylamines are urotoxic, this has formal proof (at least in rats, which don't make the best model). But it isn't the NMDA antagonism but something about the ACH structure which makes them toxic, and this means that 10% impurity can well be stronger than 90% ketamine (see the potency of some ACHs like the PCP analogues). At least I got those infamous K-stomach-cramps only once, when I was going through 25g of illicit K within a few days - without holing. Another batch of K didn't do that. Also I did similar binges with more potent RCs and didn't get much discomfort at all.

But indeed there is urotoxicity present even with pure MXE. Would be good to find an antagonist to that. Anybody any clue?

 

[ecstacylover]

(at least in rats, which don't make the best model).

How so? If we can learn about the human brain with rat models, we can surely learn about peripheral systems (which have diverged far less from rodents to primates). Yes there are slight differences in protein sequences and binding affinities between rodents and humans but the signaling systems and overall strategies will be highly conserved.

Also, the methoxetamine in vitro studies specifically looked at human bladder tissue as well, and it was damaging. I don't doubt that there's studies that have done the same with ketamine.

But it isn't the NMDA antagonism but something about the ACH structure which makes them toxic

The bladder toxic effects may be NMDAr independent in some experimental models, but this doesn't mean the entire pathophysiology is.

The bladder pain thought to be caused by abnormal nerve growth around the bladder, and this could be mediated by the increased serum levels of BDNF. Ketamine elevates brain BDNF via an NMDAr-dependent pathway, so it's not out of the question that peripheral BDNF elevations correlate with NMDAr affinity.

and this means that 10% impurity can well be stronger than 90% ketamine

Anything is possible, but this is complete speculation with no experimental evidence.

 

[LucidSDreamr]

Are there any good supplements for bladder health/recovery?

No the damage is permanent if you have it.

You simply have to manage symptoms using meds and various treatments.

You'll find plenty of supplements. Y searching but none of them are going to result thr GAG wall of the inside of the bladder or repair scaring and glomerularion. Snake oil imo, there are some research around Supporting hyaluronic acid but ppl.dont seem to notice a benefit when you ask them.

Things ppl will tell you like cranberry juice and green tea will worsen your symptoms.

Interstitial cystitis Diet is probably the biggest key to avoiding symptom flares.

 

[Vastness]

I will say, and this is not harm reduction related advice, just an observation, that since reducing the amount of protein in my diet, finally managing to quit the job that was killing me with stress, and entering a new relationship with a girl who is not a huge fan of my sporadic drug habits but is fairly understanding, although I absolutely never use profoundly altering ones around her - despite the fact I have not managed to quite my occasional use of arylcyclohexylamines, which is something that bothers me slightly in it's own right - while I still experience frustrating urinary retention issues from them, depressive brain fog for days after some of them (ketamine, primarily) and do not feel that they are particularly healthy for me, physically, in any way - I no longer experience acute bladder or kidney symptoms of any kind, either during the experiences on the comedown, or any kind of pain, increased bladder awareness, symptoms of reduced bladder capacity, or really, anything, during the days after.

I was previously consuming about 33% protein as far as macronutrient intake - I think this was too much and was the primary strain on my kidneys, which my occasional arylcyclohexylamine use exacerbated. I am not exactly tracking my nutrient intake in nearly as disciplined a way as I once was but although my diet is probably less "healthy" in terms of the actual foods I'm eating, it is made up of a far higher proportion of carbohydrates. I could probably work out the exact figures but I intend to just make this post fairly quickly so I'll just say right now I don't really know my macronutrient ratio but it is probably closer to 20% protein.

In retrospect - I think for myself a very big part of my bladder symptoms was immense and continuous life stress and a big element of nocebo given my awareness of the bladder dangers. I do make sure to take an ECGC supplement on any day I use arylcyclohexylamines though - I did this before as well, as soon as finding out the benefit, but it did not, on it's own remove the side effects in the way that massively simplifying my life and removing several sources of major stress appears to have done so.

I understand that life stress is very often not something that is too easy to remove - if it was, far fewer people would have any of it. But for me, this, too high protein intake for my physiology over an extended period and finding myself simply worrying less about the bladder dangers after a fairly high biomarker quantity test of my bladder and kidney functions that did not spot anything strange and actually seemed to indicate my kidneys were functioning better than average despite the fact that I took the test maybe a day after a ketamine binge, seems to have provided a psychological reassurance and removal of strongly noceboing psychological stressors that means my concern over my continued arylcyclohexylamine use is now more about the effects on my brain and, with the newer ones with less human use, other unforeseen effects on my physiology than it is about causing permanent damage to my bladder.

That said - this post is intended to provide a datapoint and nothing else. The bladder dangers of the arylcyclohexylamine class are, at this point, a fact. My own experience will not be the same for everyone - some physiologies do appear to be especially vulnerable to the bladder toxicities of this class. But equally for some people - how many people, or what people, is currently impossible to quantify - my experience has lead me to believe that awareness of the reality of these dangers does somehow trigger some kind of nocebo in certain people that makes these potential dangers reality. And, vice versa, the power of the human brain in exerting inexplicably curative and protective effects against physical ailments is very poorly understood - it may be moreso that in some people, some kind of placebo and removal of concern about these dangers has a beneficial effect in cancelling them out.

I do not believe, however, that either of these latter scenarios are consciously controllable. Again, this post is a datapoint only - not any kind of advice, not a dismissal of the dangers of this class, and not any kind of advice to anyone to change the way they use this class in any way, because the reasons for my own experience are still impossible to really clarify or understand.

 

[Chris Timothy]

Vasty, have you ever considered going keto?

 

[LucidSDreamr]

I support the creation of this sticky thread as I would like to learn more.

I've used ketamine therapy for depression, albeit at low dosage levels, and I would like to hear more stories about how dissociative use affects the urinary system. My concern is that the dangers are not just limited to heavy use, but any use.

This is old post so sorry if I already mentioned it but I believe one of the articles I mentioned in the OP documented liver injury in a clinical administration program, not illicit abuse.

 

[LucidSDreamr]

I will say, and this is not harm reduction related advice, just an observation, that since reducing the amount of protein in my diet, finally managing to quit the job that was killing me with stress, and entering a new relationship with a girl who is not a huge fan of my sporadic drug habits but is fairly understanding, although I absolutely never use profoundly altering ones around her - despite the fact I have not managed to quite my occasional use of arylcyclohexylamines, which is something that bothers me slightly in it's own right - while I still experience frustrating urinary retention issues from them, depressive brain fog for days after some of them (ketamine, primarily) and do not feel that they are particularly healthy for me, physically, in any way - I no longer experience acute bladder or kidney symptoms of any kind, either during the experiences on the comedown, or any kind of pain, increased bladder awareness, symptoms of reduced bladder capacity, or really, anything, during the days after.

I was previously consuming about 33% protein as far as macronutrient intake - I think this was too much and was the primary strain on my kidneys, which my occasional arylcyclohexylamine use exacerbated. I am not exactly tracking my nutrient intake in nearly as disciplined a way as I once was but although my diet is probably less "healthy" in terms of the actual foods I'm eating, it is made up of a far higher proportion of carbohydrates. I could probably work out the exact figures but I intend to just make this post fairly quickly so I'll just say right now I don't really know my macronutrient ratio but it is probably closer to 20% protein.

In retrospect - I think for myself a very big part of my bladder symptoms was immense and continuous life stress and a big element of nocebo given my awareness of the bladder dangers. I do make sure to take an ECGC supplement on any day I use arylcyclohexylamines though - I did this before as well, as soon as finding out the benefit, but it did not, on it's own remove the side effects in the way that massively simplifying my life and removing several sources of major stress appears to have done so.

I understand that life stress is very often not something that is too easy to remove - if it was, far fewer people would have any of it. But for me, this, too high protein intake for my physiology over an extended period and finding myself simply worrying less about the bladder dangers after a fairly high biomarker quantity test of my bladder and kidney functions that did not spot anything strange and actually seemed to indicate my kidneys were functioning better than average despite the fact that I took the test maybe a day after a ketamine binge, seems to have provided a psychological reassurance and removal of strongly noceboing psychological stressors that means my concern over my continued arylcyclohexylamine use is now more about the effects on my brain and, with the newer ones with less human use, other unforeseen effects on my physiology than it is about causing permanent damage to my bladder.

That said - this post is intended to provide a datapoint and nothing else. The bladder dangers of the arylcyclohexylamine class are, at this point, a fact. My own experience will not be the same for everyone - some physiologies do appear to be especially vulnerable to the bladder toxicities of this class. But equally for some people - how many people, or what people, is currently impossible to quantify - my experience has lead me to believe that awareness of the reality of these dangers does somehow trigger some kind of nocebo in certain people that makes these potential dangers reality. And, vice versa, the power of the human brain in exerting inexplicably curative and protective effects against physical ailments is very poorly understood - it may be moreso that in some people, some kind of placebo and removal of concern about these dangers has a beneficial effect in cancelling them out.

I do not believe, however, that either of these latter scenarios are consciously controllable. Again, this post is a datapoint only - not any kind of advice, not a dismissal of the dangers of this class, and not any kind of advice to anyone to change the way they use this class in any way, because the reasons for my own experience are still impossible to really clarify or understand.

Stress is a major part of the manifestation of interstitial cystitis symptoms or flares...where the damage was caused by ketamine or genetics but stress will flare you. The reasons are twofold.

1) stress activating cytokine responses which are also a product of immune response and these elements have been linked in the scientific literature to the etiology of non ketamine interstitial cystitis which is indistinguishable from ketamine cystitis for doctors as far as diagnostic tests go.

2) stress causes tightening of the pelvic floor similar to clenching your jaw when stressed. The plevic floor clench adds pressure to the bladder and can tip a slightly inflamed but asymptomatic bladder to the point where symptoms like pain or reduced capacity are noticed. Then the bladder pain creates a nasty feedback loop to clench the pelvic floor and they reinforce eachother.

With my issues I have to force myself to be aware of my pelvic floor or else it automatically clenches (does a Kegal basicslly) as it's natural state of being

 

[Jmoda]

T

This is old post so sorry if I already mentioned it but I believe one of the articles I mentioned in the OP documented liver injury in a clinical administration program, not illicit abuse.

One of the biggest lies that has been engrained in our society, I think, is that things are either/or - binary. When in reality every single things is a probabilistic distribution around said mean. Which means there will be some that get very noticeable and severe bladder damage even with minimal use, and some will be totally fine even with chronic daily use. All that is to say, try and know and hear your body as best as possible to know where along that distribution you are.