Amygdala connectivity predicts ketamine treatment response
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The amygdala is, as is generally known, strongly associated with fear responses, or other negative emotional responses. The subgenual cingulate cortex has been associated with emotion regulation (e.g. down-regulating responses to negative stimuli). I believe that other treatment-prediction studies have found that connectivity between the subgenual cingulate and other brain regions like the amygdala predict treatment responses, so, their result is pretty consistent with the literature as far as I understand.
1. https://scholar.google.com/citations?user=bSXKfxkAAAAJ&hl=en...
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 certain amount of (ab)use.
Can we be sure that a similar thing won't happen with ketamine?
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 be wrong about that; webmd says, "For treatment-resistant depression, patients usually get the nasal spray twice a week for 1 to 4 weeks; then once a week for weeks 5 to 9; and then once every week or 2 after that." However, the use-cases I know about (from talking to researchers studying it) is as an intervention to prevent suicide during severe depression (since it's relatively fast acting).
As always, its a cost-benefit calculation, that should be carefully made in consultation with a professional. The cost of severe depression can be quite high.
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).
There is a long-term trial now in its 4th year with esketamine (https://clinicaltrials.gov/ct2/show/NCT02782104). I'm not sure how much has been published yet, but early data I saw supported immediate relief and long term benefit over the 4 years.
In terms of it being a sinister ploy by pharma, it's definitely priced higher than its ketamine generic counterpart, but for the vast majority of our patients, ketamine treatment out of pocket (since its not covered by insurance) is absolutely unaffordable, and pursuing the insurer-covered version of treatment is a high-value option.
A lack of physical dependence should not be interpreted as addiction-proof. Nobody is physically dependent on gambling, for example, but gambling addiction is prevalent.
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 neurotransmittor reuptake inhibitors have quite substantial problems associated with them too (there we arguably really have had a case of the mistaken and excessive wonder-drug status you allude to).
The true excitement of ketamine-based depression treatment is perhaps more in that it is something different. It quickly affects the problematic state, by some mechanism which appears to be quite different from the now "classical" antidepressants. That has potential both as a basis for more refined drugs and more importantly to better understand the real mechanisms underpinning depression.
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 commonly used in outpatient medical settings.
Ketamine is in a completely different category of drugs from cocaine and novocaine, which are also totally different from opiates.
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.
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.
"Opiates are dangerous and they are anesthetics; therefore ketamine is dangerous because it's an anesthetic" is, literally, a textbook logical fallacy.
If you'd like to argue that ketamine is dangerous based on some other reasoning, go ahead, but that doesn't change the fact that OP's logic is prima facie fallacious.
> Ever met an nmda receptor agonist addict?
I used to work in drug counseling, so, yes.
Except that I never made that exact argument. Textbook strawman fallacy.
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.
Ketamime has already been widely used for decades, in much larger doses than whats being discussed. We're not talking "short-term" here.
> 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.
Even that is a misrepresentation of the history of heroin. I guess it could appear that way if you take the Bayers advertising materials at face value (but hopefully you're not doing that). The dangers of opiates - and of morphine derivatives specifically - were well established by the time heroin was released.
I have tried ketamine for my PTSD and hasn't worked but stellate gangelion block worked perfectly after just one session .
I googled the procedure and it seems like it's an injection of "anesthetic" to a nerve in the neck. Is that what you're talking about?
I did it about 3 months ago I can't recall exactly.
I was able to find a head and neck doctor that agreed to do it and did it for about 800$.
60 minutes made an episode about it that's when I first knew I had to try it
There are 3 sites that they generally target but I just did right C6 .
If it does then ya for sure
Seems like we are.
https://scholar.google.com/scholar?start=10&q=methoxetamine+...
There is zero clinical evidence of bladder damage due to ketamine in the amounts used for clinical purposes.
Yes, there is evidence for bladder damage in heavy, chronic users, but none of that has been shown in therapeutic schedules, and there is very strong evidence against the existence of any such link in therapeutic schedules.
One promising rat study from 2015 shows that EGCG (epigallocatechin gallate) extracted from green tea has a protective effect on the bladder, reversing ketamine-induced damage to control levels. If you are taking ketamine for major depression or recreationally, taking EGCG before may prevent long-term bladder damage.
Summary from the study:
> "Objective
To investigate the protective effect of green tea epigallocatechin gallate (EGCG) on long-term ketamine-induced ulcerative cystitis (KIC) using a ketamine addiction rat model.
Materials and methods
Thirty Sprague-Dawley rats were divided into three groups which received saline, ketamine (25 mg/kg/d), or ketamine combined with EGCG (10 μM/kg) for a period of 28 days. In each group, cystometry and a metabolic cage micturition pattern study were performed weekly. Masson's trichrome study was done to evaluate the morphologic changes. Western blot analyses were carried out to examine the expressions of inflammatory protein [transforming growth factor-β (TGF-β)] and fibrosis proteins (fibronectin and type I collagen) in bladder tissues.
Results
Chronic ketamine treatment resulted in bladder hyperactivity with a significant increase in micturition frequency and a decrease in bladder compliance. These alterations in micturition pattern were accompanied by increases in the expressions of inflammatory and fibrosis markers, TGF-β, fibronectin, and type I collagen after long-term ketamine treatment. Masson's trichrome stain showed that ketamine treatment decreased urothelium thickness while increasing the collagen to smooth muscle ratio and exacerbating interstitial fibrosis. By contrast, simultaneous EGCG and ketamine treatment reversed ketamine-induced damage to almost control levels, showing the protective effect of EGCG.
Conclusion
This protective effect of EGCG may come from its antiinflammatory and antifibrotic properties."
[^1]: https://www.sciencedirect.com/science/article/pii/S187952261...
You'd have to stretch the definition of "occasional" to make this statement supportable. Clinical studies on the topic focus on chronic heavy users, whose usage far surpasses the dosing used by the median recreational user and typically persists for years. (In fact, most studies focus on recreational users who are using near-clinical levels, which is an order of magnitude more than the typical recreational dose, and doing so with regularity).
While it's possible that occasional use can cause issues, it's far from established fact, and the widespread usage of large doses of ketamine in inpatient settings for decades without reports of issues for those users would actually suggest otherwise.
Is that so? For ambien it's the opposite, usually the recreational dosage can be a lot higher for some users than a clinical dosage (5 or 10mg)
Correct. What you are saying is true for almost all drugs: recreational doses are typically higher than clinical doses. Ketamine is the exception.
The recreational dose for a ketamine-naive user[0] is somewhere between 5-20mg. The clinical dose for depression is 86mg (not a typo), which is sometimes doubled, and the clinical dose for anesthetic purposes (which is what ketamine is mostly used for) is between 500mg-1g. The latter is IM injection, so it's also much more bioavailable than the first two (ie, the effective dose differential is even higher).
Of course, regular users develop a tolerance and heavy chronic users of ketamine can do more. But that's due to tolerance, not representative of the typical baseline recreational dose. (If they were to need ketamine for inpatient anesthetia, they would need absolutely massive doses for it to be effective).
It's hard to overstate how unusual ketamine is in this regard! It's very difficult to find an example of another drug that is frequently used both recreationally and clinically (by different groups of people) for which the standard clinical dose is 10x the standard recreational dose.
[0] "naive" is not a judgmental term; it's the clinical term used to describe a user who has no prior experience with the drug, or who has no baseline tolerance (ie, whose prior usage is far enough in the past that it is no longer relevant).
To clarify: my understanding is that ketamine acts as a dissociative hallucinogen at lower doses and an anaesthetic at higher doses, so taking a higher dose will just knock someone out instead of giving them the dissociative/hallucinogenic effects.
> The clinical dose for depression is 86mg (not a typo), which is sometimes doubled, and the clinical dose for anesthetic purposes (which is what ketamine is mostly used for) is between 500mg-1g. The latter is IM injection, so it's also much more bioavailable than the first two (ie, the effective dose differential is even higher).
Ketamine is normally dosed based on body weight[0]. For depression IV, the dose is 0.1–0.75mg/kg/40mins, most commonly 0.5mg/kg/40mins. Clinical use in IM seems to be less consistent, with some clinicians using the same range and others doubling it, so the 86mg could be used for a wide range of body weights.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023575/table/T...
[1] https://www.psychiatrist.com/jcp/depression/ketamine-for-dep...
If we're being specific, the FDA-approved treatment of ketamine for depression is a fixed 84mg dose. It is not adjusted for body weight.
(I did invite irony by saying that it wasn't a typo - it's 84 and 56 for redoing, not 86 and 54).
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.
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
It allows you to take a much lower dose of dextromethorphan and so have fewer undesirable side effects. It helped me cope with some chronic physical pain I was suffering with at the time (in addition to depression).
This is insane gouging, as you could literally make it yourself by getting a prescription for generic bupoprion and some store-bought cough medicine.