Studies about ketamine have been rolling in over the past few years. Some important notes:
1. Almost all of these are looking at IV ketamine at very low doses (lower than anestheic or "recreational" dosing).
2. Like most of these trials, this is also a small trial (18 patients).
3. This was an adjunctive therapy, for patients who were on stable dosing of lithium or valproic acid which are first line for bipolar disorder.
Cool stuff, but preliminary at this point. Hopefully it will lead to options that are safer, more convenient, and with less abuse potential but maintain the rapid response that appears to be related to glutamatergic activity.
Recreational ketamine use is almost all insufflated (snorted) or intramuscular (IM) injection, right? I'm not sure how different the effects would be for IM vs. IV, except maybe a slightly faster onset and higher peak.
The "rule of halves" for different forms of drugs (pill vs. mucous membrane/sublingual vs. insufflated vs. smoked vs. injected) is interesting, but I'm not sure where IM vs. IV falls.
Insufflated it takes about ten minutes to come on. It is extremely overwhelming - not necessarily in a bad way. Disassociates are by far the weirded class of drugs.
I've witnessed enough weird ketamine trips to hope nobody close bothers with it again.
It's too sketchy and has a wide variety of effects on people, depending on your brain chemistry. It can produce sedation, or very fast anti-depressant effects, and/or other unusual body responses [1].
Whereas I think it is dramatically underused -- it's a great battlefield or improvised conditions anaesthetic, since it doesn't depress respiration very much. All of the psychiatric features are minor compared to being able to do surgery quickly and not kill the patient.
YMMV; Annecdotes != data; correlation != causation etc.
but I've known a lot of modest, moderate and heavy recreational ket users - It's been quite a popular recreational drug in the UK for about 15 years. I would perceive (being not a doctor or anything useful) that the proportion of them which are depressed in some way is a noticeably higher than the rest of the people I've ever met.
It's an addictive drug (perhaps not physically, but definitely behaviourally/psychologically). In my opinion it grossly interferes with peoples' ability to interact with those who don't partake. I find it difficult to recall a single example of its use improving someone's well-being - the converse in fact.
Anyway, just adding my observations/bit of life experience.
Heroin also improves depression within minutes. Ketamine is even more dangerous, and may cause severe cognitive difficulties with long-term use like other NMDA antagonists like ethanol and the benzodiazapenes (which, it should be noted, actually worsen depression in the long run).
You are touching on some legitimate reasons for skepticism, however I think it's a bit more complicated than you are suggesting. Clinically, the response to alcohol, benzos, and heroin on mood is reported less as improvement than making the symptoms easier to ignore. I'd be surprised to see those agents prompt this kind of change on the MADRS. Plus alcohol and benzos act primarily through GABA, and heroin via mu opioid receptors, so the mechanisms are not totally comparable.
The long-term effect of ketamine is not yet understood, but establishing safety and effectiveness in these very small trials is the first step.
ketamine is being studied as single (for depression) or occasional (two week interval in the case of this study) dose, at which frequency there are no known deleterious effects. if you have evidence to the contrary, let's see it.
- The full methodology isn't actually published anywhere.
- The rankings are creating by combining a lot of different factors that don't have anything to do with each other, e.g. by combining harm to the user with harm to society. This means that drugs like coffee end up being more dangerous than drugs like heroin, simply because more people use coffee than heroin so the total social costs are greater.
- The harms for drugs are measured as they are typically used, rather than correcting for things like differences in demographic and route of administration. This leads to drugs like heroin looking more dangerous than they are, because people who have drug abuse problems tend to gravitate toward drugs like heroin. (Whereas people who use, say, Khat tend not to be the worst of the worst as drug abusers go.)
- The harms of the drugs caused by prohibition are not accounted for. (E.g. they are counting people using dirty needles and impure/unknown/fake drugs as being a harm that stems from heroin, but they aren't counting using dirty needles and fake Starbucks as being a harm that stems from drinking coffee.)
- They're not accounting for the benefits of drug use, only the harms.
I could keep going, but I think I've sufficiently proven my point and then some.
Maybe less dangerous in the immediate term from overdose, but isn't ketamine potentially rather dangerous to the brain? Wikipedia seems to suggest that frequent ketamine usage causes memory issues, and there might be possible brain damage.
Whereas opiates, to my knowledge, don't actually have any serious side effects, or long term health issues (apart from constipation and perhaps lowered testosterone). Apart from the overdose risk, that is.
Ketamine blocks the NMDA receptor, which is thought to be the receptor that causes memory formation. So it is expected to affect memory.
The brain damage effect is uncharacterized in humans. Several NMDA drugs cause this effect in rats, but none of them have been found to cause devastating problems in humans except PCP.
There is some suggestion that opioids cause cancer, but the only study was small and observational.
of an overinterpreted study. I wish the researchers well. Other thoughtful comments here have already pointed out issues such as the very small sample size and limited follow-up given to the patients.
> When the patients received ketamine, their depression symptoms significantly improved within 40 minutes, and remained improved over 3 days. Overall, 79% of the patients improved with ketamine, but 0% reported improvement when they received placebo.
So they only checked up on them for three days. Bipolar depression is generally chronically recurring. Sufferers will feel "better" for a short period of time, and then slip back into depressive mind-states.
This would be much more interesting if it was a longer-reaching study.
It is in a typical treatment group, but not all that strange in a treatment-resistant population who have specifically been selected because they haven't responded to other things.
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1. Almost all of these are looking at IV ketamine at very low doses (lower than anestheic or "recreational" dosing).
2. Like most of these trials, this is also a small trial (18 patients).
3. This was an adjunctive therapy, for patients who were on stable dosing of lithium or valproic acid which are first line for bipolar disorder.
Cool stuff, but preliminary at this point. Hopefully it will lead to options that are safer, more convenient, and with less abuse potential but maintain the rapid response that appears to be related to glutamatergic activity.