10 ms·

Ketamine lifts depression via a byproduct of its metabolism

125 points by MollyR 10y ago

openasocket 10y ago
OK, I've been skeptical in the past about studies suggesting drugs like ketamine and MDMA could be used to treat depression. Ketamine especially would not be a good anti-depressant pill, because it is highly addictive, not to mention you're giving a _depressant_ to a depressed person. However, this result is promising. This study has claimed to have isolated the anti-depressant effect to a particular product of ketamine metabolism, and that this compound contains none of the anesthetic and addictive properties. Obviously, this is just a single study, performed on mice, but it is a promising first step towards the potential development of a new anti-depressant.
- maxerickson 10y ago
  Why are you reasoning from the words used to describe it? "depressant" has also never meant "induces long term state of depression".
  - openasocket 10y ago
    depressants inhibit neurotransmission, and the prevailing theory as to the biologic foundations of depression is decreased availability of certain neurotransmitters. I'm not saying depressants can cause or induce depression, but they certainly don't help. On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse.
    - devishard 10y ago
      > I'm not saying depressants can cause or induce depression, but they certainly don't help. Studies say otherwise.[1][2] > On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse. Reduced affect is brought up all the time when talking about various things and people go "Oh noes! Reduced affect!" which only goes to show that they have no idea what the phrase means. It's not particularly negative in itself; it's only a diagnostic criteria of underlying disorders which have negative effects. Lethargy and general lack of energy are the same thing. So basically you have one negative symptom you claim ketamine will cause because it's a depressant. Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it, you should maybe consider the idea that you don't know what you're talking about and stop talking. To be clear, I'm not particularly in favor of ketamine in treatment. If you knew what you were talking about, you might have, for example, cited the most obvious side effect of ketamine which is bladder damage. Ketamine needs to be studied more, in my opinion, to find out whether the positives outweigh the negatives. But your ignorant opinion based on the etymology of "depression" is actually detracting from this conversation and doesn't help us to study it. You're just spreading misinformation for no reason except your own ego. [1] https://www.clinicaltrials.gov/ct2/show/NCT00088699 https://www.clinicaltrials.gov/ct2/show/NCT00088699 [2] https://www.nimh.nih.gov/about/director/2014/ketamine.shtml https://www.nimh.nih.gov/about/director/2014/ketamine.shtml
      - martin1975 10y ago
        I'd so try a ketamine based product, despite the fact that its regular use is for general anesthesia ... If I remember correctly even SSRIs were "accidentally" discovered by observing metabolizing effects of - and I hope someone corrects me here if I'm off - cough syrup. Dicking around with the chemistry of ketamine to make it safe and therapeutic as well as pre-cursory enough for consumption to generate the desired effect could take years though, and there still might be issues even then that would prevent it from general use.... Bit off topic - if there's one place where I am for patents, it's for pharma - takes years to find something that works, and when they finally do, it's only natural that they would want to recoup the money.
        maxerickson 10y ago
        There are clinics in the US using it to treat depression. Who knows how much scientific justification they have to do so, but they are taking patients and so on.
      - openasocket 10y ago
        I think you make some good points, though I think some of your remarks are a tad too aggressive. Some rebuttal: Your first link is to a trial on ketamine that is currently ongoing, so hasn't reported any results. The second mentions some promise in ketamine for clinical usage, but that doesn't dispute my point that depressants will exacerbate many of the symptoms of clinical depression. > Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it ... You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant.
        devishard 10y ago
        > I think you make some good points, though I think some of your remarks are a tad too aggressive. If you decide to share your opinions on things you don't know about as if you do know about them, then I'm not sure what you're expecting. Warmth and acceptance? > You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant. Yes and I will, because that's the entire point of what I'm saying. Just because something falls in the broad category of "depressant" doesn't mean it's going to make you lethargic.
    - rhizome 10y ago
      I think you're oversimplifying the concepts in service of a category error vis-a-vis depressants and depression.
    - DanBC 10y ago
      >Depressants will make those symptoms worse. Ketamine is used in a very small dose. There's plenty of research showing some beneficial effect.
      - aminorex 10y ago
        "Some" is a gross understatement of the treatment's efficacy and import in the cases where it is effective.
- fhood 10y ago
  highly addictive is a pretty serious stretch don't you think. It is definitely possible do develop a psychological dependency, but nothing like morphine, nicotine, or even caffeine.
  - darpa_escapee 10y ago
    Like the drugs you've listed, it builds a physical dependence if used frequently enough. Someone who is physically dependent will experience withdrawals in the absence of ketamine. Like those drugs, it induces a desire to consume more of the substance in many users in such a way that something like codeine does and ibuprofen doesn't. Ketamine is a dopamine reuptake inhibitor, possibly leading to some of the euphoric and reinforcing effects of the drug. Cocaine, methylphenidate and methamphetamine are examples of addictive and abused dopamine reuptake inhibitors. Addictive drugs have direct or downstream effects on the dopamine system. It also stimulates the D2 subtype of dopamine receptors.
    - spdustin 10y ago
      Edit: reply was meant for GP Ketamine primarily acts on glutamate, one of the reasons it's such an "effective" anesthetic, as the specific glutamate receptor (NMDA) it acts on is involved both in memory formation and the rather complex neurological process that leads to experiencing chronic pain. Its effect on dopamine reuptake (along with norepinephrine and serotonin), GABA potentiation, and opioid receptors means, roughly, it affects much more of the brain's chemistry than the "unwashed masses" using it are aware of. They think it's relatively safe because it wears off faster than PCP (it does) or other depressants (it does) but in reality it dramatically affects multiple systems in their bodies, with some effects building up over time to ultimately cause physical damage (like bladder wall thickening, or damage to cardiac tissues). And in the meantime, they come to relish the escape of the K-hole. At least, until they have a bad trip, because the hallucinations they have are still controlled by their own brains, and if they're having a bad time in life, their hallucinations aren't going to be helpful. What's worse, because they think it's like any other depressant, they freely combine it with Adderall. Ketamine is a cardiovascular stimulant, and mixing with Adderall has a very real risk of proving fatal. Psychological addiction causes users to disregard all these risks, even the ones the users know about, and pursue taking the drug regardless, and is no less dangerous than physical addiction. In fact, because of its effects on dopaminergic modulation and opioid receptors, there is an easy argument to be made for the addictive potential of ketamine. Further, it's important to understand: rats will self-dose with it, humans rate the high they get from low doses of it as being likable and causing them to want more, daily users often go through withdrawal symptoms and experience cravings after they stop using, and users rapidly develop a tolerance for it - all of these are metrics used to determine how addictive something is. Which is to say, in the case of Ketamine, quite. So, no, it's not a stretch at all. That doesn't limit its usefulness in clinical settings, but do not fool yourself or anyone else that it's not addictive.
- pierrec 10y ago
  "not to mention you're giving a _depressant_ to a depressed person" Heh, these concepts are unrelated to the point that this statement could make a decent joke. As a rough example, it's on the level of "not to mention that you're installing a clock application on a computer that's already overclocked".
  - tgb 10y ago
    Love the example. In reminded of snopes' take on the "the car called Nova failed to sell in Mexico because 'no va' means 'it doesn't go' in Spanish" myth. Their example was of Americans not wanting to buy a car called "Notable" because it had no table.
    - 50CNT 10y ago
      Or was "not able".
  - openasocket 10y ago
    At the risk of making an appeal to authority, I got that quote from a clinical psychologist, referring to the effect of alcohol on clinical depression. See my other comment for an explanation.
    - pierrec 10y ago
      I see, it makes more sense when you make it more explicit. But then I also have an appeal to authority: the majority of drugs prescribed against depression also happen to be depressants. And sometimes it works, though they all tend to have addiction and habituation potentials as well. I would say the psychologist you're quoting is raising a point that goes against the mainstream, which is not necessarily bad of course, but the phrase in itself remains a (somewhat misleading) play on words.
      - openasocket 10y ago
        >the majority of drugs prescribed against depression also happen to be depressants Can you give a source for that, and some examples? I couldn't find anything (googling "antidepressant depressant" is about as helpful as you'd think). I'd still argue that the effects of depressants (the inhibition of neurotransmission) are in and of themselves not helpful for people depression. I agree my phrasing was a bit confusing, I tend to value poignancy over explicitness :)
- pantalaimon 10y ago
  > Ketamine especially would not be a good anti-depressant pill, because it is highly addictive SSRI withdrawl effects last up to a month whereas Ketamine once a month produces no such effects. So the current therapy for depression is more addictive, by design, than Ketamine.
  - kps 10y ago
    Just a note: in English, “by design” is an idiomatic construction that means “deliberately”. You probably want something like “by nature”.
    - aminorex 10y ago
      By design seems more correct, given the pecuniary interests of the designers.
- devishard 10y ago
  > not to mention you're giving a _depressant_ to a depressed person That's about as terrible as giving _ham_ to a hamster.
- soundwave106 10y ago
  It is right to be skeptical of using the actual compound with its negatives (for instance, the hallucinogenic / dissociative properties of ketamine and the neurotransmitter depletion of MDMA.) However, it is possible that illegal recreational compounds can shed some light on body chemistry, and I think that's what happened here. The "ketamine is an antidepressant" story has been around for a while. It was considered kind of a deal because everything about depression previously dealt with serotonin, and ketamine clearly has nothing to do with serotonin. Consequently there's people working on compounds with similar actions, but without ketamine's ill effects. The closest one I know to production is this one: https://en.wikipedia.org/wiki/Rapastinel https://en.wikipedia.org/wiki/Rapastinel Which, as a Phase III "breakthrough candidate", still has a long way to go, of course. This new study is significant, though, if it is not the NMDA receptor that is really creating ketamine's anti-depressant effects. It may allow for alternate compounds to be explored beyond even what is being worked on now.
deleted 10y ago
[deleted]
skrowl 10y ago
While interesting, I'm not sure what to do with this information. I guess we can keep this in mind the next time we see some depressed horses?
- nindalf 10y ago
  Ketamine is consumed by humans too.
- rincebrain 10y ago
  If you were unaware, ketamine and similar drugs have been used in humans for their incidental antidepressant effects, which has been getting some level of traction for investigation of late. Discovering which metabolite was responsible for this in mice is a useful step toward trying said metabolite in humans, since the cognitive effects of attempting some of the things that they did to the mice would be...unpleasant, to say the least, if not outright unethical. In addition, finding the component responsible will permit them to utilize it as a treatment without any of the concerns , difficulties, or stigma associated with being given an IV of a psychedelic addictive substance periodically.
  - tptacek 10y ago
    People who know that ketamine is "horse tranquilizer" uniformly also know that it's used in humans. That's simply a troll comment.
- llamataboot 10y ago
  Ketamine is an extraordinarily safe anesthetic and so is often used in vulnerable human populations as well.
  - antihero 10y ago
    I wonder, if you had to for some reason do field surgery at a rave, whether you could go round grabbing baggies off of people in order to dose them enough to operate.
rm_-rf_slash 10y ago
The recent emergence of studies suggesting psychedelics as a novel means of treating depression and other mental illnesses is a double-edged blade: the sheer capability of drugs like LSD and psilocybin and ketamine to hard-reset the brain's pathways is a huge leap from the accepted style of treatment that often boils down to "Take these pills, check in each week, maybe you'll feel better in a month or two." However, it also gives people the false impression that all they need to do is chew on some shrooms and listen to the Grateful Dead for a couple of hours and suddenly they will be free of all addiction and depression forever. Every time a study like this comes out there is a predictable pattern in patients' depression scores: immediately after psychedelic treatment, depression signs plunge, wade around the low end for a while, then steadily creep back up. With the exception of people whose brains simply do not work as they should (I have a friend who is chronically depressed because his body can't produce enough serotonin even with antidepressants), depression is often as influenced by external factors as internal ones. A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world. Discoveries like these are always helpful towards understanding the brain and how to formulate effective treatment, but in the end, mental health will always be vastly more complex and harder to cure than any physical ailment. There will never be anything close to an ibuprofen for the brain.
- RankingMember 10y ago
  > A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world. It's true that drugs won't change reality, but our interpretation and reaction to reality is what's important, and therapy/drugs can certainly change that.
  - rincebrain 10y ago
    One of the more interesting properties of ketamine that underscores your statement is its effectiveness in treating PTSD...[1] ...as well as lowering the incidence of PTSD among people who had been treated with ketamine as an anesthetic prior to a traumatic experience. [2] [3] [1] - https://www.ncbi.nlm.nih.gov/pubmed/24740528 https://www.ncbi.nlm.nih.gov/pubmed/24740528 [2] - http://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00360-1/abstract http://www.biologicalpsychiatryjournal.com/article/S0006-322... [3] - http://www.dtic.mil/get-tr-doc/pdf?AD=ADA480518 http://www.dtic.mil/get-tr-doc/pdf?AD=ADA480518
univalent 10y ago
I wish there was a good program advocating the effectiveness of Electroconvulsive therapy (and maybe some studies around harmful effects on long term usage). I've taken basically every drug on the spectrum (benzos, SSRIs, et.al.) for most of my life since I was a teenager and nothing helped as much as ECT.
- wyager 10y ago
  Doesn't even modern ECT have serious problems with memory loss side effects?
  - martin1975 10y ago
    It does. That's why it should be considered as a last resort if all else fails.
  - univalent 10y ago
    I think it varies from patient to patient. In my case, 2 separate courses of 6 treatments resulted in almost no short term memory loss.
- martin1975 10y ago
  Bit tangential but I think this can be informative for some sufferers - I've been taking zoloft for a few years now as I have (or had I should say) panic/anxiety attacks and co-morbid depression which went untreated for decades ... I inquired from my doctor about ECT, and although ECT is the cadillac of treatments, in some patients that it has not worked, to my great surprise, nicotine has had a really great effect on reducing or eliminating depression. I'm not advocating taking up smoking, although it is something worthwhile to consider if things like ECT don't help. There's probably ways nicotine can be therapeutically administered without the negative side-effects of burning tobacco.
  - intopieces 10y ago
    There is, unfortunately, a social stigma associated with the non-tobacco-smoking form of nicotine ingestion and the components to those devices (e-cigarettes) are not regulated enough for us to be fully sure of their effects.
willholloway 10y ago
S-Ketamine injected through the ear drum, into the middle ear, is currently undergoing phase III trials as a treatment for noise or infection induced tinnitus. Chronic tinnitus is currently a condition which if one were to go to the doctor and ask for a cure one would be told to get used to it as there is not much that can be done. The pace of medical and biotech advancement is increasing as the FDA has relaxed a bit and better understanding of human biology is creating cures for what once were incurable diseases. Exciting times, but not fast enough for me. The most interesting question for me these days: How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that?
- ycosynot 10y ago
  Connecting the whole world to internet brings the best returns.
- obiefernandez 10y ago
  Dammit, I got my hopes up... :( "The treatment, delivered directly into the inner ear via three injections over three days, must catch the disorder while the problem is still within the ear, before the brain has begun overcompensating for the loss of hearing. Once that happens, no amount of adjustment to the receptors on the auditory nerves will do any good. Because it is not known when that transition from ear to brain occurs, one of the current trials, of 300 European patients, is specifically testing tinnitus sufferers who have developed the condition no more than three months prior to treatment. The other, a study of 330 North American patients, is investigating a therapy within one year post-trauma. Preliminary results suggest that S-ketamine is effective beyond three months, but declines in effectiveness within a year of the initial trauma, so later stages of the trial are being refocused on the four- to six-month time frame. The trials will be completed at the end of this year, and Auris hopes to submit to the US Food and Drug Administration (FDA) for approval in the summer of 2016."
CPLX 10y ago
> How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that? Have you considered multiplying by 100? Note that the preceding sentence also has the advantage of having a real actual verb in it. Though I suppose it's pointless to rail against insufferable tech buzzword-speak, or typical valley-style nonsensical 10x statements at this point. Oh well.
- smt88 10y ago
  1) "Nx" is a widely-understood, abbreviated way to write "multiply by N". You certainly understood it. Do you have an issue with abbreviations? 2) It seems like he said "10x...and then 10x" instead of "100x" as either A) an allusion to a multi-staged process, or B) a rhetorical device to emphasize the magnitude of the changes needed. Either way, it isn't exactly the same as just saying "100x". 3) Your comment has no substance and is just an attack. That's against HN rules.
- o_____________o 10y ago
  Mmm, pointless internet hostility
  - aminorex 10y ago
    Without conflict, there can be no drama.
- willholloway 10y ago
  Exponential growth doesn't happen in one discrete operation, friend. Here's some more interesting info about the trials for s-ketamine as a tinnitus treatment. The vision for the company that is trying to bring intratympanic s-ketamine to market as a tinnitus treatment was very interesting to me. The founder was looking for new uses for drugs that are currently approved and with long safety records, that could be tested on animals. I thought it was interesting criteria for a low-hanging fruit search of the problem space in medicine, considering regulatory realities as well as financial ones.
  - 10y ago

125 points by MollyR 10y ago

OK, I've been skeptical in the past about studies suggesting drugs like ketamine and MDMA could be used to treat depression. Ketamine especially would not be a good anti-depressant pill, because it is highly addictive, not to mention you're giving a _depressant_ to a depressed person. However, this result is promising. This study has claimed to have isolated the anti-depressant effect to a particular product of ketamine metabolism, and that this compound contains none of the anesthetic and addictive properties. Obviously, this is just a single study, performed on mice, but it is a promising first step towards the potential development of a new anti-depressant.

maxerickson 10y ago
Why are you reasoning from the words used to describe it? "depressant" has also never meant "induces long term state of depression".
- openasocket 10y ago
  depressants inhibit neurotransmission, and the prevailing theory as to the biologic foundations of depression is decreased availability of certain neurotransmitters. I'm not saying depressants can cause or induce depression, but they certainly don't help. On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse.
  - devishard 10y ago
    > I'm not saying depressants can cause or induce depression, but they certainly don't help. Studies say otherwise.[1][2] > On a more practical level, many people with clinical depression suffer from reduced affect, lethargy, and general lack of energy. Depressants will make those symptoms worse. Reduced affect is brought up all the time when talking about various things and people go "Oh noes! Reduced affect!" which only goes to show that they have no idea what the phrase means. It's not particularly negative in itself; it's only a diagnostic criteria of underlying disorders which have negative effects. Lethargy and general lack of energy are the same thing. So basically you have one negative symptom you claim ketamine will cause because it's a depressant. Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it, you should maybe consider the idea that you don't know what you're talking about and stop talking. To be clear, I'm not particularly in favor of ketamine in treatment. If you knew what you were talking about, you might have, for example, cited the most obvious side effect of ketamine which is bladder damage. Ketamine needs to be studied more, in my opinion, to find out whether the positives outweigh the negatives. But your ignorant opinion based on the etymology of "depression" is actually detracting from this conversation and doesn't help us to study it. You're just spreading misinformation for no reason except your own ego. [1] https://www.clinicaltrials.gov/ct2/show/NCT00088699 https://www.clinicaltrials.gov/ct2/show/NCT00088699 [2] https://www.nimh.nih.gov/about/director/2014/ketamine.shtml https://www.nimh.nih.gov/about/director/2014/ketamine.shtml
    - martin1975 10y ago
      I'd so try a ketamine based product, despite the fact that its regular use is for general anesthesia ... If I remember correctly even SSRIs were "accidentally" discovered by observing metabolizing effects of - and I hope someone corrects me here if I'm off - cough syrup. Dicking around with the chemistry of ketamine to make it safe and therapeutic as well as pre-cursory enough for consumption to generate the desired effect could take years though, and there still might be issues even then that would prevent it from general use.... Bit off topic - if there's one place where I am for patents, it's for pharma - takes years to find something that works, and when they finally do, it's only natural that they would want to recoup the money.
      - maxerickson 10y ago
        There are clinics in the US using it to treat depression. Who knows how much scientific justification they have to do so, but they are taking patients and so on.
    - openasocket 10y ago
      I think you make some good points, though I think some of your remarks are a tad too aggressive. Some rebuttal: Your first link is to a trial on ketamine that is currently ongoing, so hasn't reported any results. The second mentions some promise in ketamine for clinical usage, but that doesn't dispute my point that depressants will exacerbate many of the symptoms of clinical depression. > Given that it's a party drug taken in much-higher-than-clinical doses at raves where people dance for hours on it ... You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant.
      - devishard 10y ago
        > I think you make some good points, though I think some of your remarks are a tad too aggressive. If you decide to share your opinions on things you don't know about as if you do know about them, then I'm not sure what you're expecting. Warmth and acceptance? > You can make the same point about alcohol: people routinely ingest large amounts of alcohol and can still engage in lots of physical activity, despite it being a depressant. Yes and I will, because that's the entire point of what I'm saying. Just because something falls in the broad category of "depressant" doesn't mean it's going to make you lethargic.
  - rhizome 10y ago
    I think you're oversimplifying the concepts in service of a category error vis-a-vis depressants and depression.
  - DanBC 10y ago
    >Depressants will make those symptoms worse. Ketamine is used in a very small dose. There's plenty of research showing some beneficial effect.
    - aminorex 10y ago
      "Some" is a gross understatement of the treatment's efficacy and import in the cases where it is effective.
fhood 10y ago
highly addictive is a pretty serious stretch don't you think. It is definitely possible do develop a psychological dependency, but nothing like morphine, nicotine, or even caffeine.
- darpa_escapee 10y ago
  Like the drugs you've listed, it builds a physical dependence if used frequently enough. Someone who is physically dependent will experience withdrawals in the absence of ketamine. Like those drugs, it induces a desire to consume more of the substance in many users in such a way that something like codeine does and ibuprofen doesn't. Ketamine is a dopamine reuptake inhibitor, possibly leading to some of the euphoric and reinforcing effects of the drug. Cocaine, methylphenidate and methamphetamine are examples of addictive and abused dopamine reuptake inhibitors. Addictive drugs have direct or downstream effects on the dopamine system. It also stimulates the D2 subtype of dopamine receptors.
  - spdustin 10y ago
    Edit: reply was meant for GP Ketamine primarily acts on glutamate, one of the reasons it's such an "effective" anesthetic, as the specific glutamate receptor (NMDA) it acts on is involved both in memory formation and the rather complex neurological process that leads to experiencing chronic pain. Its effect on dopamine reuptake (along with norepinephrine and serotonin), GABA potentiation, and opioid receptors means, roughly, it affects much more of the brain's chemistry than the "unwashed masses" using it are aware of. They think it's relatively safe because it wears off faster than PCP (it does) or other depressants (it does) but in reality it dramatically affects multiple systems in their bodies, with some effects building up over time to ultimately cause physical damage (like bladder wall thickening, or damage to cardiac tissues). And in the meantime, they come to relish the escape of the K-hole. At least, until they have a bad trip, because the hallucinations they have are still controlled by their own brains, and if they're having a bad time in life, their hallucinations aren't going to be helpful. What's worse, because they think it's like any other depressant, they freely combine it with Adderall. Ketamine is a cardiovascular stimulant, and mixing with Adderall has a very real risk of proving fatal. Psychological addiction causes users to disregard all these risks, even the ones the users know about, and pursue taking the drug regardless, and is no less dangerous than physical addiction. In fact, because of its effects on dopaminergic modulation and opioid receptors, there is an easy argument to be made for the addictive potential of ketamine. Further, it's important to understand: rats will self-dose with it, humans rate the high they get from low doses of it as being likable and causing them to want more, daily users often go through withdrawal symptoms and experience cravings after they stop using, and users rapidly develop a tolerance for it - all of these are metrics used to determine how addictive something is. Which is to say, in the case of Ketamine, quite. So, no, it's not a stretch at all. That doesn't limit its usefulness in clinical settings, but do not fool yourself or anyone else that it's not addictive.
pierrec 10y ago
"not to mention you're giving a _depressant_ to a depressed person" Heh, these concepts are unrelated to the point that this statement could make a decent joke. As a rough example, it's on the level of "not to mention that you're installing a clock application on a computer that's already overclocked".
- tgb 10y ago
  Love the example. In reminded of snopes' take on the "the car called Nova failed to sell in Mexico because 'no va' means 'it doesn't go' in Spanish" myth. Their example was of Americans not wanting to buy a car called "Notable" because it had no table.
  - 50CNT 10y ago
    Or was "not able".
- openasocket 10y ago
  At the risk of making an appeal to authority, I got that quote from a clinical psychologist, referring to the effect of alcohol on clinical depression. See my other comment for an explanation.
  - pierrec 10y ago
    I see, it makes more sense when you make it more explicit. But then I also have an appeal to authority: the majority of drugs prescribed against depression also happen to be depressants. And sometimes it works, though they all tend to have addiction and habituation potentials as well. I would say the psychologist you're quoting is raising a point that goes against the mainstream, which is not necessarily bad of course, but the phrase in itself remains a (somewhat misleading) play on words.
    - openasocket 10y ago
      >the majority of drugs prescribed against depression also happen to be depressants Can you give a source for that, and some examples? I couldn't find anything (googling "antidepressant depressant" is about as helpful as you'd think). I'd still argue that the effects of depressants (the inhibition of neurotransmission) are in and of themselves not helpful for people depression. I agree my phrasing was a bit confusing, I tend to value poignancy over explicitness :)
pantalaimon 10y ago
> Ketamine especially would not be a good anti-depressant pill, because it is highly addictive SSRI withdrawl effects last up to a month whereas Ketamine once a month produces no such effects. So the current therapy for depression is more addictive, by design, than Ketamine.
- kps 10y ago
  Just a note: in English, “by design” is an idiomatic construction that means “deliberately”. You probably want something like “by nature”.
  - aminorex 10y ago
    By design seems more correct, given the pecuniary interests of the designers.
devishard 10y ago
> not to mention you're giving a _depressant_ to a depressed person That's about as terrible as giving _ham_ to a hamster.
soundwave106 10y ago
It is right to be skeptical of using the actual compound with its negatives (for instance, the hallucinogenic / dissociative properties of ketamine and the neurotransmitter depletion of MDMA.) However, it is possible that illegal recreational compounds can shed some light on body chemistry, and I think that's what happened here. The "ketamine is an antidepressant" story has been around for a while. It was considered kind of a deal because everything about depression previously dealt with serotonin, and ketamine clearly has nothing to do with serotonin. Consequently there's people working on compounds with similar actions, but without ketamine's ill effects. The closest one I know to production is this one: https://en.wikipedia.org/wiki/Rapastinel https://en.wikipedia.org/wiki/Rapastinel Which, as a Phase III "breakthrough candidate", still has a long way to go, of course. This new study is significant, though, if it is not the NMDA receptor that is really creating ketamine's anti-depressant effects. It may allow for alternate compounds to be explored beyond even what is being worked on now.

deleted 10y ago

[deleted]

skrowl 10y ago

While interesting, I'm not sure what to do with this information. I guess we can keep this in mind the next time we see some depressed horses?

nindalf 10y ago
Ketamine is consumed by humans too.
rincebrain 10y ago
If you were unaware, ketamine and similar drugs have been used in humans for their incidental antidepressant effects, which has been getting some level of traction for investigation of late. Discovering which metabolite was responsible for this in mice is a useful step toward trying said metabolite in humans, since the cognitive effects of attempting some of the things that they did to the mice would be...unpleasant, to say the least, if not outright unethical. In addition, finding the component responsible will permit them to utilize it as a treatment without any of the concerns , difficulties, or stigma associated with being given an IV of a psychedelic addictive substance periodically.
- tptacek 10y ago
  People who know that ketamine is "horse tranquilizer" uniformly also know that it's used in humans. That's simply a troll comment.
llamataboot 10y ago
Ketamine is an extraordinarily safe anesthetic and so is often used in vulnerable human populations as well.
- antihero 10y ago
  I wonder, if you had to for some reason do field surgery at a rave, whether you could go round grabbing baggies off of people in order to dose them enough to operate.

rm_-rf_slash 10y ago

The recent emergence of studies suggesting psychedelics as a novel means of treating depression and other mental illnesses is a double-edged blade: the sheer capability of drugs like LSD and psilocybin and ketamine to hard-reset the brain's pathways is a huge leap from the accepted style of treatment that often boils down to "Take these pills, check in each week, maybe you'll feel better in a month or two." However, it also gives people the false impression that all they need to do is chew on some shrooms and listen to the Grateful Dead for a couple of hours and suddenly they will be free of all addiction and depression forever. Every time a study like this comes out there is a predictable pattern in patients' depression scores: immediately after psychedelic treatment, depression signs plunge, wade around the low end for a while, then steadily creep back up. With the exception of people whose brains simply do not work as they should (I have a friend who is chronically depressed because his body can't produce enough serotonin even with antidepressants), depression is often as influenced by external factors as internal ones. A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world. Discoveries like these are always helpful towards understanding the brain and how to formulate effective treatment, but in the end, mental health will always be vastly more complex and harder to cure than any physical ailment. There will never be anything close to an ibuprofen for the brain.

RankingMember 10y ago
> A spectacular drug trip won't change the reality of having a death in the family, not being able to find a job after being laid off at 45, or simply the stress of the modern, always-on world. It's true that drugs won't change reality, but our interpretation and reaction to reality is what's important, and therapy/drugs can certainly change that.
- rincebrain 10y ago
  One of the more interesting properties of ketamine that underscores your statement is its effectiveness in treating PTSD...[1] ...as well as lowering the incidence of PTSD among people who had been treated with ketamine as an anesthetic prior to a traumatic experience. [2] [3] [1] - https://www.ncbi.nlm.nih.gov/pubmed/24740528 https://www.ncbi.nlm.nih.gov/pubmed/24740528 [2] - http://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00360-1/abstract http://www.biologicalpsychiatryjournal.com/article/S0006-322... [3] - http://www.dtic.mil/get-tr-doc/pdf?AD=ADA480518 http://www.dtic.mil/get-tr-doc/pdf?AD=ADA480518

univalent 10y ago

I wish there was a good program advocating the effectiveness of Electroconvulsive therapy (and maybe some studies around harmful effects on long term usage). I've taken basically every drug on the spectrum (benzos, SSRIs, et.al.) for most of my life since I was a teenager and nothing helped as much as ECT.

wyager 10y ago
Doesn't even modern ECT have serious problems with memory loss side effects?
- martin1975 10y ago
  It does. That's why it should be considered as a last resort if all else fails.
- univalent 10y ago
  I think it varies from patient to patient. In my case, 2 separate courses of 6 treatments resulted in almost no short term memory loss.
martin1975 10y ago
Bit tangential but I think this can be informative for some sufferers - I've been taking zoloft for a few years now as I have (or had I should say) panic/anxiety attacks and co-morbid depression which went untreated for decades ... I inquired from my doctor about ECT, and although ECT is the cadillac of treatments, in some patients that it has not worked, to my great surprise, nicotine has had a really great effect on reducing or eliminating depression. I'm not advocating taking up smoking, although it is something worthwhile to consider if things like ECT don't help. There's probably ways nicotine can be therapeutically administered without the negative side-effects of burning tobacco.
- intopieces 10y ago
  There is, unfortunately, a social stigma associated with the non-tobacco-smoking form of nicotine ingestion and the components to those devices (e-cigarettes) are not regulated enough for us to be fully sure of their effects.

willholloway 10y ago

S-Ketamine injected through the ear drum, into the middle ear, is currently undergoing phase III trials as a treatment for noise or infection induced tinnitus. Chronic tinnitus is currently a condition which if one were to go to the doctor and ask for a cure one would be told to get used to it as there is not much that can be done. The pace of medical and biotech advancement is increasing as the FDA has relaxed a bit and better understanding of human biology is creating cures for what once were incurable diseases. Exciting times, but not fast enough for me. The most interesting question for me these days: How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that?

ycosynot 10y ago
Connecting the whole world to internet brings the best returns.
obiefernandez 10y ago
Dammit, I got my hopes up... :( "The treatment, delivered directly into the inner ear via three injections over three days, must catch the disorder while the problem is still within the ear, before the brain has begun overcompensating for the loss of hearing. Once that happens, no amount of adjustment to the receptors on the auditory nerves will do any good. Because it is not known when that transition from ear to brain occurs, one of the current trials, of 300 European patients, is specifically testing tinnitus sufferers who have developed the condition no more than three months prior to treatment. The other, a study of 330 North American patients, is investigating a therapy within one year post-trauma. Preliminary results suggest that S-ketamine is effective beyond three months, but declines in effectiveness within a year of the initial trauma, so later stages of the trial are being refocused on the four- to six-month time frame. The trials will be completed at the end of this year, and Auris hopes to submit to the US Food and Drug Administration (FDA) for approval in the summer of 2016."

CPLX 10y ago

> How can we 10x the number of dollars and scientists engaged in medical research, and then 10x that? Have you considered multiplying by 100? Note that the preceding sentence also has the advantage of having a real actual verb in it. Though I suppose it's pointless to rail against insufferable tech buzzword-speak, or typical valley-style nonsensical 10x statements at this point. Oh well.

smt88 10y ago
1) "Nx" is a widely-understood, abbreviated way to write "multiply by N". You certainly understood it. Do you have an issue with abbreviations? 2) It seems like he said "10x...and then 10x" instead of "100x" as either A) an allusion to a multi-staged process, or B) a rhetorical device to emphasize the magnitude of the changes needed. Either way, it isn't exactly the same as just saying "100x". 3) Your comment has no substance and is just an attack. That's against HN rules.
o_____________o 10y ago
Mmm, pointless internet hostility
- aminorex 10y ago
  Without conflict, there can be no drama.
willholloway 10y ago
Exponential growth doesn't happen in one discrete operation, friend. Here's some more interesting info about the trials for s-ketamine as a tinnitus treatment. The vision for the company that is trying to bring intratympanic s-ketamine to market as a tinnitus treatment was very interesting to me. The founder was looking for new uses for drugs that are currently approved and with long safety records, that could be tested on animals. I thought it was interesting criteria for a low-hanging fruit search of the problem space in medicine, considering regulatory realities as well as financial ones.
- 10y ago