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Amygdala connectivity predicts ketamine treatment response

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Re: Amygdala connectivity predicts ketamine treatment response

#21

Post by cmrdporcupine »

pgt wrote: post #12

Most Ketamine users are unaware that even occasional usage can cause untreatable ulcerative cystitis, a.k.a. Ketamine Bladder Syndrome. Ketamine thins the urothelium while increasing the collagen to smooth muscle ratio and exacerbating interstitial fibrosis. The syndrome is untreatable and causes serious problems down the line. One promising rat study from 2015 shows that EGCG (epigallocatechin gallate) extracted fro…

Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine.

Re: Amygdala connectivity predicts ketamine treatment response

#22

Post by cmrdporcupine »

etiam wrote: post #9
bheadmaster wrote: post #7

Earlier quoted context omitted.

This sounds really promising, but one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). When heroin was first discovered, it was hailed as a wonder-drug, and it was also considered an effective treatment for severe depression. However, after some time, people realized that its addictive properties and high range of potential tolerance make it backfire pretty badly after a certa…

From what I've heard ketamine is already (ab)used as a recreational drug since decades back and does have addiction risk. Not addiction risk anything like heroin though, and the trips are apparently mostly unpleasant. Ketamine in its present form is decidedly not ideal for depression treatment, but probably a tradeoff often worth considering compared to the risks of severe and enduring depression. Amine neurotransmit…

Exactly. Ketamine as a "party drug" is more something taken "to get f*cked up" rather than "to feel good." I've always found it odd that it caught on as a party drug, TBH. It's likely more to do with availability.

Re: Amygdala connectivity predicts ketamine treatment response

#23

Post by chimeracoder »

cmrdporcupine wrote: post #21
pgt wrote: post #12

Most Ketamine users are unaware that even occasional usage can cause untreatable ulcerative cystitis, a.k.a. Ketamine Bladder Syndrome. Ketamine thins the urothelium while increasing the collagen to smooth muscle ratio and exacerbating interstitial fibrosis. The syndrome is untreatable and causes serious problems down the line. One promising rat study from 2015 shows that EGCG (epigallocatechin gallate) extracted fro…

Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine.

> Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine

The fact that they're both dissociatives doesn't mean they're substitutable in any given context.

Dextromethorphan is a much riskier drug overall than ketamine, in almost every measurable way. It's very easy to overdose on dextromethorphan, to the point where people routinely do it by accident while self-medicating for a cough. By contrast, it's actually quite difficult to overdose on ketamine - the LD50 is quite high, and a person would likely incapacitate themselves halfway through and be unable to finish.

They also have dramatically different effects - there are actually very few contexts in which both could be considered an acceptable choice for a given goal.

The bladder issues with ketamine are only documented for chronic heavy users. There's no clinical evidence of it for one-time use, and given the extensive use of ketamine in controlled settings for several decades, the absence of evidence is (in this case) strong evidence of absence.

Re: Amygdala connectivity predicts ketamine treatment response

#24

Post by cmrdporcupine »

chimeracoder wrote: post #23
cmrdporcupine wrote: post #21

Earlier quoted context omitted.

Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine.

> Thanks for bringing this up. It's super important. And also makes me why other drugs in this class (dissociatives) aren't being looked more aggressively. Dextromethorphan -- in common cough syrup -- is one example. It has other side effects (nausea, etc.) but doesn't have the bladder destructive issues associated with ketamine The fact that they're both dissociatives doesn't mean they're substitutable in any given…

Honestly, I'm speaking from personal experience with both drugs. When you're talking about overdose on dextromethorphan I think you're mischaracterizing. The LD50 of dextromethorpan is 150mg/kg in mice. A dissociative/psychedelic dose of dextromethorpan is 300-500mg in an average adult. A typical cough medicine is 15-30mg per dose, and a bottle usually has no more than 250mg or 300mg. Nobody is "accidentally" hitting a toxic dose. Overdosing really means: getting somewhat similar effects to ketamine -- along with a nasty dose of dizziness and nausea. To have an extremely serious reaction to dextromethorphan that is drastic, you'd have to consume multiple bottles of cough syrup.

On other hand I've been in, and had friends in, so-called "k-holes" because of doses of ketamine that were too high and the experience was ... awful. Imagine thinking you're dead, but you're still conscious.

Both are NMDA antagonists. Both provide emotional and physical dissociation. They are in the a similar class of experiences.

Psychotherapeutic doses of ketamine are not one-time. At least not from the reading I've been doing. They have been found to be more effective done over several sessions. I honestly worry about the potential for bladder damage because it has not been studied well and also this kind of treatment is something we're looking into for a loved one

Re: Amygdala connectivity predicts ketamine treatment response

#25

Post by engined »

jonnycomputer wrote: post #8
bheadmaster wrote: post #7

Earlier quoted context omitted.

This sounds really promising, but one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). When heroin was first discovered, it was hailed as a wonder-drug, and it was also considered an effective treatment for severe depression. However, after some time, people realized that its addictive properties and high range of potential tolerance make it backfire pretty badly after a certa…

Good question. Ketamine has been a party drug for quite a while now, and as far as I know, hasn't been shown to be particularly dependency-inducing, though low-dose ketamine over the long term might be ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236511/ ) Also, as far as I know, ketamine treatment isn't intended as an ongoing medication, like an SSRI, but as a treatment for acute episodes of depression. I might b…

The WebMD article is referencing esketamine, also known as Spravato, which is an FDA authorized form of ketamine. It's generally indicated for longer-term use in patients with Treatment Resistant Depression (TRD), and has really good results on par with ketamine (IV or intramuscular).

At Lumin Health, we treat about 80% of our patients with esketamine, and the rest with ketamine (generally only if they don't meet esketamine criteria). After the initial course, patients tend to find a good balance of ongoing care that helps treat their particular depression / depressive symptoms. This happens less with ketamine since it tends to be prohibitively expensive to continue care (upwards of $1k/month).

Re: Amygdala connectivity predicts ketamine treatment response

#26

Post by DontchaKnowit »

chimeracoder wrote: post #19
bheadmaster wrote: post #7

Earlier quoted context omitted.

This sounds really promising, but one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). When heroin was first discovered, it was hailed as a wonder-drug, and it was also considered an effective treatment for severe depression. However, after some time, people realized that its addictive properties and high range of potential tolerance make it backfire pretty badly after a certa…

> one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). The fact that two drugs both can be used as an anesthetic doesn't tell you very much besides that, especially when comparing across different drug classes. For example, cocaine and novocaine are both anesthetics that belong to the same drug class, and yet they have radically different risk profiles, despite both being comm…

I dont think its a fallacy. Its definitely a consideration. Ever met an nmda receptor agonist addict? its real shit. It aint pretty. And ive definitely seen it done as a sort of depression-relief-addiction. Had a close friend who I found out had been drinking like 2 or 3 bottles of cough syrup (over the counter, dextromethorphan) daily. She had a hell of a time kicking it. Idk if she ever did.

People on these type of drugs long term end up with severe memory issues, fogfy brained all the time, and if its ketamine add in a completely obliterated bladder.

I dont think this is an idea that can be dismissed trivially as a fallacy.

Re: Amygdala connectivity predicts ketamine treatment response

#27

Post by DontchaKnowit »

I dont understand why we arent looking into methoxetamine over ketamine. Or any of the derivatives with a stronger dose-response curve. DCK, O-PCE, etc. These all have similar chemical and psychoactive properties and the doses are orders of magnitude smaller ergo they dont completepy fuck your bladder up.

Re: Amygdala connectivity predicts ketamine treatment response

#28

Post by jonnycomputer »

engined wrote: post #25
jonnycomputer wrote: post #8

Earlier quoted context omitted.

Good question. Ketamine has been a party drug for quite a while now, and as far as I know, hasn't been shown to be particularly dependency-inducing, though low-dose ketamine over the long term might be ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236511/ ) Also, as far as I know, ketamine treatment isn't intended as an ongoing medication, like an SSRI, but as a treatment for acute episodes of depression. I might b…

The WebMD article is referencing esketamine, also known as Spravato, which is an FDA authorized form of ketamine. It's generally indicated for longer-term use in patients with Treatment Resistant Depression (TRD), and has really good results on par with ketamine (IV or intramuscular). At Lumin Health, we treat about 80% of our patients with esketamine, and the rest with ketamine (generally only if they don't meet esk…

Do appreciate informed commentary; thank you. I work in a research lab studying depression and the brain, but am not a clinician (which is why I threw in a lot of caveats).

Re: Amygdala connectivity predicts ketamine treatment response

#29

Post by jonnycomputer »

DontchaKnowit wrote: post #27

I dont understand why we arent looking into methoxetamine over ketamine. Or any of the derivatives with a stronger dose-response curve. DCK, O-PCE, etc. These all have similar chemical and psychoactive properties and the doses are orders of magnitude smaller ergo they dont completepy fuck your bladder up.

>I dont understand why we arent looking into methoxetamine over ketamine.

Seems like we are.

https://scholar.google.com/scholar?start=10&q=methoxetamine+...

Re: Amygdala connectivity predicts ketamine treatment response

#30

Post by bheadmaster »

chimeracoder wrote: post #19
bheadmaster wrote: post #7

Earlier quoted context omitted.

This sounds really promising, but one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). When heroin was first discovered, it was hailed as a wonder-drug, and it was also considered an effective treatment for severe depression. However, after some time, people realized that its addictive properties and high range of potential tolerance make it backfire pretty badly after a certa…

> one thing that worries me is that ketamine is a sort-of painkiller (dissociative anesthetic). The fact that two drugs both can be used as an anesthetic doesn't tell you very much besides that, especially when comparing across different drug classes. For example, cocaine and novocaine are both anesthetics that belong to the same drug class, and yet they have radically different risk profiles, despite both being comm…

> It's a fallacy to assume that ketamine would be subject to the same issues as opiates just because both happen to be usable as anesthetics.

Sure, but it's also a fallacy to assume that nothing bad can happen in the long-term just because it appears promising in the short-term. I wasn't saying it's gonna happen the same exact way as it did with heroin (of course it won't, it's not an opiate), I was just making an example of a drug that happened to appear benign and promising, but have serious unforeseen consequences in the long term.

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