23 ms·

Ketamine 'exciting' depression therapy

125 points by piokuc 13y ago

dfc 13y ago
I am not sure why they linked to sagepub but not the actual article. The full text journal article is available: http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.abstract http://jop.sagepub.com/content/early/2014/03/17/026988111452...
- davidgerard 13y ago
  It was a lot of work to get BBC to link even that much. I would suggest a polite note thanking them for the link, and suggesting how to make it even more helpful :-)
kh_hk 13y ago
Mhmm.. funny the article mentions it's an illegal party drug but not that is widely used in veterinary anesthesia.
- jrabone 13y ago
  You mean, apart from the bit at the end which says: The Home Office is reclassifying ketamine in the UK to be a class B drug, although it is already used in medicine for the treatment of back pain and as an anaesthetic.
  - jawr 13y ago
    I think it's also used on infants as well as it is does not effect the respiratory system.
- corndoge 13y ago
  Too true. Unfortunately, in the eyes of almost all world governments, any drug that's enjoyable seems to automatically lose any medically useful properties it may possess. It's a sad situation that could be fixed with real drug education and not the one-sided propaganda programs (D.A.R.E. and friends) that substitute for it.
- chimeracoder 13y ago
  And in humans, too! If you've had a colonoscopy, you may have been administered ketamine before the procedure.
cLeEOGPw 13y ago
> Some patients who have faced incurable depression for decades have had symptoms disappear within hours of taking low doses of the drug. So in other words they are getting high.
- sivetic 13y ago
  Yes, they are getting "high". I'm not sure what your point is however. I've never understood the stigma associated with all mind-altering drugs, regardless the relative 'safety' of certain drugs in comparison to legal, and far more dangerous alternatives (nicotine and alcohol).
  - lutusp 13y ago
    > I've never understood the stigma associated with all mind-altering drugs ... One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression. Remember that this treatment, like all depression treatments, is symptomatic. It doesn't either identify or treat the underlying condition, only its symptoms.
    - TillE 13y ago
      Drug-induced euphoria and depression are not mutually exclusive feelings. Ask any depressed person who's taken psychoactive drugs. If ketamine functions as an antidepressant, that's a distinct and unusual effect.
      - abruzzi 13y ago
        Very true. Some hallucinogenic can significantly intensify depression.
    - dragonwriter 13y ago
      > One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression. That's an insane objection, because understanding of how different depressions (depression isn't one thing, its just a set of symptoms) respond to different treatments is one method of determining the causes. Linking observed symptoms to environmental factors (both those that precede the symptoms, those that occur with the symptoms, and those that cause changes to the symptoms) is a fairly essential part of the normal scientific method of determining the mechanism behind the symptoms. That it also helps people in the here and now is a not insignificant side benefit, of course.
JPKab 13y ago
While I was in university, I suffered (not knowingly at the time) from pretty bad depression. I basically was extremely self-destructive, and at 19 was experimenting with various drugs. My roommate's girlfriend stole a half used bottle of ketamine from a veterinary clinic she worked at. They dried the liquid into powder form in the microwave, and we all used it by snorting it. (as I said, I was hell bent on self destruction) Obviously, whatever dose we obtained would be far, far beyond a clinical amount. I immediately sank into what is called a "k-hole" and had what is often described as an "out of body" sensation. I was 5 years old again, walking along the beach in winter, looking through my father's binoculars at the humpback whales. A feeling of peace and calm came to me, and some amount of time later (perhaps an hour) I awoke from the "k-hole." The sense of peace I felt remained. I wasn't intoxicated, nor did I feel any other effects. I just felt like I had before my girlfriend had died two years before. That was the last time I touched a drug other than alcohol or marijuana.
- chimeracoder 13y ago
  I have heard similar experiences for MDMA treating PTSD. (There are also a number of studies suggesting its effectiveness when used in conjunction with talk therapy to treat PTSD). If you're interested in learning more, MAPS[0] has a ton of info. [0] http://www.maps.org/ http://www.maps.org/
- Blahah 13y ago
  To my knowledge I never suffered from depression. When I was a teenager I also experimented with various drugs. At age around 17 me and some friends took a lot of ketamine at a friend's house one night. We went out for a walk at at some point I started k-holing. We were walking along a train line at the time. I collapsed on the line and watched myself lying there. My friends hadn't noticed me fall, they'd carried on. Then I calmly watched myself get hit by a train. I watched my bloody corpse lying there for quite a while. I came back to my senses lying by the rails in a puddle of my own vomit. I hadn't really been hit by the train, although I had watched it, seen my body crumble and split. I spent the next several hours vomiting and feeling atrocious. Ever since then, I occasionally see the image of my own dead body again. That was the last time I touched ketamine, though I carried on experimenting with everything else until my early 20s. Not to detract from your experience, but ketamine can be a disgusting, dangerous drug, and taking it at home is not a sensible approach to depression, drug addiction, or anything.
veganarchocap 13y ago
Well, on a drug where you've forgotten the difference between up and down and are now convinced you're able to walk through solid objects, I'm pretty sure you'd forget about being depressed...
- Zigurd 13y ago
  This is your brain on ONDCP propaganda.
  - bbrian 13y ago
    Yeah, that seems a bit uninformed, though lots of people I know who like other drugs don't like ketamine. Cocaine, ecstasy and cannabis, when you're used to it, modify rather than replace what you're feeling. Ketamine can put you on the floor quite easily, with no/a crazy understanding of the world followed by twenty minutes of learning to understand it again. A lot of people don't like that. It can be taken in more moderate doses too, but it's hard to judge how much to take (how long is a line -- the same as a piece of string; tolerance develops quickly) and one can inadvertently take too much. I think it's under-appreciated and find the experience exhilarating.
- natdempk 13y ago
  I think the key takeaway here was that the anti-depressive effects lasted for days to months afterwards, well past the peak effects/activity of the drug.
- jsn 13y ago
  I don't know why you are being downvoted. My understanding is that yes, that's more or less how it works. Speaking from experience, whatever it is you are obsessing about, a ketamine trip makes you forget about it for about an hour. I think the main feeling you get when coming down from the trip is that you were just shown a world where your obsession doesn't make any sense, and it's a very good time to question your obsessions.
  - veganarchocap 13y ago
te_platt 13y ago
Very interesting. There have also been recent studies on the effects of anesthesia (Isoflurane in particular) on depression. See: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069809 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna... I thought the ketamine therapy was especially interesting in that it had good effect with relatively low doses. In the Isoflurane study they would put patients completely under (asleep? What is the technical term for being unconscious under anesthesia?) for about 15 minutes. Makes me wonder about the relation between sleep problems and depression.
- noir_lord 13y ago
  > Makes me wonder about the relation between sleep problems and depression. There is fairly strong evidence that sleep deprivation can trigger or exasperate depression [1]. As someone who has had chronic cyclical insomnia since my teens (17 years) in my case it has a massive effect. When I'm coming out of an insomnia phase the first couple of days where I get a proper nights sleep I feel like I'm on drugs, it's a feeling of well-being and euphoria that is hard to describe, I have limitless energy and I'm enthusiastic about all the things I love to do. When I'm in the middle of the no-sleep cycle, I struggle to do even basic tasks and anything requiring complete focus is basically ruled out, the world is a grey dreary place, summoning the energy to do anything is a major challenge. I manage my insomnia without drugs (the problem with sleeping pills in my experience is that while they do make you sleep it's not a high quality sleep and that combined with the lag from the pills means I don't feel any better with them than without) by impeccable sleep hygiene, diet and exercise and the knowledge that eventually the cycle will end. [1] http://www.ncbi.nlm.nih.gov/books/NBK19961/ http://www.ncbi.nlm.nih.gov/books/NBK19961/
  - lutusp 13y ago
    > There is fairly strong evidence that sleep deprivation can trigger or exasperate [sic] depression ... This is one I'm seeing more and more often. The word you were after is "exacerbate". It's my hope that exasperate and exacerbate won't suffer the same fate as literally and figuratively, which now mean the same thing: http://www.merriam-webster.com/dictionary/literally http://www.merriam-webster.com/dictionary/literally
fun2have 13y ago
The test was only done on 28 people and only 8 showed some improvements. The Improvements where self reported. What I wonder is the statistical error on such a small study. From this small study they are generalising to say that it is "exciting" and "dramatic"!
- natdempk 13y ago
  Usually a small study like this is done as a test of safety and potential benefit as a precursor to a larger more comprehensive study. I think its exciting and dramatic that there were enough initial positive results to move on to a better study.
  - deleted 13y ago
    [deleted]
    - gwern 13y ago
      > Other placebo-controlled studies have shown that ketamine has no effect in treating MDD (see http://journals.psychiatryonline.org/article.aspx?articleid=.. http://journals.psychiatryonline.org/article.aspx?articleid=.... for example), so this is really just a waste of time. Since when does ketamine==memantine?
- cpncrunch 13y ago
  Also interesting is the fact that the results are in the range that would be expected by the placebo effect.
  - deleted 13y ago
    [deleted]
jasonkolb 13y ago
"It shows that depression is something chemical, that it can be reversed with chemicals, it dispenses for once and for all that you can just pull your socks up." This is entirely an assumption, and shows nothing conclusively. Just as an experience can trigger a depression (see @JPKab) an experience can cause it to end. There's no reason to look at a human being as a walking slab of meat for the sake of analysis. This says nothing about "chemicals", and I'll bet you can find many of the same benefits are attained by people who are able to achieve similar experiences using meditation or other techniques.
- Jtsummers 13y ago
  Per the linked article, the particular test subjects had longterm depression and had undergone numerous, unsuccessful, treatments in the past. And, while that quote seems a bit too absolute in stating that "depression is something chemical". They probably should have said something like: depression can be caused by something chemical. And you are correct that for many, maybe even most, people it's probably not chemical in origin, that doesn't mean that it's never chemical.
lutusp 13y ago
Two quotes from the article: 1. "Eight showed improvements in reported levels of depression, with four of them improving so much they were no longer classed as depressed. Some responded within six hours of the first infusion of ketamine." 2. "Lead researcher Dr Rupert McShane said: 'It really is dramatic for some people, it's the sort of thing really that makes it worth doing psychiatry, it's a really wonderful thing to see.'" [emphasis added] Wait ... what? Saying, "Take this pill and you'll feel better" isn't how psychiatry is (or was) defined. That isn't psychiatry, it's pharmacology. Also, none of the treatments, the old ones like talk therapy, or the new ones including drugs and/or deep-brain stimulation, suggest or identify a cause for depression. So far we've only been treating the symptoms of a disease whose cause we don't know. I long for the good old days, the days of science, when we identified the cause of a disease, then designed a cure based on our understanding of its cause. This isn't a cure, it's a symptomatic treatment, and to remain effective it would have to continue forever, reliant on a drug whose mechanism is as unknown as the thing being treated, just as with ADHD and PTSD. I'm sure Big Pharma is very upset that another perpetual market for drugs is opening up.
- jonahx 13y ago
  The "good old days" of psychiatry were a far cry from "the days of science."
  - lutusp 13y ago
    Yes -- as true now as it was then. But moving away from talk therapy toward symptomatic drug treatment moves neither toward nor away from science. Also, by "the good old days" I was referring to the medical practice of first identifying a disease's cause, then designing a cure. Most mental illnesses don't have this property, which open them up to exploitation by Big Pharma.
    - jonahx 13y ago
      Agree that things haven't progressed much toward an ideal of rigorous science, but the process you're lauding of first identifying a cause and then designing a cure doesn't mean much when you're just making up stories for both things, which is essentially what those good old days were.
throwaway8484 13y ago
Several years ago and for a period of around 5 months I took Ketamine recreationally. I was taking it nearly everyday and besides the effect of the drug itself, the resulting lifting of depression was very strong. It got to a point where I had feelings of intense love for people and my interactions became very emotionally charged in a positive way. I also noticed that I had higher levels of clarity and my writing and thinking became clearer. The only explanation I've found is that ketamine reduces the level of kynurenic acid in the brain, something that I've found to have higher levels of. As I started taking it less depression would start to kick back in 5-7 days. A relatively small dosage (not enough to get back in to a k-hole) would get rid of the depression almost instantly. But there was a critical downside. After a while I noticed that my ability to do technical work diminished greatly. It made me stupider in many ways. I felt like I did not have access to the portion of my brain in which I could code. On the flipside it seemed to make me smarter socially, or at least give the impression as the increased verbal clarity and feelings of connection to people. From looking around at other users at the time, I would say the effects of increased clarity were not commonly reported, and the anti-depression effect wasn't really talked about much, yet people got quite addicted to it. At the end of around 5 months, I stopped taking it completely. I couldn't do it and hold down a technical job.
- RankingMember 13y ago
  I'm curious: what kind of test did you undergo that let you see how much kynurenic acid you have in your brain?
tokenadult 13y ago
Treatment of depression has improved enormously over the last four decades. It's a tough treatment and research problem because depression isn't just one disease at the biological level. Quoting the full study abstract will probably be helpful to the discussion here. "Background: Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Method: Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4–7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Results: Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25–168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. Conclusion: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop." The free full text of the article reporting this preliminary finding can be found online.[1] (Hat tip to the participant here who first found the abstract link, which leads to the full-text link.) Depression is maddeningly difficult to treat because it is quite clear on multiple grounds that not everyone with signs of depression (extremely persistent low mood contrary to the patient's life circumstances) has the same underlying physical or psychological cause of depression. The human mood regulatory system is a SYSTEM, and as such it can be perturbed by a number of biochemical stressors internal to the patient, and also by a number of outside-the-patient environmental stressors (including sleep disturbance, already mentioned in this thread, and the use or abuse of various druggs). Not all patients have the same biological substrate to their depression, so not all patients will respond to the same treatment. To date, the most effective treatment for depression is a both-and of prescribed medication and professionally supervised talk therapy, and there is an active research program on identifying which patients respond to which medicines and to which kinds of talk therapy.[2] In any research program on treatment of human subjects, the studies have to start with small numbers of subjects to verify safety of the treatment, and then gradually increase the number of subjects and add in double-blind protocols to verify both safety and effectiveness. (The study reported here is "open label," not double-blind.) New treatments are usually tested first on patients who don't respond to current treatments, as in the research reported here. It will be a long time before we know how helpful ketamine is compared to other treatments for depression, but that will be an ongoing program of research, and so far it looks somewhat promising. [1] http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.full.pdf+html http://jop.sagepub.com/content/early/2014/03/17/026988111452... [2] http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.121208.131653?prevSearch=depression&searchHistoryKey= http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.1...
netcan 13y ago
Lately, I seem to be hearing a lot about drugs of the "psychedelic" variety being used to treat thugs like depression. psilocybin, DMT, MDMA, Ketamine. The thing that jumps out at me is that they sound like / claim to be treatments in the way that antibiotics are rather than in the way painkillers are. IE, you go through treatment and get "cured." Please correct me if I am wrong but as I understand it most medical treatments for mental illness is of the painkiller variety. It relieves symptoms while taken consistently and patients either stay medicated indefinitely or the illness runs its course while the effects are mitigated by the drug. Are there any established treatments that we understand well of the antibiotics variety? Mental illnesses that are cured by a course of treatment rather than and indefinitely ongoing one.
- nemo1618 13y ago
  Psychedelics are certainly not drugs in the antibiotic sense; they don't seek out depression-causing neurons and cure them or anything remotely like that. Rather, psychedelic drugs offer a means for the user to "get out of their head" for a bit. In the right set and setting, the experience offers an opportunity for intense introspection. “Psychedelics probably work in addiction by making the brain function more chaotically for a period — a bit like shaking up a snow globe — weakening reinforced brain connections and dynamics.” It is the experience, not the drug, which causes a fundamental shift in attitude/mindset/worldview, and that is what "cures" the illness.
justinpaulson 13y ago
This is very interesting for the use of ketamine. My wife is currently undergoing a ketamine infusion for RSD/CRPS. RSD/CRPS is a crippling pain disorder, and ketamine infusions are so far the only thing that has given her any relief. Hopefully things like this will help to get ketamine treatments covered by insurance, because it is insane that they are not covered for those suffering RSD/CRPS.
tibbon 13y ago
I've had friends experiment with this, and they've reported good effects from taking small doses to help with depression. In small amounts, it isn't as scary of a drug as most people make it sound like. In small doses, its kinda like being tipsy (acts on similar receptors to alcohol), and if you know what you're doing there isn't much of a chance of 'accidentally' going into a K-hole, as its roughly a magnitude of difference between what you need to take for basic effects and a K-hole.
llamataboot 13y ago
Many people at bluelight.ru have blogged extensively about their experiences using ketamine to treat bipolar depression and major depression. The general consensus seems to be that using doses low enough to not feel any effect with very frequent dosing (every hour or so over the course of a few days) seems to have the strongest effects. I have tried both this route and the more traditional k-hole route to self-treat treatment resistant depression but haven't noticed much of an effect with either route in the long term. In the short term, I rather enjoy the psychedelic experience of ketamine trips. It is a rather "more-ish" drug though, because it is both short-lasting and hits dopamine so I urge people to experiment responsibility (ie; lay out the ketamine you are going to do, put the rest away, and don't touch it no matter how much you think one more line will be useful/fun)
funkjunky 13y ago
I was a ketamine user for over a decade. It really did work wonders for clinical depression, even brought me right out of suicidal hysteria and despair within moments, but it comes with severe drawbacks. It can ruin your bladder. It will sap the b vitamins out of your system, and could cause nerve damage. More importantly, it is VERY addictive psychologically. I'm not saying to stay away, but to be careful and disciplined. Thoughts on the research: to the extent that the mind is already chemical in nature, yes depression can be a chemical issue. However, I think they are looking at it all wrong. I believe the reason ketamine (and nitrous oxide, they may soon find out) are so effective at attacking depression is because they are disassociative in nature. Looking at it as simply a chemical problem erroneously reduces what is likely a complex issue in a complex organ. What ketamine and other disassociatives do is they "loosen" one's attachment and identification with various parts of their cognitive minds, allowing thoughts and feelings to exist in their own space without having such a strong hold on a person's conscious self, or seat of awareness, or whatever. Its basically like induced meditation, and from my experience with both disassociatives and years of meditation, I will tell you that they are VERY similar and the ancient traditions of buddhism and yoga got the nature of the mind and depression more right than any of the shit I learned in university or this kind of research. Meditation WORKS, it just takes practice and discipline. Like brushing teeth, but for the mind. If you dont do it, you will get plaque and your mind will rot. A drug may help pull a person out of the depression temporarily, which is definitely useful in times when a person can't break out of the loop and is immobilized with despair, but to reduce the whole thing down to this chemical or that chemical will only continue to find chemical solutions, which are never ideal.
- sizzle 13y ago
  very insightful post, thanks for sharing your thoughts. I think I'll give meditation a go
  - funkjunky 13y ago
    The best piece of advice I can give you is to do whatever you can to make, and keep, it as a daily habit. It is far better to do 5-10 minutes every morning than half an hour once a week. If you want any good resources, I've got a great list of books to choose from, but whatever method you just make sure you stick to it regularly. Think of it like brushing your teeth, brushing 3 times as long every 3 days doesn't work as well as brushing a shorter amount of time every day.
orf 13y ago
I remember reading about this in a New scientist issue over 8 years ago. It's a shame that it's taken this long for newsworthy studies to be done on it.
Reallynow 13y ago
A few points: This is not just getting high. The antidepressant effects far outlast the brief trippy effects, which is an important reason why science is interested. Although this is a small sample, this is not the first study of this antidepressant effect, which had been studied since at least 2000 (citation at end). I'd guess this study is probably getting extra attention from the BBC because of it's from a British group of researchers. This area of research is important both because it's a new mechanism of antidepressant (opening doors to other drugs and a better understanding of depression) and it is faster acting than other antidepressants, which improve mood slowly over weeks. For the suicidal, this wait can be a lifetime. There's currently a super interesting (to some of us) question about how important the acute trippy effects are to the sustained antidepressant effects. Is this something where we can engineer out the psychedelic components or are these somehow part of the antidepressant mechanism? See for example this paywalled paper from Zatare's group, which correlates what they call 'dissociative' effects with the antidepressant effect http://www.sciencedirect.com/science/article/pii/S016503271400055X http://www.sciencedirect.com/science/article/pii/S0165032714... (An early paper on the phenomenon is Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–354. Paywalled http://www.biologicalpsychiatryjournal.com/article/S0006-3223(99)00230-9/abstract http://www.biologicalpsychiatryjournal.com/article/S0006-322... )
0800899g 13y ago
ketamine
davidgerard 13y ago
THE WHITE ROOM, Trancentral, Thursday (NTNME) — The illegal party drug ketamine is an “exciting” and “dramatic” new treatment for depression, say doctors who waited about two decades too long before conducting the first trials in the UK. The single small study has attracted due caution from evidence-based medicine experts, since 80% of single studies turn out to be in error. However, middle-aged doctors and researchers who feel they didn’t get out enough in their youth are clamouring to do multiple large-scale replications of the study, probably this weekend. The findings open up whole new avenues of research. “It’s the sort of thing really that makes it worth doing psychiatry,” said lead researcher Dr Rupert McShane, or, as he now calls himself, DJ Rupe McK-Hole. “Can we get back into trials on LSD yet? I understand there’s also considerable clinical possibilities for the therapeutic qualities of sequences of repetitive beats, MDMA and the possibility of shagging cute raver chicks like the ones I remember.” The duration of the effect is still a problem. “We’ll have to make sure we repeat the trials next weekend and the weekend after as well. For science and verifiability.”
zxexz 13y ago
I wonder what the effects of other arylcyclohexylamine compounds have on depression. There is plenty of anecdotal evidence on Bluelight.ru and Erowid.org suggesting that other chemicals of this class can have a positive impact on depression. Of course, there are plenty reports of addiction and negative behavior (mostly with PCP). I know that many people report the legal analogue Methoxetamine (legal in the US; Ketamine is schedule III and the federal analogue act only applies to schedules I and II) has potent antidepressant effects.

125 points by piokuc 13y ago

dfc 13y ago

I am not sure why they linked to sagepub but not the actual article. The full text journal article is available: http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.abstract http://jop.sagepub.com/content/early/2014/03/17/026988111452...

davidgerard 13y ago
It was a lot of work to get BBC to link even that much. I would suggest a polite note thanking them for the link, and suggesting how to make it even more helpful :-)

kh_hk 13y ago

Mhmm.. funny the article mentions it's an illegal party drug but not that is widely used in veterinary anesthesia.

jrabone 13y ago
You mean, apart from the bit at the end which says: The Home Office is reclassifying ketamine in the UK to be a class B drug, although it is already used in medicine for the treatment of back pain and as an anaesthetic.
- jawr 13y ago
  I think it's also used on infants as well as it is does not effect the respiratory system.
corndoge 13y ago
Too true. Unfortunately, in the eyes of almost all world governments, any drug that's enjoyable seems to automatically lose any medically useful properties it may possess. It's a sad situation that could be fixed with real drug education and not the one-sided propaganda programs (D.A.R.E. and friends) that substitute for it.
chimeracoder 13y ago
And in humans, too! If you've had a colonoscopy, you may have been administered ketamine before the procedure.

cLeEOGPw 13y ago

> Some patients who have faced incurable depression for decades have had symptoms disappear within hours of taking low doses of the drug. So in other words they are getting high.

sivetic 13y ago
Yes, they are getting "high". I'm not sure what your point is however. I've never understood the stigma associated with all mind-altering drugs, regardless the relative 'safety' of certain drugs in comparison to legal, and far more dangerous alternatives (nicotine and alcohol).
- lutusp 13y ago
  > I've never understood the stigma associated with all mind-altering drugs ... One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression. Remember that this treatment, like all depression treatments, is symptomatic. It doesn't either identify or treat the underlying condition, only its symptoms.
  - TillE 13y ago
    Drug-induced euphoria and depression are not mutually exclusive feelings. Ask any depressed person who's taken psychoactive drugs. If ketamine functions as an antidepressant, that's a distinct and unusual effect.
    - abruzzi 13y ago
      Very true. Some hallucinogenic can significantly intensify depression.
  - dragonwriter 13y ago
    > One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression. That's an insane objection, because understanding of how different depressions (depression isn't one thing, its just a set of symptoms) respond to different treatments is one method of determining the causes. Linking observed symptoms to environmental factors (both those that precede the symptoms, those that occur with the symptoms, and those that cause changes to the symptoms) is a fairly essential part of the normal scientific method of determining the mechanism behind the symptoms. That it also helps people in the here and now is a not insignificant side benefit, of course.

JPKab 13y ago

While I was in university, I suffered (not knowingly at the time) from pretty bad depression. I basically was extremely self-destructive, and at 19 was experimenting with various drugs. My roommate's girlfriend stole a half used bottle of ketamine from a veterinary clinic she worked at. They dried the liquid into powder form in the microwave, and we all used it by snorting it. (as I said, I was hell bent on self destruction) Obviously, whatever dose we obtained would be far, far beyond a clinical amount. I immediately sank into what is called a "k-hole" and had what is often described as an "out of body" sensation. I was 5 years old again, walking along the beach in winter, looking through my father's binoculars at the humpback whales. A feeling of peace and calm came to me, and some amount of time later (perhaps an hour) I awoke from the "k-hole." The sense of peace I felt remained. I wasn't intoxicated, nor did I feel any other effects. I just felt like I had before my girlfriend had died two years before. That was the last time I touched a drug other than alcohol or marijuana.

chimeracoder 13y ago
I have heard similar experiences for MDMA treating PTSD. (There are also a number of studies suggesting its effectiveness when used in conjunction with talk therapy to treat PTSD). If you're interested in learning more, MAPS[0] has a ton of info. [0] http://www.maps.org/ http://www.maps.org/
Blahah 13y ago
To my knowledge I never suffered from depression. When I was a teenager I also experimented with various drugs. At age around 17 me and some friends took a lot of ketamine at a friend's house one night. We went out for a walk at at some point I started k-holing. We were walking along a train line at the time. I collapsed on the line and watched myself lying there. My friends hadn't noticed me fall, they'd carried on. Then I calmly watched myself get hit by a train. I watched my bloody corpse lying there for quite a while. I came back to my senses lying by the rails in a puddle of my own vomit. I hadn't really been hit by the train, although I had watched it, seen my body crumble and split. I spent the next several hours vomiting and feeling atrocious. Ever since then, I occasionally see the image of my own dead body again. That was the last time I touched ketamine, though I carried on experimenting with everything else until my early 20s. Not to detract from your experience, but ketamine can be a disgusting, dangerous drug, and taking it at home is not a sensible approach to depression, drug addiction, or anything.

veganarchocap 13y ago

Well, on a drug where you've forgotten the difference between up and down and are now convinced you're able to walk through solid objects, I'm pretty sure you'd forget about being depressed...

Zigurd 13y ago
This is your brain on ONDCP propaganda.
- bbrian 13y ago
  Yeah, that seems a bit uninformed, though lots of people I know who like other drugs don't like ketamine. Cocaine, ecstasy and cannabis, when you're used to it, modify rather than replace what you're feeling. Ketamine can put you on the floor quite easily, with no/a crazy understanding of the world followed by twenty minutes of learning to understand it again. A lot of people don't like that. It can be taken in more moderate doses too, but it's hard to judge how much to take (how long is a line -- the same as a piece of string; tolerance develops quickly) and one can inadvertently take too much. I think it's under-appreciated and find the experience exhilarating.
natdempk 13y ago
I think the key takeaway here was that the anti-depressive effects lasted for days to months afterwards, well past the peak effects/activity of the drug.
jsn 13y ago
I don't know why you are being downvoted. My understanding is that yes, that's more or less how it works. Speaking from experience, whatever it is you are obsessing about, a ketamine trip makes you forget about it for about an hour. I think the main feeling you get when coming down from the trip is that you were just shown a world where your obsession doesn't make any sense, and it's a very good time to question your obsessions.
- veganarchocap 13y ago

te_platt 13y ago

Very interesting. There have also been recent studies on the effects of anesthesia (Isoflurane in particular) on depression. See: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069809 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna... I thought the ketamine therapy was especially interesting in that it had good effect with relatively low doses. In the Isoflurane study they would put patients completely under (asleep? What is the technical term for being unconscious under anesthesia?) for about 15 minutes. Makes me wonder about the relation between sleep problems and depression.

noir_lord 13y ago
> Makes me wonder about the relation between sleep problems and depression. There is fairly strong evidence that sleep deprivation can trigger or exasperate depression [1]. As someone who has had chronic cyclical insomnia since my teens (17 years) in my case it has a massive effect. When I'm coming out of an insomnia phase the first couple of days where I get a proper nights sleep I feel like I'm on drugs, it's a feeling of well-being and euphoria that is hard to describe, I have limitless energy and I'm enthusiastic about all the things I love to do. When I'm in the middle of the no-sleep cycle, I struggle to do even basic tasks and anything requiring complete focus is basically ruled out, the world is a grey dreary place, summoning the energy to do anything is a major challenge. I manage my insomnia without drugs (the problem with sleeping pills in my experience is that while they do make you sleep it's not a high quality sleep and that combined with the lag from the pills means I don't feel any better with them than without) by impeccable sleep hygiene, diet and exercise and the knowledge that eventually the cycle will end. [1] http://www.ncbi.nlm.nih.gov/books/NBK19961/ http://www.ncbi.nlm.nih.gov/books/NBK19961/
- lutusp 13y ago
  > There is fairly strong evidence that sleep deprivation can trigger or exasperate [sic] depression ... This is one I'm seeing more and more often. The word you were after is "exacerbate". It's my hope that exasperate and exacerbate won't suffer the same fate as literally and figuratively, which now mean the same thing: http://www.merriam-webster.com/dictionary/literally http://www.merriam-webster.com/dictionary/literally

fun2have 13y ago

The test was only done on 28 people and only 8 showed some improvements. The Improvements where self reported. What I wonder is the statistical error on such a small study. From this small study they are generalising to say that it is "exciting" and "dramatic"!

natdempk 13y ago
Usually a small study like this is done as a test of safety and potential benefit as a precursor to a larger more comprehensive study. I think its exciting and dramatic that there were enough initial positive results to move on to a better study.
- deleted 13y ago
  [deleted]
  - gwern 13y ago
    > Other placebo-controlled studies have shown that ketamine has no effect in treating MDD (see http://journals.psychiatryonline.org/article.aspx?articleid=.. http://journals.psychiatryonline.org/article.aspx?articleid=.... for example), so this is really just a waste of time. Since when does ketamine==memantine?
cpncrunch 13y ago
Also interesting is the fact that the results are in the range that would be expected by the placebo effect.
- deleted 13y ago
  [deleted]

jasonkolb 13y ago

"It shows that depression is something chemical, that it can be reversed with chemicals, it dispenses for once and for all that you can just pull your socks up." This is entirely an assumption, and shows nothing conclusively. Just as an experience can trigger a depression (see @JPKab) an experience can cause it to end. There's no reason to look at a human being as a walking slab of meat for the sake of analysis. This says nothing about "chemicals", and I'll bet you can find many of the same benefits are attained by people who are able to achieve similar experiences using meditation or other techniques.

Jtsummers 13y ago
Per the linked article, the particular test subjects had longterm depression and had undergone numerous, unsuccessful, treatments in the past. And, while that quote seems a bit too absolute in stating that "depression is something chemical". They probably should have said something like: depression can be caused by something chemical. And you are correct that for many, maybe even most, people it's probably not chemical in origin, that doesn't mean that it's never chemical.

lutusp 13y ago

Two quotes from the article: 1. "Eight showed improvements in reported levels of depression, with four of them improving so much they were no longer classed as depressed. Some responded within six hours of the first infusion of ketamine." 2. "Lead researcher Dr Rupert McShane said: 'It really is dramatic for some people, it's the sort of thing really that makes it worth doing psychiatry, it's a really wonderful thing to see.'" [emphasis added] Wait ... what? Saying, "Take this pill and you'll feel better" isn't how psychiatry is (or was) defined. That isn't psychiatry, it's pharmacology. Also, none of the treatments, the old ones like talk therapy, or the new ones including drugs and/or deep-brain stimulation, suggest or identify a cause for depression. So far we've only been treating the symptoms of a disease whose cause we don't know. I long for the good old days, the days of science, when we identified the cause of a disease, then designed a cure based on our understanding of its cause. This isn't a cure, it's a symptomatic treatment, and to remain effective it would have to continue forever, reliant on a drug whose mechanism is as unknown as the thing being treated, just as with ADHD and PTSD. I'm sure Big Pharma is very upset that another perpetual market for drugs is opening up.

jonahx 13y ago
The "good old days" of psychiatry were a far cry from "the days of science."
- lutusp 13y ago
  Yes -- as true now as it was then. But moving away from talk therapy toward symptomatic drug treatment moves neither toward nor away from science. Also, by "the good old days" I was referring to the medical practice of first identifying a disease's cause, then designing a cure. Most mental illnesses don't have this property, which open them up to exploitation by Big Pharma.
  - jonahx 13y ago
    Agree that things haven't progressed much toward an ideal of rigorous science, but the process you're lauding of first identifying a cause and then designing a cure doesn't mean much when you're just making up stories for both things, which is essentially what those good old days were.

throwaway8484 13y ago

Several years ago and for a period of around 5 months I took Ketamine recreationally. I was taking it nearly everyday and besides the effect of the drug itself, the resulting lifting of depression was very strong. It got to a point where I had feelings of intense love for people and my interactions became very emotionally charged in a positive way. I also noticed that I had higher levels of clarity and my writing and thinking became clearer. The only explanation I've found is that ketamine reduces the level of kynurenic acid in the brain, something that I've found to have higher levels of. As I started taking it less depression would start to kick back in 5-7 days. A relatively small dosage (not enough to get back in to a k-hole) would get rid of the depression almost instantly. But there was a critical downside. After a while I noticed that my ability to do technical work diminished greatly. It made me stupider in many ways. I felt like I did not have access to the portion of my brain in which I could code. On the flipside it seemed to make me smarter socially, or at least give the impression as the increased verbal clarity and feelings of connection to people. From looking around at other users at the time, I would say the effects of increased clarity were not commonly reported, and the anti-depression effect wasn't really talked about much, yet people got quite addicted to it. At the end of around 5 months, I stopped taking it completely. I couldn't do it and hold down a technical job.

RankingMember 13y ago
I'm curious: what kind of test did you undergo that let you see how much kynurenic acid you have in your brain?

tokenadult 13y ago

Treatment of depression has improved enormously over the last four decades. It's a tough treatment and research problem because depression isn't just one disease at the biological level. Quoting the full study abstract will probably be helpful to the discussion here. "Background: Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Method: Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4–7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Results: Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25–168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. Conclusion: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop." The free full text of the article reporting this preliminary finding can be found online.[1] (Hat tip to the participant here who first found the abstract link, which leads to the full-text link.) Depression is maddeningly difficult to treat because it is quite clear on multiple grounds that not everyone with signs of depression (extremely persistent low mood contrary to the patient's life circumstances) has the same underlying physical or psychological cause of depression. The human mood regulatory system is a SYSTEM, and as such it can be perturbed by a number of biochemical stressors internal to the patient, and also by a number of outside-the-patient environmental stressors (including sleep disturbance, already mentioned in this thread, and the use or abuse of various druggs). Not all patients have the same biological substrate to their depression, so not all patients will respond to the same treatment. To date, the most effective treatment for depression is a both-and of prescribed medication and professionally supervised talk therapy, and there is an active research program on identifying which patients respond to which medicines and to which kinds of talk therapy.[2] In any research program on treatment of human subjects, the studies have to start with small numbers of subjects to verify safety of the treatment, and then gradually increase the number of subjects and add in double-blind protocols to verify both safety and effectiveness. (The study reported here is "open label," not double-blind.) New treatments are usually tested first on patients who don't respond to current treatments, as in the research reported here. It will be a long time before we know how helpful ketamine is compared to other treatments for depression, but that will be an ongoing program of research, and so far it looks somewhat promising. [1] http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.full.pdf+html http://jop.sagepub.com/content/early/2014/03/17/026988111452... [2] http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.121208.131653?prevSearch=depression&searchHistoryKey= http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.1...

netcan 13y ago

Lately, I seem to be hearing a lot about drugs of the "psychedelic" variety being used to treat thugs like depression. psilocybin, DMT, MDMA, Ketamine. The thing that jumps out at me is that they sound like / claim to be treatments in the way that antibiotics are rather than in the way painkillers are. IE, you go through treatment and get "cured." Please correct me if I am wrong but as I understand it most medical treatments for mental illness is of the painkiller variety. It relieves symptoms while taken consistently and patients either stay medicated indefinitely or the illness runs its course while the effects are mitigated by the drug. Are there any established treatments that we understand well of the antibiotics variety? Mental illnesses that are cured by a course of treatment rather than and indefinitely ongoing one.

nemo1618 13y ago
Psychedelics are certainly not drugs in the antibiotic sense; they don't seek out depression-causing neurons and cure them or anything remotely like that. Rather, psychedelic drugs offer a means for the user to "get out of their head" for a bit. In the right set and setting, the experience offers an opportunity for intense introspection. “Psychedelics probably work in addiction by making the brain function more chaotically for a period — a bit like shaking up a snow globe — weakening reinforced brain connections and dynamics.” It is the experience, not the drug, which causes a fundamental shift in attitude/mindset/worldview, and that is what "cures" the illness.

justinpaulson 13y ago

This is very interesting for the use of ketamine. My wife is currently undergoing a ketamine infusion for RSD/CRPS. RSD/CRPS is a crippling pain disorder, and ketamine infusions are so far the only thing that has given her any relief. Hopefully things like this will help to get ketamine treatments covered by insurance, because it is insane that they are not covered for those suffering RSD/CRPS.

tibbon 13y ago

I've had friends experiment with this, and they've reported good effects from taking small doses to help with depression. In small amounts, it isn't as scary of a drug as most people make it sound like. In small doses, its kinda like being tipsy (acts on similar receptors to alcohol), and if you know what you're doing there isn't much of a chance of 'accidentally' going into a K-hole, as its roughly a magnitude of difference between what you need to take for basic effects and a K-hole.

llamataboot 13y ago

Many people at bluelight.ru have blogged extensively about their experiences using ketamine to treat bipolar depression and major depression. The general consensus seems to be that using doses low enough to not feel any effect with very frequent dosing (every hour or so over the course of a few days) seems to have the strongest effects. I have tried both this route and the more traditional k-hole route to self-treat treatment resistant depression but haven't noticed much of an effect with either route in the long term. In the short term, I rather enjoy the psychedelic experience of ketamine trips. It is a rather "more-ish" drug though, because it is both short-lasting and hits dopamine so I urge people to experiment responsibility (ie; lay out the ketamine you are going to do, put the rest away, and don't touch it no matter how much you think one more line will be useful/fun)

funkjunky 13y ago

I was a ketamine user for over a decade. It really did work wonders for clinical depression, even brought me right out of suicidal hysteria and despair within moments, but it comes with severe drawbacks. It can ruin your bladder. It will sap the b vitamins out of your system, and could cause nerve damage. More importantly, it is VERY addictive psychologically. I'm not saying to stay away, but to be careful and disciplined. Thoughts on the research: to the extent that the mind is already chemical in nature, yes depression can be a chemical issue. However, I think they are looking at it all wrong. I believe the reason ketamine (and nitrous oxide, they may soon find out) are so effective at attacking depression is because they are disassociative in nature. Looking at it as simply a chemical problem erroneously reduces what is likely a complex issue in a complex organ. What ketamine and other disassociatives do is they "loosen" one's attachment and identification with various parts of their cognitive minds, allowing thoughts and feelings to exist in their own space without having such a strong hold on a person's conscious self, or seat of awareness, or whatever. Its basically like induced meditation, and from my experience with both disassociatives and years of meditation, I will tell you that they are VERY similar and the ancient traditions of buddhism and yoga got the nature of the mind and depression more right than any of the shit I learned in university or this kind of research. Meditation WORKS, it just takes practice and discipline. Like brushing teeth, but for the mind. If you dont do it, you will get plaque and your mind will rot. A drug may help pull a person out of the depression temporarily, which is definitely useful in times when a person can't break out of the loop and is immobilized with despair, but to reduce the whole thing down to this chemical or that chemical will only continue to find chemical solutions, which are never ideal.

sizzle 13y ago
very insightful post, thanks for sharing your thoughts. I think I'll give meditation a go
- funkjunky 13y ago
  The best piece of advice I can give you is to do whatever you can to make, and keep, it as a daily habit. It is far better to do 5-10 minutes every morning than half an hour once a week. If you want any good resources, I've got a great list of books to choose from, but whatever method you just make sure you stick to it regularly. Think of it like brushing your teeth, brushing 3 times as long every 3 days doesn't work as well as brushing a shorter amount of time every day.

orf 13y ago

I remember reading about this in a New scientist issue over 8 years ago. It's a shame that it's taken this long for newsworthy studies to be done on it.

Reallynow 13y ago

A few points: This is not just getting high. The antidepressant effects far outlast the brief trippy effects, which is an important reason why science is interested. Although this is a small sample, this is not the first study of this antidepressant effect, which had been studied since at least 2000 (citation at end). I'd guess this study is probably getting extra attention from the BBC because of it's from a British group of researchers. This area of research is important both because it's a new mechanism of antidepressant (opening doors to other drugs and a better understanding of depression) and it is faster acting than other antidepressants, which improve mood slowly over weeks. For the suicidal, this wait can be a lifetime. There's currently a super interesting (to some of us) question about how important the acute trippy effects are to the sustained antidepressant effects. Is this something where we can engineer out the psychedelic components or are these somehow part of the antidepressant mechanism? See for example this paywalled paper from Zatare's group, which correlates what they call 'dissociative' effects with the antidepressant effect http://www.sciencedirect.com/science/article/pii/S016503271400055X http://www.sciencedirect.com/science/article/pii/S0165032714... (An early paper on the phenomenon is Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–354. Paywalled http://www.biologicalpsychiatryjournal.com/article/S0006-3223(99)00230-9/abstract http://www.biologicalpsychiatryjournal.com/article/S0006-322... )

0800899g 13y ago

ketamine

davidgerard 13y ago

THE WHITE ROOM, Trancentral, Thursday (NTNME) — The illegal party drug ketamine is an “exciting” and “dramatic” new treatment for depression, say doctors who waited about two decades too long before conducting the first trials in the UK. The single small study has attracted due caution from evidence-based medicine experts, since 80% of single studies turn out to be in error. However, middle-aged doctors and researchers who feel they didn’t get out enough in their youth are clamouring to do multiple large-scale replications of the study, probably this weekend. The findings open up whole new avenues of research. “It’s the sort of thing really that makes it worth doing psychiatry,” said lead researcher Dr Rupert McShane, or, as he now calls himself, DJ Rupe McK-Hole. “Can we get back into trials on LSD yet? I understand there’s also considerable clinical possibilities for the therapeutic qualities of sequences of repetitive beats, MDMA and the possibility of shagging cute raver chicks like the ones I remember.” The duration of the effect is still a problem. “We’ll have to make sure we repeat the trials next weekend and the weekend after as well. For science and verifiability.”

zxexz 13y ago

I wonder what the effects of other arylcyclohexylamine compounds have on depression. There is plenty of anecdotal evidence on Bluelight.ru and Erowid.org suggesting that other chemicals of this class can have a positive impact on depression. Of course, there are plenty reports of addiction and negative behavior (mostly with PCP). I know that many people report the legal analogue Methoxetamine (legal in the US; Ketamine is schedule III and the federal analogue act only applies to schedules I and II) has potent antidepressant effects.