Dissociatives Ketamine Cramps

[Esperighanto]

Is the damage from ingestion or just from it being in your blood? So the administration method doesn’t change the amount of damage it’s doing?

Backing up @LucidSDreamr I've been around many people who strictly use ketamine IM and they're always the worst off with damage accumulated, insufflating small amounts of ketamine infrequently appears to be the best. No more than a 300mg dose every other week seems to be a healthier range than excessive dosing or frequency. Studies on mice that use or IV administration are also the worst as far as toxicity.

Arylcyclohexylamines overall seem to exhibit toxicity relative to both dose and frequency, but the dose of stronger arylcyclohexylamines is lower for equivalent effects, right? As such, the idea is that a lower amount of a more potent arylcyclohexylamine reaching the same effect may exhibit lower toxicity. I can't find a single academic source that says that, but it's the "street lore" on the matter worth taking with a fistful of salt.

 

[pnillyg]

Yea my body’s not happy from the ketamine. Have to stop now and let it re-generate so have to find something to replace it for now…

 

[tryptakid]

Ingestion method doesnt matter.

Actually I think it makes a difference. IV/IM use are less likely to cause issues than intranasal. This may be related to ketamine that ends up in the stomach after ingestion when snorted, but not after injection (though I'll admit that I don't know how metabolism of drugs given IM/IV after they take effect so perhaps they wouldn't make a difference here. I've just heard that IN ketamine is more damaging.

I’d do dope if I had a safe supply but can only get bupe… I guess bupe or kratom is sounding like my only options besides benzos. Damn why do the best things have to be so damaging. Thank you for sharing those experiences/writing. I really just need something and I’m still trying to find what works. I guess adderall does too but the comedowns are brutal. Oy vey

PCP and the 3-substituted PCx drugs are too potent to require ingestion at the levels that would cause bladder issues. As a result, they can be used without the same issues. They aren't without risk of course, but if this is a major concern then you could consider them.

Additionally - I've been using Ketamine since 1999. I've gone through phases of sporadic high dose use, and semi-consistent low dose use. I usually take total abstinence breaks after using for a month or two. I also have a pretty high permatolerance and require much higher dosing than many people (though admittedly this is because many people I know in person don't have as much experience with ketamine. I have had no major issues from ketamine use other than an occasional increase in frequency of urination when using.

I will also say that I am someone who consistently drinks low doses of sugar throughout the day (typically ginger ale mixed with kombucha and seltzer water) and I strongly believe that increasing hydration when using and prioritizing electrolyte maintenance may be highly effective at preventing bladder issues from ketamine. I believe that ketamine causes urine to become caustic to the bladder, and have noted that ketamine causes me to feel more dehydrated when compared to the same level of activity while abstinent. As a result, I make sure to push fluids while using (gatorade would be a very simple way to do this). My hunch is that low urine volume from dehydration plus an increase in causticicity related to the arcyclohexamine leftover in the urine is what causes these issues as others have noted, and I believe that ketamine's activity as a sodium channel blocker may impact human fluid retention while using. Thus, hydration with increased electrolyte consumption may help. Further, I would not be surprised if the increased sugar from things like ginger ale or gatorade may balance some of the causticity as well.

Sugar is also a fairly effective home remedy for a bad k-hole. It's old raver wisdom and I've found it helpful when needing to regain composure in the past. I do wonder if their may be some relationship to this as well.

 

[pnillyg]

Thanks for the insights! super interesting. I’ve been using it for 3 months daily and my tolorence has gotten incredibly high (300mg 3 x daily) and I get what I used to get from 12.5-25mg. All sublingual by the way. Yesterday I took down 1500ml of iv bags in the time my buddy took down 500ml. I needed it been waking up super dehydrated and recently noticed the need to urinate more frequently followed by pink urine yesterday so in the off chance that’s not from the IV it could be blood. Need to let my body heal I believe. I just wish it wasn’t so toxic because it’s helped me in more ways than one and has proven the most mentally beneficial medication I’ve used.

 

[LucidSDreamr]

Actually I think it makes a difference. IV/IM use are less likely to cause issues than intranasal. This may be related to ketamine that ends up in the stomach after ingestion when snorted, but not after injection (though I'll admit that I don't know how metabolism of drugs given IM/IV after they take effect so perhaps they wouldn't make a difference here. I've just heard that IN ketamine is more damaging.


PCP and the 3-substituted PCx drugs are too potent to require ingestion at the levels that would cause bladder issues. As a result, they can be used without the same issues. They aren't without risk of course, but if this is a major concern then you could consider them.

Additionally - I've been using Ketamine since 1999. I've gone through phases of sporadic high dose use, and semi-consistent low dose use. I usually take total abstinence breaks after using for a month or two. I also have a pretty high permatolerance and require much higher dosing than many people (though admittedly this is because many people I know in person don't have as much experience with ketamine. I have had no major issues from ketamine use other than an occasional increase in frequency of urination when using.

I will also say that I am someone who consistently drinks low doses of sugar throughout the day (typically ginger ale mixed with kombucha and seltzer water) and I strongly believe that increasing hydration when using and prioritizing electrolyte maintenance may be highly effective at preventing bladder issues from ketamine. I believe that ketamine causes urine to become caustic to the bladder, and have noted that ketamine causes me to feel more dehydrated when compared to the same level of activity while abstinent. As a result, I make sure to push fluids while using (gatorade would be a very simple way to do this). My hunch is that low urine volume from dehydration plus an increase in causticicity related to the arcyclohexamine leftover in the urine is what causes these issues as others have noted, and I believe that ketamine's activity as a sodium channel blocker may impact human fluid retention while using. Thus, hydration with increased electrolyte consumption may help. Further, I would not be surprised if the increased sugar from things like ginger ale or gatorade may balance some of the causticity as well.

Sugar is also a fairly effective home remedy for a bad k-hole. It's old raver wisdom and I've found it helpful when needing to regain composure in the past. I do wonder if there may be some relationship to this as well.

Based on my understanding of the mechanism of damage, which is not certain, I think IV IM would be the worst because of the higher BA.

 

[tryptakid]

Thanks for the insights! super interesting. I’ve been using it for 3 months daily and my tolorence has gotten incredibly high (300mg 3 x daily) and I get what I used to get from 12.5-25mg. All sublingual by the way. Yesterday I took down 1500ml of iv bags in the time my buddy took down 500ml. I needed it been waking up super dehydrated and recently noticed the need to urinate more frequently followed by pink urine yesterday so in the off chance that’s not from the IV it could be blood. Need to let my body heal I believe. I just wish it wasn’t so toxic because it’s helped me in more ways than one and has proven the most mentally beneficial medication I’ve used.

I'd highly urge you to start consuming increased electrolytes and overall increased hydration. I would also urge you to lower your overall dose - 300mg x3/day over several months is definitely getting you much closer to the amounts needed to see damage.

One of the benefits of IM injection is that it's bioavailability is much greater, and thus you need far less than nasal or buccal requires for a greater effect. I find that IM rarely runs into the tolerance issues I bump into from other ROAs

 

[tryptakid]

Based on my understanding of the mechanism of damage, which is not certain, I think IV IM would be the worst because of the higher BA.

Better - you need a lower dose. The full dose goes into your system and is excreted from your system. Higher BA means you get more of an effect from lower doses.

For reference - he describes 300mg 3x/day for several months. That is much higher than my maximum dosing has ever been despite having used for over 25 years, at times using for months at a time consistently.

 

[pnillyg]

I'd highly urge you to start consuming increased electrolytes and overall increased hydration. I would also urge you to lower your overall dose - 300mg x3/day over several months is definitely getting you much closer to the amounts needed to see damage.

One of the benefits of IM injection is that it's bioavailability is much greater, and thus you need far less than nasal or buccal requires for a greater effect. I find that IM rarely runs into the tolerance issues I bump into from other ROAs

I’m stopping completely or at least dropping it to 300mg total I just recently relapsed on opiates and I started taking it to get off so no point in taking both now or I’ll be double screwed. May get back on kratom then use the ketamine again in a few weeks to get off or just CT and use the jet sparingly. Unfortunately I’m not familiar with IM dosages and I can get crystals for intranasal but don’t have any experience with needles besides using NAD subcutaneously. I’ll have to look further into the IM and IV doses just don’t have a “pure” or prescription product for injection.

 

[pnillyg]

Better - you need a lower dose. The full dose goes into your system and is excreted from your system. Higher BA means you get more of an effect from lower doses.

For reference - he describes 300mg 3x/day for several months. That is much higher than my maximum dosing has ever been despite having used for over 25 years, at times using for months at a time consistently.

Mine are troches for sublingual administration by the way not sure if I mentioned

 

[pnillyg]

Wonder if there’s a way to convert the troches to a liquid as they dissolve in warm water but have flavoring and fillers etc.

 

[pnillyg]

I'd highly urge you to start consuming increased electrolytes and overall increased hydration. I would also urge you to lower your overall dose - 300mg x3/day over several months is definitely getting you much closer to the amounts needed to see damage.

One of the benefits of IM injection is that it's bioavailability is much greater, and thus you need far less than nasal or buccal requires for a greater effect. I find that IM rarely runs into the tolerance issues I bump into from other ROAs

I do indeed drink 1-2hydration packs with water daily on top of the gallon or so I consume. Sometimes more

 

[tryptakid]

I do indeed drink 1-2hydration packs with water daily on top of the gallon or so I consume. Sometimes more

Aye - I imagine there's probably a level at which you lose the ability to compensate for the dehydrating effects of the drug itself, and my hunch would be that troches are a recipe for that given how much higher the doses tend to be.

My suggestion is to see about taking a tolerance break and then finding out whether you could restart at a lower dose via Spravato. Honestly, it's pretty easy to make a ketamine nasal spray - it's inherently antimicrobial which makes it relatively stable even in just distilled water and (I use) a small amount of ethanol.

Ketamine is able to be dissolved in up to 200mg/ml of water, so you can cap a nasal spray at 20mg/spray (as there are 10 sprays per ml.

If you can't get spravato, illicit ketamine is pretty easy to source. You can purchase a nasal spray bottle on amazon or direct from retailers like Snoos (I believ is the brand name). I've made my own sprays for a few years now and would be happy to help if you had any questions (other than sourcing of ketamine, of course) - though I've basically just outlined the process..

 

[tryptakid]

Wonder if there’s a way to convert the troches to a liquid as they dissolve in warm water but have flavoring and fillers etc.

Maybe but I imagine it would be more difficult than its worth. Can they give you a different formulation?

 

[LucidSDreamr]

Better - you need a lower dose. The full dose goes into your system and is excreted from your system. Higher BA means you get more of an effect from lower doses.

For reference - he describes 300mg 3x/day for several months. That is much higher than my maximum dosing has ever been despite having used for over 25 years, at times using for months at a time consistently.

Not if you beleieve it’s caused by an immunological response downstream of the initial pharmacological effect and not the mass of drug being put into the body.

200 mg IV has a stronger effect and downstream consequences than 200 mg nasal where the full dose isn’t active. So 200 IV would be worse than 200 nasal because more is absorbed IV and has a stronger and more damaging effect.

There is no science that I’m aware of that says bladder cystitis is caused by the chemical or metabolite acting directly with the bladder like is beleieved by drug users.

 

[tryptakid]

Not if you beleieve it’s caused by an immunological response downstream of the initial pharmacological effect and not the mass of drug being put into the body.

200 mg IV has a stronger effect and downstream consequences than 200 mg nasal where the full dose isn’t active. So 200 IV would be worse than 200 nasal because more is absorbed IV and has a stronger and more damaging effect.

There is no science that I’m aware of that says bladder cystitis is caused by the chemical or metabolite acting directly with the bladder

From what I understand - it is a problem that can occur across all arcyclohexamines (not all dissos) as long as there's a high enough concentration of metabolites in urine that contain an arcyclohexamine backbone (with everything from Ketamine to MXE to PCP and beyond do have). Ketamine bladder is particularly notable because ketamine requires a much higher dose to have an impact, especially when used regularly, compared to MXE and some of the other analogues with a similar potency. Since PCP is dosed at a much much smaller dose due to it's potency and duration of action, there has never been any major occurences of this issue even in heavy PCP users as the metabolic concentration just doesn't ever reach the same level as it does when you're using 100s of times the same dose, and that dose is much shorter acting.

If it is a downstream immune response, it wouldn't contrast with what I'm saying. The loading dose of something like CoVID resulted in much different disease effects when looking at how cases impacted people across the population. While the OG covid virus was pretty lethal, this was likely related to strain and lack of any recent immunity to coronvirii. The people who were mainly killed at higher rates than others were: The eldery, and those in poor health due to various things like weight, chronic diseases etc. The other group that saw an outsized death rate was medical persone working with acute covid infections early on, many who were young and in good health without the same complications. The most widely accepted explanation for this is one that I actually observed pretty early on in the pandemic - dose exposure had a major impact on disease effect when contracted. If you caught it in a fairly well ventilated place ( like a grocery store) without spending much time in direct contact with whoever infected you, you were likely to get only a mild infection.

However, if you were exposed to a very high dose in places with minimal ventilation and without adequate PPE or with PPE that was compromised for some reason (as happened to many who were working in these situations for hours on end, day after day), there was a much greater chance of severe infection up to an including death, and long term neurological sequelae which have resulted in long term disability for some of those folks.

That's sort of how I think about the ketamine bladder issue: it's the dose that makes the poison.

 

[LucidSDreamr]

From what I understand - it is a problem that can occur across all arcyclohexamines (not all dissos) as long as there's a high enough concentration of metabolites in urine that contain an arcyclohexamine backbone (with everything from Ketamine to MXE to PCP and beyond do have). Ketamine bladder is particularly notable because ketamine requires a much higher dose to have an impact, especially when used regularly, compared to MXE and some of the other analogues with a similar potency. Since PCP is dosed at a much much smaller dose due to it's potency and duration of action, there has never been any major occurences of this issue even in heavy PCP users as the metabolic concentration just doesn't ever reach the same level as it does when you're using 100s of times the same dose, and that dose is much shorter acting.

If it is a downstream immune response, it wouldn't contrast with what I'm saying. The loading dose of something like CoVID resulted in much different disease effects when looking at how cases impacted people across the population. While the OG covid virus was pretty lethal, this was likely related to strain and lack of any recent immunity to coronvirii. The people who were mainly killed at higher rates than others were: The eldery, and those in poor health due to various things like weight, chronic diseases etc. The other group that saw an outsized death rate was medical persone working with acute covid infections early on, many who were young and in good health without the same complications. The most widely accepted explanation for this is one that I actually observed pretty early on in the pandemic - dose exposure had a major impact on disease effect when contracted. If you caught it in a fairly well ventilated place ( like a grocery store) without spending much time in direct contact with whoever infected you, you were likely to get only a mild infection.

However, if you were exposed to a very high dose in places with minimal ventilation and without adequate PPE or with PPE that was compromised for some reason (as happened to many who were working in these situations for hours on end, day after day), there was a much greater chance of severe infection up to an including death, and long term neurological sequelae which have resulted in long term disability for some of those folks.

That's sort of how I think about the ketamine bladder issue: it's the dose that makes the poison.

There’s no evidence that the more potent arylcyclohexylamines are easier on the bladder just because less mass is ingested for the same intensity of effect.

Anecdotally I found ketamine to be far less irritating to the bladder even in higher mass vs DCK and MXE

 

[LucidSDreamr]

From what I understand - it is a problem that can occur across all arcyclohexamines (not all dissos) as long as there's a high enough concentration of metabolites in urine that contain an arcyclohexamine backbone (

I’ve never seen any science evidencing this despite it being widely believed by the drug using community. Not sure where this theory came from.

 

[tryptakid]

There’s no evidence that the more potent arylcyclohexylamines are easier on the bladder just because less mass is ingested for the same intensity of effect.

Anecdotally I found ketamine to be far less irritating to the bladder even in higher mass vs DCK and MXE

The only evidence I can suggest is based on the following - I just know what has worked for me as a long term user of ketamine, and what I've observed as someone who works in the medical field for many years specifically working with drugs users, while also following this phenomena since it began to emerge. As I'm no topic matter expert on medical pathology, though am probably more versed than most lay people, I can't speak with full expertise on the matter and I suggest these things in hope that someone could explore them more scientifically:

There seems to be more of a likelihood for full on bladder issues from ketamine specifically than from others - this may be simply a product of ketamine being much more commonly used, though MXE was pretty popular for a decade, and may have been used by people who weren't normally users of ketamine.

There hasn't been any indication I've seen in the literature of bladder issues prior to the mid 2000s, many decades after PCP emerged for use recreationally, with no indication that chronic users of PCP have had any health issues in this particular way

Ketamine bladder as a phenomena also seemed to not be an issue in the 90s, seeming to become more well known in the mid 00s, particularly in the UK due to a high concentration of chronic use as a street drug (in the way heroin and cocaine are used amongst lower socioeconomic status users which can impact the way they're used by those members) - ketamine was fairly rare in the US as supply began to dry up around 2000/2001 due to its scheduling in August of 99, and ketaset (american pharma k) being the primary form of it on the street until supplies dried up. It became less popular and opioids became far more popular amongst young drug users who had been the most robust users of ketamine during its heyday in the rave scene. There was even speculation that the bladder effects could be linked to something in the illicit manufacture of the drug as reports were unheard of during it's grey market use. My guess is that this was more related to a lack of tolerance and a relatively small population of users.

Ketamine bladder seems to be more prevalent in the EU, though I only base this on anecdotal information. It does seem that harm reduction campaigns were effective in reducing high dose use in the late 00s, after a series of severe cases resulted in some shitty outcomes, and notable discussion in the media and online..

Frankly, I don't know the specific chemical properties of DCK vs. MXE vs. Ketamine insofar as what would relate to irritability. My hunch is that there is a combination of effects happening with both the chemical metabolites present in the urine, as well as something currently unstudied related to the mechanism of action where sodium channels are disrupted which I speculate could increase vulnerability to organic damage when concentration and level of caustisity become elevated enough in vivo.

 

[LucidSDreamr]

The only evidence I can suggest is based on the following - I just know what has worked for me as a long term user of ketamine, and what I've observed as someone who works in the medical field for many years specifically working with drugs users, while also following this phenomena since it began to emerge. As I'm no topic matter expert on medical pathology, though am probably more versed than most lay people, I can't speak with full expertise on the matter and I suggest these things in hope that someone could explore them more scientifically:

There seems to be more of a likelihood for full on bladder issues from ketamine specifically than from others - this may be simply a product of ketamine being much more commonly used, though MXE was pretty popular for a decade, and may have been used by people who weren't normally users of ketamine.

There hasn't been any indication I've seen in the literature of bladder issues prior to the mid 2000s, many decades after PCP emerged for use recreationally, with no indication that chronic users of PCP have had any health issues in this particular way

Ketamine bladder as a phenomena also seemed to not be an issue in the 90s, seeming to become more well known in the mid 00s, particularly in the UK due to a high concentration of chronic use as a street drug (in the way heroin and cocaine are used amongst lower socioeconomic status users which can impact the way they're used by those members) - ketamine was fairly rare in the US as supply began to dry up around 2000/2001 due to its scheduling in August of 99, and ketaset (american pharma k) being the primary form of it on the street until supplies dried up. It became less popular and opioids became far more popular amongst young drug users who had been the most robust users of ketamine during its heyday in the rave scene. There was even speculation that the bladder effects could be linked to something in the illicit manufacture of the drug as reports were unheard of during it's grey market use. My guess is that this was more related to a lack of tolerance and a relatively small population of users.

Ketamine bladder seems to be more prevalent in the EU, though I only base this on anecdotal information. It does seem that harm reduction campaigns were effective in reducing high dose use in the late 00s, after a series of severe cases resulted in some shitty outcomes, and notable discussion in the media and online..

Frankly, I don't know the specific chemical properties of DCK vs. MXE vs. Ketamine insofar as what would relate to irritability. My hunch is that there is a combination of effects happening with both the chemical metabolites present in the urine, as well as something currently unstudied related to the mechanism of action where sodium channels are disrupted which I speculate could increase vulnerability to organic damage when concentration and level of caustisity become elevated enough in vivo.

I don’t think anecdotes really mean anything. The mechanism is not known according the citation at the end of this post but possible pathophysiological mechanisms of KC, including activation of inflammatory cells [21], dysfunction of bladder-urothelial barrier [22], dysregulation of neurotransmission [23], cell apoptosis [24,25], and oxidative stress [26,27],


To prove your hypothesis that it is caused by direct interaction of ketamine with the bladder there is some research but all of the citations above suggest other mechanisms Ketamine and its metabolites can affect urothelial cells by direct toxic damage on the bladder of KC, which was first reported in 2007 [10]. “As ketamine and norketamine, a metabolite of ketamine, are excreted from the kidney and retained in the urinary bladder, they can interact with the bladder urothelium and induce an inflammatory reaction [28].”

Seems to be much more complex than just ketamine interacting with the bladder wall and there’s several other sugged mechanisms https://www.mdpi.com/2079-7737/11/4/502

 

[tryptakid]

I don’t think anecdotes really mean anything. The mechanism is not known according the citation at the end of this post but possible pathophysiological mechanisms of KC, including activation of inflammatory cells [21], dysfunction of bladder-urothelial barrier [22], dysregulation of neurotransmission [23], cell apoptosis [24,25], and oxidative stress [26,27],


To prove your hypothesis that it is caused by direct interaction of ketamine with the bladder there is some research but all of the citations above suggest other mechanisms Ketamine and its metabolites can affect urothelial cells by direct toxic damage on the bladder of KC, which was first reported in 2007 [10]. “As ketamine and norketamine, a metabolite of ketamine, are excreted from the kidney and retained in the urinary bladder, they can interact with the bladder urothelium and induce an inflammatory reaction [28].”

Seems to be much more complex than just ketamine interacting with the bladder wall and there’s several other sugged mechanisms https://www.mdpi.com/2079-7737/11/4/502

If it's ketamine and norketamine, then why does MXE cause irritation if it's metabolites are N-Desethyl MXE and O-desmethyl MXE, without any ketamine or norketamine indicated? This, to me, supports the observation that this a larger issue related to arcyclohexamines as a whole, and would also warrant further analysis into the resulting structure of arcyclohexamine metabolites that are excreted and how variations may increase/decrease effect.



At the end of the day, this isn't super well understood as it's a relatively new issue with a relatively small effect size on the whole. While I could absolutely see the stuff you're listing from the research as also being plausible, I can't not include my own experiences with regards to what I have found helpful/protective, and where my understanding of how it's been helpful comes from. I'm the first to admit i'm not a scientist and while I have a pretty expansive understanding of drugs, I start to run into challenges once we're moving past the brain and nervous system and into the realm of psychology and behavior which is where I actually am an expert. Metabolism and excretion I am much less well versed in, and, I appreciate you sharing the citation as it's helpful to consider as part of this discussion.