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Ketamine and Depression: A Breakthrough? (discovermagazine.com)
86 points by DiabloD3 on May 7, 2016 | hide | past | favorite | 55 comments


Back in my raver days, when this was still doable, one of my boys started driving to Mexico and buying K there and bringing it back in cheap water bottles to get by the border DEA.

One day he shows up at the club and says, "hey, check out my car trunk" and was like "uhhh ok that's kinda weird" but I went out and presto, there was 4 one-liter water bottles full of ketamine.

Thats a shitload of K, considering a vial is 50ml and costs around $100. So I started selling it for him, and man did it go fast. Almost everyone loved it, including myself. Oddly enough, even people who did too much the first time and had a really wack k-hole experience would try it again.

It was rather miraculous to me, and surely did some sort of transformative rearranging of my brain while I was dosing it. I think what I remember best was that it became my self-described "drug of choice", which, honestly, was a pretty huge achievement in my life.

I liked it because it removed my desire to do other, much darker and destructive drugs somehow, and it wasn't just a matter of typical substitution, but something much more fundamental, so studies like this are very unsurprising to me, and I really hope these researchers keep at it.


I'm glad to hear you're alright. As I'm sure you know, dissociatives can be terribly addictive. I've watched friends with similar supplies (nowadays it comes in bulk powder from India) turn into the walking dead. That's not even to mention the permanent damage and having to urinate every 10 minutes.


Recreational use is large doses.

The studies I've seen for medical psychiatric use were about 5 mg per kg of body weight.


0.5 mg/kg. 5 mg/kg will be a hell of a ride.


Ah, yes. Max dose used in this study was 80 mg. http://www.oxfordhealth.nhs.uk/news/first-uk-study-of-ketami...

http://www.oxfordhealth.nhs.uk/service_description/ketamine-...

I don't know where I got 5 mg/kg from.


This article misses the second part of the study, as elucidated by Derek Lowe here http://blogs.sciencemag.org/pipeline/archives/2016/05/06/it-...:

In a rather elegant experiment, the authors deuterated ketamine at the methylene next to its carbonyl group, and showed that this compound (as expected) displayed the same NMDA activity as the parent compound – but that it was far slower at producing the metabolite, and had no activity in the antidepressant screens.


The "antidepressant screens" referred to here are in mice, not humans. The Nature paper is an amazing set of experiments that provide very compelling evidence that (2R,6R)-HNK is responsible for the antidepressant effects of ketamine in mouse models of depression, but Neuroskeptic is right that it's not clear that (2R,6R)-HNK is also responsible for the antidepressant effects of ketamine in humans. We know that mouse models of depression are not necessarily great; SSRIs seem to be more effective in mouse models than they are in humans.


Per Neuroskeptic's due diligence, human effects don't look promising.

>>> This is a citation to one of their own papers, from 2012. There’s just one problem – as far as I can see that paper didn’t find the correlation that Zanos et al. say it did.


Has there been any increase in illegal use of ketamine since research on its use as a depression treatment first started being published?

Having dealt with those issues for many years, and recovered, I can see a real danger in those who suffer from depression saying "K will fix this? I'll try anything". I would have.

I'm a firm believer in drug law reform and decriminalization of drug use but from what I've seen of it Ketamine isn't something you want people taking out of desperation, with little knowledge of how crazy it just might get. Or worse, developing a dependency on. It's pretty serious stuff.


I've used ketamine to self-medicate depression. I decided to out of desperation. It was extremely effective for me.

Several provisos for potential users:

- Read the papers. If you can't read the papers on K as a depression treatment and come up with your own dosing protocol, you probably shouldn't try K.

- Probably don't try it if you have an addictive personality.

- Make sure you're aware of potential side effects such as memory and urinary issues. That said, doses used in treatment protocols shouldn't come anywhere near that.

I waited forever to just get some goddamn K and treat myself, because everybody on the internet is like "don't do it, you'll fuck yourself up". I'm smart and do my homework, and I regret not trusting myself and suffering for longer than needed.


I wouldn't even know where to get it, and I don't want to get caught and go to jail, due to our stupid drug laws. :(


it's a schedule 3 drug, so a misdemeanor. i don't think you'd get any jail time if you got caught (assuming you're a first time offender in CA). if you're that desperate and you've read up on it and consider it a viable escape from that hell i know too well, give it a shot. (i have not used it).

shame i had to make a new account to speak freely about this.


No..in fact hell no.

Ketamine is schedule 1 or 2 I believe everywhere in the US, so that is definitely a felony.


It's Schedule III: https://en.m.wikipedia.org/wiki/Ketamine#Legal_status

"Ketamine is a "core" medicine in the World Health Organization's Essential Drugs List, a list of minimum medical needs for a basic healthcare system."


"...flunitrazepam, ketamine, or any other Schedule I or Schedule II CDS is a Class 6 felony."

http://www.criminaldefenselawyer.com/resources/criminal-defe...


Well, that's wrong.

"Schedule III drugs, substances, or chemicals are defined as drugs with a moderate to low potential for physical and psychological dependence. Schedule III drugs abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV. Some examples of Schedule III drugs are:

Products containing less than 90 milligrams of codeine per dosage unit (Tylenol with codeine), ketamine, anabolic steroids, testosterone"

http://www.dea.gov/druginfo/ds.shtml

https://www.erowid.org/ask/ask.php?ID=2972


Ok fair enough and a great link...but here is the twist to this.

That page describes Xanax as a schedule 4, and yet I have been charged not once but twice with felony possession of Alprazolam and was adjudicated guilty both times, so perhaps we are both correct in this case, and that yes its a schedule 3 but its also a felony.


The GP link is specific to Colorado.


The darknet is very straightforward to use and almost riskless for a small time buyer


Talk about a relevant piece of news: https://news.ycombinator.com/item?id=11652751

You probably already saw it on the front page, but I just thought that was an interesting coincidence.


The blog says that HNK (the purported antidepressant) is a known metabolite of ketamine, but then claims:

> However, getting regulatory approval for such a study, which would technically (as far as I know) be a first-in-man trial of HNK, might take a long time.

I don't understand this. We already know that when we give ketamine to patients they are exposed to HNK. Is there a real risk that it is more dangerous in isolation?

Even if caution is required in the first patients, why do we accept as normal that developing treatments like this should involve years of waiting for bureaucratic approval?


Disassociatives have been used for a while in the treatment of opiate addiction, including the usage of higher doses of dextromethorphan to treat heroin addicts. To me it comes with little surprise that this could also be an effective treatment for depression, despite the fact that depression isn't necessarily something that can just be treated away. I've personally done more than my fair share of recreational ketamine and it seemed to aid my coping with some major life issues I've had, though I suppose this could also be placebo. Regardless, I'm glad these types of studies are being done and hope to see some more concrete evidence of positive effect.


Ketamine is still far too drastic and probably only really necessary when the depression is acute and prolonged. I would rather advise a non-SSRI like tianeptine. At least that is currently O.C. without an Rx required.

Edit: looks like HN has been down this very same road before[0] when Ketamine was brought up; and I'm smiling to see that I'm not the only one to think of Tianeptine in contrast to the drastic use of Ketamine. Psychopharmacology is the tried and true drug pusher of our times.

[0]: https://news.ycombinator.com/item?id=4615750


Well, afaik antidepressant doses of ketamine seem to be lower than 100 mg - which is quite a bit less than the most drastic of recreational doses - I don't know (but would love to see research conducted on) whether that's actually that risky.

Tianeptine is a mu-opioid receptor agonist, so it has abuse & addiction potential above therapeutic doses. It's also rx-only in many countries, according to Wikipedia.

Additionally, ketamine works for a week whereas it's not uncommon for people who use tianeptine to split their daily regimen into something like 3 separate doses throughout the course of the day.

At least neither require several weeks to reach efficacy while initially potentially increasing the severity of depression...


> It's also rx-only in many countries, according to Wikipedia

Those countries include parts of Europe, Asia and Latin America.

On the same Wikipedia page, "not available [as in, at all, even with a prescription] in Australia, Canada, New Zealand, the U.K. or the U.S."

Kind of a bummer, I was starting to think I might have something new to look into. Not surprised, though.


You can order it online no problem in the U.S. I'm not gonna source anything for you b/c I don't want to seem like a shill or anything, but this type of info is easily acquired on r/nootropics - just use your common sense and ignore all the BS medical advice on that subreddit, lol.


Usually when a drug is not available in the us it means that no regulations address it at all, do its legal to import as long as you don't sell it domestically. Do your researvh, but this is what I hear from nootropics enthusiasts.


So this is what Nature has come to? Following up on a study where people took Ketamine once and felt good for a while? Nobody was doubting that people could get high on Ketamine. Isolating the most intoxicating metabolite is a bit useful, but it really bothered me that "studies" looking at a single dose of Ketamine and labeling the rather short effect "sustained" get so much press.


The Nature paper was about isolating a metabolite of ketamine that is not responsible for the intoxicating aspects, but is responsible for the antidepressant activities (at least in mice).


From my limited comprehension of the matter, what about:

http://jneuroinflammation.biomedcentral.com/articles/10.1186...


However, one of the nasty side effects of long term K use is having a tiny bladder.


Yes, but these newer therapeutic uses have much lower dosing than recreational use. Recreational users take doses of about a gram or more. These thereutic doses tend to be on the order of 5 mg per kg of body weight.

(If you have any information about problems caused by long term low dosing I'd be really interested to read it).


We need to drown more mice to be sure.


It would be interesting to see how the various research chemicals out there - deschloroketamine, ephenidine, and others - would fare. There are anecdotal reports of varying levels of the antidepressant effect and they shouldn't be left unacknowledged.


Depression, like obesity, is acquired, habitual change due to environmental factors. Non fraudulent CBT (active traveling in a unfamilar environment as a simplest example) is enough to introduce persistent changes (that is why there are so many stories about profound changes people undergo after visiting the East - radical behavioral change will lead, through conditioning, to change in biochemistry - body is a dynamic, adaptive system).

There is, of course, no way to change one's physical or mental conditions without introducing changes to habits, daily routines and environment.


This is, of course, bullshit. I know two friends who acquired their depression genetically from their parents, and it manifested itself in them, and their siblings as well. At times they were extremely suicidal, and they described it as waking up and wanting to kill themselves every day, and not killing themselves was the biggest struggle they ever faced.


Genetic depression is really bullshit.) These "genes" would have been wiped out in a few generations.

Genetics does not work that way.) Behavior straight out of genes, without social and environmental conditioning is bullshit. Behavior is product of training and acquired habits, guided by hard-wired instincts and emotions.

There might be some predispositions - mutations which introduce minor changes (there cannot be major ones - changes must be small and gradual enough for the organizm to cope with) into some locations, which affect sensitivity to certain chemical compound (hormones, neurotransmitters) or minor structural changes which affects metabolism, but all this could be easily compensated by behavioral patterns on a higher level.

Animals and people with sudden traumas leading to disability are doing this, but way too sophisticated, self-obsessed hipstes and couch potatoes cannot.


Right, just like all other diseases. If any disease had a genetic origin, it would be wiped out within a few generations.

Oh, except for all of these: https://en.wikipedia.org/wiki/List_of_genetic_disorders

There are even lots of diseases that provide strange benefits that protect the sufferer from other illnesses. Having half the genes for sickle-cell trait will give you strong resistance to malaria. Having both is a terrible illness. Huntington's Disease seems to provide resistance to certain types of cancers, but when you turn 35 or 40 your life becomes a real nightmare.

The point is that the purpose of genetics is not to promote healthy humans, it's to promote the reproduction of the group of genes in question. Genes will use all kinds of tricky methods to duplicate themselves, including all kinds of things that are awful for the person with them.


What is the genetic basis of depression, according to which set of successfully replicated experiments?

What is the experimentaly supported cause of depression, what are the pathological changes, in which areas, caused by which genes?


Truthfully? I don't know. That's why I didn't state depression was genetic or provided any benefit to those who suffer from it.

My point is merely that stating depression can't be genetic because of its negative effects misunderstands genetics, evolution. I'm not saying your conclusion is incorrect- there may not be a genetic component to depression at all- but I am saying your methodology for coming to that conclusion is wrong.


> "Behavior straight out of genes ... is bullshit" > "Behavior is product of ... hard-wired instincts"

Congratulations on contradicting yourself in two sentences! Or how do you suppose hard-wired instincts are hardwired?


LOL! okay keep doing what you're doing.


‘Researchers have found that CBT is roughly half as effective in treating depression as it used to be’

http://www.theguardian.com/lifeandstyle/2015/jul/03/why-cbt-...


Why should I take a tabloid story that refers to a study which is unaware of profound cross-cultural differences in what depression is seriously?

Like obesity, it is an acquired, habitual disorder due to certain "standards of life", overconsumption and resulting pathological behavioral patterns, similar in nature to autoimmune diseases, BTW. It is due to major environmental, not genetic factors.


Then, like any culturally-mediated behavior, it changes over time. People responded to CBT before, now they respond less. Chemical interventions sometimes work. I'm confused by your stubbornness on this point.


This may very well be true, however, some people may still need help in the form of drugs to get them to a point where they can actually begin to make those changes.


sounds good. so how do i get off my ass and do it?


Like everyone else.


You sure have the answers, pal.


There was a guy named Jack Kerouac, among many.

One could literally see how it works for others.


Puzzled (but also fascinated) at your motivation to post ignorant and seemingly inflammatory comments like this. But, there's probably a CBT treatment for it, right? Please let us know how the treatment goes.


The meaning was that roughly two thirds of world's classic literature is about how people are capable to alter their life circumstances and conditioning.

There might be a legitimate question of which particular CBT is more efficient, but there is no question of whether or not it works.

Smart people usually bootstraping individual CBTs for themselves. Some, like Hermann Hesse, even wrote books about it.


One of the many mistakes you've made in your string of bad posting is the assumption that all brains behave the same. Another mistake is being histrionic as hell. Maybe you could CBT some of that away by not posting.


You mean the Jack Kerouac who ended up drinking himself to death? Perhaps the road trips did not cure all ails.


Consider the magnitude change his character had undergo after he left mom's basement in New York.

Kerouac himself was smart-enough to realize the dynamic and illusory nature of what we call "myself" (it was one of his main themes - unfolding of Cody and himself and of everything else) and that his alcoholism was the cause of his suffering.

Why he didn't choose to fight it is another question. Perhaps, it was too late.




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