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

Buzz Lightbeer

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I like to hole... I take it K is the best option?

I hear 2-fdck is pretty good for this stuff but why elonage the timelessness of a K experience?
I heard some people LOVED 3, 4 meo shit.

MY FRIENDS THINK I AM LOONY TUNES BANANAS PSYCHO-CRAZY FOR EVEN ATTEMPTING a top-level K hole and REPEATING THE EXPERIENCE and loving it

...how could ANYONE stay holed for 2 weeks in a row is beyond my comprehension.

Aeon please share details, hard-heads want to know more.
The 3-meos are very hard to hole on, most people don't even attempt it. They're very stimulating and mania inducing.
 

Chris Timothy

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Went to a random mushroom ceremony once and the shaman of service was on one of those, 3 or 4 can't remember which. When we talked it turned into the most unhinged conversation ever. He basically became possessive about a goddamn brick of milk. For no reason. I tried to give the milk purpose because it looked so important to you that it apparently had to become important to me too. That doesn't mean I'm stealing the milk. I have coffee in front of me and you're parading a carton of milk as some hunting trophy, you didn't leave much room for alternatives. Yes I'll take care of the hunting trophy now, I shall return it to the place where coldness reigns when I'm done, the fridge is right there I can see it.

He did quit that job right after.
 

Survived Abortion

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I’ve done a lot of reading on this, and it seems there are two mechanisms at work here that cause the syndrome.

The first is that ketamine apparently activates thioredoxin interacting protein (TXNIP) and the NOD-like receptor protein 3 (NLRP3) in the bladder endothelium. These are essentially detoxification and immune regulating mechanisms, which are switched on or off variously to deal with toxins and bacterial infection.

NLRP3 activates in the presence of pathogens as an immune response, but is also switched on by various chemicals and drugs. The result is the release of reactive oxygen species (ROS) and apoptosis of the endothelial cells.

TXNIP is part of the redox mechanism and regulates the activity of thioredoxin, one of the body’s powerful antioxidants. When TXNIP is activated by ketamine, thioredoxin is suppressed which is bad. TXNIP over-activation is also involved in extra-cellular matrix deposition and thus fibrosis and scarring.

These proteins react to high glucose environments, which is why they are implicated in diabetes mellitus.

The second mechanism at work is that ketamine increases the amounts of nerve growth factor (NGF) in the bladder endothelium and muscle, whilst increasing substance P concentration (the pain molecule). This serves to massively increase the concentration of nerves in the bladder making it a lot more sensitive and receptive to pain than before. It also affects the holding capacity.

Perversely, it seems as though the same mechanism that makes ketamine such a great brain fertiliser (by increasing BDNF and neural plasticity) also causes the runaway proliferation of nerves in the bladder.

It was apparently found that “knocking down” TXNIP prevented damage to human bladder cells, preventing the activity of NLRP3 and cell apoptosis.

—-

So it seems to me that in order to deal with this horrible side-effect of arylcyclohexylamines, a user should co-administer it with a compound that somehow inhibits NLRP3 or TXNIP. And it turns out there are quite a few candidates out there for that.


Naturals:

Ba-Wei-Die-Huang-Wan (Hachimi-Jio-Gan) - stops ketamine-induced bladder damage. Inhibits the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity https://www.ncbi.nlm.nih.gov/m/pubmed/31541501/

Rhabdosia Rubescens - oridonin - NLRP3 inhibitor https://www.ncbi.nlm.nih.gov/m/pubmed/29959312/

Feverfew (Asteraceae) - parthenolide - NLRP3 inhibitor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842943/

Quercetin, luteolin and epigallocatechin gallate- flavonoids found in many herbs, such as chamomile and green tea. https://www.ncbi.nlm.nih.gov/m/pubmed/25446924/

Turmeric (curcumin) - anti-fibrotic, anti-oxidant https://www.ncbi.nlm.nih.gov/m/pubmed/25054130/

Synthetics:

Verapamil - calcium channel blocker and TXNIP inhibitor

I’m not comfortable with promoting the use of synthetic pharms to counter ketamine-bladder. But perhaps if we understand why they work, we can find natural alternatives which do the same job.

Verapamil is a commonly-prescribed anti-hypertensive which works as a calcium-channel blocker, and is known to prevent the actions of NLRP3 from causing apoptosis. It has anti-diabetic effects due to this mechanism, and it’s just speculation but it may also work to prevent ketamine-bladder.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628557/

There are many calcium-channel blockers in the herbal world though, and it would be much better to find a natural solution. Actually a lot of foods are calcium channel blockers, so this may partially account for the differences in people’s reported reaction to ketamine in this way.

Another possible candidate is quinine (found in tonic water) and other alkaloids of the cinchona tree. Quinidine and quinine (from cinchona) are sodium-channel blockers and could therefore prevent NLRP3 from destroying cells. Quinine may also prevent potassium efflux. This is just pure speculation though.

Other possibilities are medicines which prevent potassium efflux (as quinine above). It seems that this mechanism is very important in preventing the damage associated with NLRP3 activation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392179/
 

G_Chem

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Amanita Muscaria gave me a bigger holing experience than MXE ever could.

Mushrooms add a little something extra. Also kinder for the kidneys.

Any more info on this?? I’ve been very curious of the Amanita having found them many times over the years while mushroom hunting. The varied reports have kept me from trying them but any positive reports I like to hear.

You eat em fresh or dried? Any preparation advice?

-GC
 

Aeon Psyche

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I Always heard that eating amanita muscaria is deadly if they are still fresh. Needing to dry them completely before consumption. I've only smoked it together with a few other herbs in the past. I don't have any remarkable experience that I can tell you about. I did however had lucid dreams that night but it might have been the mushrooms (Psilo(cyb)in truffels) I ate the night before.
 

GearoftheYear

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Another possible candidate is quinine (found in tonic water) and other alkaloids of the cinchona tree. Quinidine and quinine (from cinchona) are sodium-channel blockers and could therefore prevent NLRP3 from destroying cells. Quinine may also prevent potassium efflux. This is just pure speculation though.

It is common among my friends to drink beer with ketamine to counter act some of the negative side effects. This works for them but has the opposite effect for me. I don't encourage it so never speculate on it much but I'm glad to see some alternatives.

Most of this information was new to me but it's interesting you mention quinine. I found it a great aid for calming any cramps, vomiting or similar issues from ketamine. It doesn't calm symptoms enough to create a scenario to consume more ketamine but it can be the difference between a 1-2 vs 3-4 day recovery.

Even after breaking for two or three months my tolerance was still way up and 300+mg lines didn't really result in any decent holing.

It is probably worth a break PYTH. MXE tolerance destroyed ketamine in a lot of ways for me and I imagine DXM would also.

Re 3-meo-pcp, it can still send me into uncontrollable delusional style paranoia/mania after multiple doses over 2-3 days. I could never hole on it unless on a hole dose of another dissociative. I agree it's very cold, I didn't find it enjoyable unless it was the first 12 hours or so during the intial controllable mania. I would discourage anyone from using without at least someone aware of what you're up to, frequency of dosing and to hold reality together when it falls apart. I never noticed bladder issues from it other than increased urinating although it always felt less clean than ket/mxe when exceeding a low dose. It also really messes with your perceptions, similar to diazepam you'll feel sober but you're out of it. Affects muscle coordination when getting to mid-high doses in a subtle but powerful way.

It's certainly not what I would see as a ketamine alternative.

--

Anyone know of common ketamine cutting agents nowadays? Other than the obvious msg, sugar, salt, vanilla extract.

When looking at test results of batches that have been regional wide, as often is the case the major name (ketamine) is given but the minor adulterants aren't named. MPA/DMPA is the only new adulterant I've read from a test result. Purity ranged between ~65-85%, the source of these test results is no longer available. Wedinos tests levamisole in references including W012663 which looks rocky in the photo.

I'm not sure what the cutting agents are but at worst they increase vomiting, cramps and stress on kidneys. Most people don't notice it and aren't dissolving any of their last gram or two in water to check.

I think a combination of cutting agents and poor lifestyle choices when using ketamine could increase the cramp and kidney issues. The cutting agents don't seem to affect urinating/bladder but a combination of ketamine, the adulterant and self neglect introduces UTIs and other problems.

Misinformation is also a massive issue, users aren't aware of purity and cuts, myself included. It still seems to be a common misconception both online/offline that ketamine isn't cut when it's been stepped on multiple times. Even vials aren't guaranteed in Europe, unless it's one or two hand picked from a pharmacy, anyone can buy vials and adulterated k to make 'veterinary' ketamine. I'm glad to see more concrete evidence coming from studies that will hopefully change this over the next few years.
 
Last edited:

PYTH

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I wandered into an old thread searching for something at the apparent height of the MXE craze and holy crap people were doing a ton of it. Lots of 'guys, my bladder is starting to feel weird' without anyone having any context 😨

Having never done it was it that much more addictive? What was the appeal, a better hole? More stimulating?
 

Chris Timothy

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I Always heard that eating amanita muscaria is deadly if they are still fresh. Needing to dry them completely before consumption. I've only smoked it together with a few other herbs in the past. I don't have any remarkable experience that I can tell you about. I did however had lucid dreams that night but it might have been the mushrooms (Psilo(cyb)in truffels) I ate the night before.

They're not likely to kill you. You'd have to be a child or an elderly, or eat more than a dozen caps or so.

I wandered into an old thread searching for something at the apparent height of the MXE craze and holy crap people were doing a ton of it. Lots of 'guys, my bladder is starting to feel weird' without anyone having any context 😨

Having never done it was it that much more addictive? What was the appeal, a better hole? More stimulating?

Better than heroin, some said. Tried some opioids yesterday, stuff that should at least be as good as heroin, and it's quite crap in comparison indeed.

Basically MXE gave all the dissociation you want, so whatever pain you had stopped being the dominating variable. Yet the heavy serotonergic effect kept you in harmony with the outside world nevertheless.

I’ve done a lot of reading on this, and it seems there are two mechanisms at work here that cause the syndrome.

The first is that ketamine apparently activates thioredoxin interacting protein (TXNIP) and the NOD-like receptor protein 3 (NLRP3) in the bladder endothelium. These are essentially detoxification and immune regulating mechanisms, which are switched on or off variously to deal with toxins and bacterial infection.

NLRP3 activates in the presence of pathogens as an immune response, but is also switched on by various chemicals and drugs. The result is the release of reactive oxygen species (ROS) and apoptosis of the endothelial cells.

TXNIP is part of the redox mechanism and regulates the activity of thioredoxin, one of the body’s powerful antioxidants. When TXNIP is activated by ketamine, thioredoxin is suppressed which is bad. TXNIP over-activation is also involved in extra-cellular matrix deposition and thus fibrosis and scarring.

These proteins react to high glucose environments, which is why they are implicated in diabetes mellitus.

The second mechanism at work is that ketamine increases the amounts of nerve growth factor (NGF) in the bladder endothelium and muscle, whilst increasing substance P concentration (the pain molecule). This serves to massively increase the concentration of nerves in the bladder making it a lot more sensitive and receptive to pain than before. It also affects the holding capacity.

Perversely, it seems as though the same mechanism that makes ketamine such a great brain fertiliser (by increasing BDNF and neural plasticity) also causes the runaway proliferation of nerves in the bladder.

It was apparently found that “knocking down” TXNIP prevented damage to human bladder cells, preventing the activity of NLRP3 and cell apoptosis.

—-

So it seems to me that in order to deal with this horrible side-effect of arylcyclohexylamines, a user should co-administer it with a compound that somehow inhibits NLRP3 or TXNIP. And it turns out there are quite a few candidates out there for that.


Naturals:

Ba-Wei-Die-Huang-Wan (Hachimi-Jio-Gan) - stops ketamine-induced bladder damage. Inhibits the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity https://www.ncbi.nlm.nih.gov/m/pubmed/31541501/

Rhabdosia Rubescens - oridonin - NLRP3 inhibitor https://www.ncbi.nlm.nih.gov/m/pubmed/29959312/

Feverfew (Asteraceae) - parthenolide - NLRP3 inhibitor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842943/

Quercetin, luteolin and epigallocatechin gallate- flavonoids found in many herbs, such as chamomile and green tea. https://www.ncbi.nlm.nih.gov/m/pubmed/25446924/

Turmeric (curcumin) - anti-fibrotic, anti-oxidant https://www.ncbi.nlm.nih.gov/m/pubmed/25054130/

Synthetics:

Verapamil - calcium channel blocker and TXNIP inhibitor

I’m not comfortable with promoting the use of synthetic pharms to counter ketamine-bladder. But perhaps if we understand why they work, we can find natural alternatives which do the same job.

Verapamil is a commonly-prescribed anti-hypertensive which works as a calcium-channel blocker, and is known to prevent the actions of NLRP3 from causing apoptosis. It has anti-diabetic effects due to this mechanism, and it’s just speculation but it may also work to prevent ketamine-bladder.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628557/

There are many calcium-channel blockers in the herbal world though, and it would be much better to find a natural solution. Actually a lot of foods are calcium channel blockers, so this may partially account for the differences in people’s reported reaction to ketamine in this way.

Another possible candidate is quinine (found in tonic water) and other alkaloids of the cinchona tree. Quinidine and quinine (from cinchona) are sodium-channel blockers and could therefore prevent NLRP3 from destroying cells. Quinine may also prevent potassium efflux. This is just pure speculation though.

Other possibilities are medicines which prevent potassium efflux (as quinine above). It seems that this mechanism is very important in preventing the damage associated with NLRP3 activation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392179/

That's great! Now all we need is a proper function for bladder feeling. =D
 

Vastness

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@Survived Abortion, thank you for posting all that stuff, that is very interesting indeed.

It is common among my friends to drink beer with ketamine to counter act some of the negative side effects.
Could you elaborate which side effects you mean? Bladder feelings? Or urinary retention, perhaps? Is it supposed to counter the actual damage in some way...? Or just the feelings?

Just curious as I had a somewhat harebrained idea a while back to drink diuretics while I was doing ketamine such as caffeine, or beer, to potentially empty my bladder more often and thus protect against damage. I felt at the time that maybe it helped but in retrospect this was probably just placebo.

Anyway personally now I always find beer ruins that lucid psychedelic edge I like to feel when doing ketamine, but it probably would help with urinary retention.
 

Vastness

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I guess it makes some sense in theory, especially given the bladder damage seems to be at least partly related to contact of ACH-contaminated urine with the bladder wall. I was informed by someone last time I mentioned it though that dissociatives, at least the ACH ones, are themselves diuretics - so realistically there is probably a ceiling effect as far as how much "diuresis", if that's the term, can actually be induced. Additionally, even if there is something to it, excess and deliberate dehydration in an effort to protect the bladder is going to exacerbate stress on the kidneys and any other organ systems that are at risk... so maybe not ideal. Granted, maybe there is some kind of dose balance where there is some kind of small benefit, perhaps where the diuretic effects of the dissociative are not so prominent, or threshold doses, as you say. I'm inclined to think it wasn't much use for my usual preference of successive 250mg+ hole inducing doses.
 

Chris Timothy

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Of course stimulating diuresis is futile while holing? You're a silly person sometimes, Vasty.. 🤪

Is there even any other disso user who's skeptical towards hydration as harm reduction?
 

Vastness

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Not skeptical towards the idea of hydration as harm reduction, but I thought we were discussing dehydration, via use of diuretics to speed up emptying the bladder and, presumably, minimise urine production after a certain point - no?

Obviously when completely immobile, diuretic effects might be considered somewhat irrelevant, but usually during a session there would be ample opportunities between holes to empty my bladder and take advantage of any potential benefits of having as empty a bladder as possible for as much of the duration of the experience as possible - whether those benefits are real or not.

I was also thinking that at the point that dosages are sufficient to induce a hole, they're probably also sufficient that the diuretic effects induced by the substance itself (ketamine, or another), would be sufficient that the addition of extra diuretics such as alcohol or caffeine would no longer be desirable - if it ever was - but again, I have no data to support this and suspect it might be a moot point anyway, just speculating.
 

Cream Gravy?

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I never had trouble staying hydrated/getting up out of holes on MXE to piss. I think that these bladder damage issues are more due to amount of material consumed, both short and long term. I did MXE for about two years on and off, sometimes spaced out, sometimes multiple nights. Never had any issues, no matter which batch I was on.

I'm weird about hydration though; I always have a one liter bottle of water with me, I drink 3-5 per day and have for years.
 

Chris Timothy

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Hmm yeah bad example, we don't have clear consensus on the meaning of holing. I myself would take being able to attend to bathroom business as a clear sign I'm not holing, but I suppose YMMV.

@Vastness
I could have sworn you had expressed skepticism about it in the past.. I remember being baffled to the point of silence over it, but I might have misunderstood, or might be misremembering. But you do keep ending up with these kinda statements which keep raising my eyebrow to various degrees of height! It seems to keep coming down to an implicit conception of the organism as dumb mechanism, rather than as an expression of the intelligence of the universe. Because for a dumb machine diuresis would mean dehydration. Yet for a system with even just one more feedback loop on top, diuresis could easily be made to mean increase in water throughput.

I don't know whether ACHs suppress vasopressin as well.. probably not, because it's mainly ethanol's action at the ion channels that's doing the trick here. But again, you're just blatantly ignoring that psyche could mediate this process, that diuresis here is set in motion by the organism playing the subconscious program of getting rid of a general poison. You're almost never completely wrong, but these small inaccuracies in your reasoning stack up so the end picture gets out of focus, if that makes sense.

And it's as if I'm singling you out over this, but I really shouldn't. The same thing happens in climate science: even more processes on the planetary scale to gaze oneself blind on than those confined within the skin. Because if the analytical excursions aren't brought back to the perspective of an integrated system which jumps homeostatic states, then we end up with a view in which we justify trashing the place. Cuz why not treat a dumb rock like a dumb rock, right? Well, turns out geology forms an engine principle in evolution, and is as such inextricably entangled with intelligent process. I made NASA change their mind on chemically evolved AI which therefore wouldn't work, as you can't put chemistry in a box with the engine principle abstracted away without inevitable consequences. Point being that analytical trains of thought even get the smartest people in the world sidetracked, and in the end you really can't substitute research for vision. Because that's overzealous science, carrying in it the determination of die-hard reductionist intent on slapping down as many old wives tales as possible, even if the tale in question just happens to be your own, informative state of feeling so elegantly evolved to serve by hashing down infinite variables into a single, readable state.
 

Cream Gravy?

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Hmm yeah bad example, we don't have clear consensus on the meaning of holing. I myself would take being able to attend to bathroom business as a clear sign I'm not holing, but I suppose YMMV.
Fair enough, I never really exceeded doses of 80mg over a night with MXE. Some go much further. Perhaps I never truly holed.

I found it very incapacitating and pleasant in the body nonetheless, almost like a more psychedelic opioid.
 
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