25 ms·

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms [pdf]

227 points by dtawfik1 9y ago

DenisM 9y ago
From the abstract: [...] Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. [...]
- deleted 9y ago
  [deleted]
- dtawfik1 9y ago
  yeah, very interesting
- discordance 9y ago
  N=19 is a very small sample size. I would be careful forming opinions based on this study.
  - jessaustin 9y ago
    Yes it is much better to enjoy psilocybin oneself.
  - pizza 9y ago
    even if it were e.g. sixteen or seventeen, for all of them to report lessened depression a week after is a fairly strong finding, at least enough to merit someone else attempting to reproduce the research. present depression medication barely works better than placebo
    - xzel 9y ago
      Yes. I think if you put you and your parent comment together it forms a good synthesis of how to approach the results of this study.
    - DanBC 9y ago
      > present depression medication barely works better than placebo That depends on quite a few things, and so far none of the psilocybin treatments are controlling for those. It's possible (likely, even) that if psilocybin is approved for treatment and used as often as other meds we'll see effectiveness plummet.
  - anythingnonidin 9y ago
    Please read 'A Prevalent Misconception About Sample Size, Statistical Significance, and Clinical Importance' http://www.joponline.org/doi/abs/10.1902/jop.1972.43.3.181?journalCode=jop http://www.joponline.org/doi/abs/10.1902/jop.1972.43.3.181?j...
    - cJ0th 9y ago
      Perhaps I am a bit dense but I still don't see why small sample sizes aren't problematic. If the data source we tap is valid (i.e.: it does give us the information that we really need) then we need a big sample size to gain precision. If, otoh, the data is not valid in the first place then neither a small nor a big sample size are helpful.
      - jonex 9y ago
        Sample size is relevant to which opinions to form. But I think the GP wanted to point out that just having a small sample size does not invalidate the results of a study given equal confidence scores. It's a common misconception that the conclusions of a large study always are more trustworthy than from a small study. A larger study will however be able to detect smaller effects and will, as you mention, provide more precision.
      - Obi_Juan_Kenobi 9y ago
        The issue is effect size. If the effect is large or easily detected, then you don't need many individuals to determine significant differences in the broader population. What you seem to be referring to is whether or not a sample is representative of a population, which is indeed a critical factor in statistics, but not really related to the issue here.
ComputerGuru 9y ago
Before self-medicating based on this combined with a self-diagnosis, consider that LSD and psilocybin have a nasty tendency of triggering latent psychological conditions if not taken in the appropriate dosage and in a controlled environment. [ref: http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/publishing.nsf/Content/FE16C454A782A8AFCA2575BE002044D0/$File/mono71.pdf http://www.nationaldrugstrategy.gov.au/internet/drugstrategy... ]
- dtawfik1 9y ago
  Definitely. Probably is a good resource for psychiatrist as a treatment strategy rather than a protocol for patients to self direct.
  - wallace_f 9y ago
    I can swear I came across a study I found, I believe, on Erowid, which noted this link had a lower instance of increased mental illness than religious "meccas" do. In light of that evidence, it's entirely possible the human experience itself, and not some more mechanistic action or first order effect of the drug, cause the increase in mental illness. I'm trying to find this source, but am coming up short and on mobile, but will look into it later.
- lawpoop 9y ago
  Actually, I think this is more a risk of marijuana, which in the US, is prescribable in several states, legal in a few, and decriminalized in most. Which is not to say that I encourage recklessness with psychedelics, but that forasmuch as that is a concern with LSD or psilocybin, we're got bigger fish on our hands. Marijuana is much more available than either of those.
- cheshire_cat 9y ago
  I'd definitely advise anyone thinking about this to do their research but the risk doesn't seem to be as large as often suggested. There was a large US study that showed no correlation between lifetime psychedelic use and mental health problems. "[...] lifetime use of LSD, psilocybin, mescaline, or peyote, or past year use of LSD, was not associated with a higher rate of mental health problems." https://www.nature.com/news/no-link-found-between-psychedelics-and-psychosis-1.16968 https://www.nature.com/news/no-link-found-between-psychedeli... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/
trgv 9y ago
Assuming that psilocybin is effective at treating depression, I find myself wondering whether actual conscious experience (that is, being high) is an essential part of its effectiveness or not. To put this another way, imagine someone takes whatever dose of psilocybin and then is rendered unconsciousness until the perceptual effects wear off. Will there be any difference in its effectiveness as a treatment for depression?
- evincarofautumn 9y ago
  I would assume so, that it’d be akin to a strong one-shot antidepressant. Psilocybin is quickly metabolised to psilocin, which binds to serotonin receptors. It might be more of a risk for a bad trip, though, unless you have good dream control. Also, you’d definitely need to be rendered unconscious, haha—I can’t imagine trying to sleep naturally on mushrooms, although when I take them I always have the most beautifully restful sleep after coming down.
  - DigitalJack 9y ago
    Propofol would do the trick (in a clinical setting).
    - SomeStupidPoint 9y ago
      Putting someone under while on drugs that typically render it hard to sleep without disrupting the drugs seems considerably harder and riskier than keeping the trip a safe experience by having experienced psychiatrists and antipsychs on hand.
    - amigoingtodie 9y ago
      Michael Jackson disagrees.
- mabbo 9y ago
  To refine your question further[0]: is this an effect of the psychological experience of tripping on mushrooms, or is this a physiological effect of the drug itself? In either case, it may explain some habitual drugs users who are actually self-medicating. It could be that in a few years, they're doing the exact same thing but with a prescription to make it all morally upstanding. [0]Correct me if I'm misunderstanding.
adammunich 9y ago
Anecdotally, I've seen psilocybin to be an excellent assistant, but not treatment per say, for depression. It can temporarily free people from negative thought patterns; but lasting change only comes from persistent self-reflection and actualization.
- uoaei 9y ago
  Anecdotally, this is precisely my experience. It'll start the engine, but you have to navigate the course.
rubatuga 9y ago
I think it would make a trip to a psychologists office much more exciting
debarshri 9y ago
My girlfriend has treatment resistant depression. Most of her life doctors prescribed SSRI based drugs which didn't really work. A lot of money was also spent on psychiatrist for CBT. Based on a youtube videos and blogpost, read about 5HTP. I think 5htp supplements really works in cases where depression is genetic or the depression exists since childhood, where the cause of depression is not known. You can actually see the result and change in personality within few week. I think 5HTP should be the first medication before any other psychoactive medications are consumed.
- jonnycomputer 9y ago
  Depression is such a broad spectrum disorder (or put another way, a highly variable cluster of symptoms), that its hard to generalize in any way.
- pgt 9y ago
  Beware that 5HTP can cause mitral heart valve damage due to accumulated serotonin in the periphery. Combine with green tea extract (EGCG) to reduce your risk.
beagle3 9y ago
Is Psilocybin and/or Ayahuasaca and/or any other DMT source legal anywhere in the world? I would expect at least _some_ places make it legal, possibly have hundreds/thousands of years of experience that might be interesting to read alongside modern studies.
- atom-morgan 9y ago
  I believe Psilocybin is legal enough (decriminalized?) to purchase in Amsterdam right? I remember watching a Vice piece on truffles.
  - hellofunk 9y ago
    Mushrooms were made illegal in the netherlands a few years ago, but "magic truffles" are a loophole in the law because they are not mushrooms, so they are still for sale. It's a bid of a shady distinction.
  - anythingnonidin 9y ago
    See also: https://psychedelicsociety.org.uk/experience-weekends https://psychedelicsociety.org.uk/experience-weekends (Magic truffle experience retreat in Amsterdam)
- noahdesu 9y ago
  I believe that Psilocybin is legal in Jamaica, see https://www.mycomeditations.com/ https://www.mycomeditations.com/. Since it would seem that large numbers of people visit South America to attend Ayahuasaca retreats, one may assume it is legal there. And some religious exemptions exist for both Ayahuasaca and Peyote in the U.S., but even this may be a bit fuzzy as this certainly isn't widely advertised. One may also purchase legally, in all but a few U.S. states, Psilocybin spores; they become illegal once grown.
  - alpine_glass 9y ago
    I've attended a couple ayahuasca ceremonies in the US. The first was very a peaceful affair. The second was not. There was yelling, screaming, the energy was all over the place. At moments, it felt very chaotic, like the top was going to blow off the whole thing. The facilitators (shamans) did an amazing job of holding things together, but that doesn't mean that I didn't experience some very intense waves of paranoia while all of this was going on. We were in a somewhat secluded place, but maybe not secluded enough to have made the screams inaudible to our closest neighbor. It was a rough evening for everyone.
avodonosov 9y ago
Heroin, BTW, helps from cough. https://en.wikipedia.org/wiki/Heroin#History https://en.wikipedia.org/wiki/Heroin#History > From 1898 through to 1910, diamorphine was marketed under the trademark name Heroin as a non-addictive morphine substitute and cough suppressant.
- snvzz 9y ago
  >heroin >non-addictive I'm confused.
  - deleted 9y ago
    [deleted]
  - anythingnonidin 9y ago
    Somewhat interestingly/surprisingly, heroin is in the same ballpark of addictiveness as alcohol, as measured by the percent of people who use it 1+ times outside of a medical setting who end up becoming dependent. Alcohol: 15-23% Heroin: 23% https://www.ncbi.nlm.nih.gov/pubmed/21145178 https://www.ncbi.nlm.nih.gov/pubmed/21145178
  - askvictor 9y ago
    > marketed as Anti depressants are addictive in the classical sense. But the pharmaceutical companies don't call it 'withdrawl' but rather 'discontinuation syndrome' when you're coming off them. Looks like not much as changed in 100 odd years of pharmaceutical marketing.
    - DanBC 9y ago
      > Anti depressants are addictive in the classical sense. No, they are not. addiction in the classic sense requires: 1) pre-occupation and seeking 2) tolerance 3) dependence Anti depressant meds don't have any of these. But even if you call discontinuation effects "dependence" you still don't have tolerance or drug seeking and preoccupation.
gt_ 9y ago
I still don't have the words to explain how, but I insist that psilocybin played a major role in the most successful period of my life. I am generally a highly skeptical person and remain a little frustrated that I can't articulate better such an impactful correlation.
- anythingnonidin 9y ago
  Can you share any more details?
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anythingnonidin 9y ago
It is absolutely shocking to me that research into psychedelics isn't swamped with funding. I'd imagine that some wealthy people must find this stuff extremely intriguing - Yuri Milner is spending $100 million on space exploration, and a psilocybin phase 3 research trial needs ~$10 million and finds it really hard to raise money? Psychedelics have extremely high therapeutic potential, and are also just interesting in a similar same way as space exploration is interesting.
- diogenescynic 9y ago
  >It is absolutely shocking to me that research into psychedelics isn't swamped with funding. I find it more shocking that we as a society put up with it. All the pharmaceutical companies would much rather find synthetic alternatives they can patent/control. Follow the money, as always, and it makes perfect sense.
  - anythingnonidin 9y ago
    > I find it more shocking that we as a society put up with it. Great point.
  - sannee 9y ago
    > I find it more shocking that we as a society put up with it. All the pharmaceutical companies would much rather find synthetic alternatives they can patent/control. Follow the money, as always, and it makes perfect sense. Why are not pharmaceutical companies pushing synthetic psychedelics then? The whole {P,T}IHKAL is full of them, it surely isn't a large problem to cook up another variant to patent.
    - anythingnonidin 9y ago
      Good question. My guess at first pass is that {P,T}IHKAL has explored the easy search space? But, I'm not very certain here. Also, the Usona Institute had a job posting for a psychedelic chemist doing just that earlier this year. They are the group supporting the psilocybin phase 3 trials.
lighttower 9y ago
What makes this go into Nature rather than a regular medical journal?

227 points by dtawfik1 9y ago

From the abstract: [...] Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. [...]

deleted 9y ago
[deleted]
dtawfik1 9y ago
yeah, very interesting
discordance 9y ago
N=19 is a very small sample size. I would be careful forming opinions based on this study.
- jessaustin 9y ago
  Yes it is much better to enjoy psilocybin oneself.
- pizza 9y ago
  even if it were e.g. sixteen or seventeen, for all of them to report lessened depression a week after is a fairly strong finding, at least enough to merit someone else attempting to reproduce the research. present depression medication barely works better than placebo
  - xzel 9y ago
    Yes. I think if you put you and your parent comment together it forms a good synthesis of how to approach the results of this study.
  - DanBC 9y ago
    > present depression medication barely works better than placebo That depends on quite a few things, and so far none of the psilocybin treatments are controlling for those. It's possible (likely, even) that if psilocybin is approved for treatment and used as often as other meds we'll see effectiveness plummet.
- anythingnonidin 9y ago
  Please read 'A Prevalent Misconception About Sample Size, Statistical Significance, and Clinical Importance' http://www.joponline.org/doi/abs/10.1902/jop.1972.43.3.181?journalCode=jop http://www.joponline.org/doi/abs/10.1902/jop.1972.43.3.181?j...
  - cJ0th 9y ago
    Perhaps I am a bit dense but I still don't see why small sample sizes aren't problematic. If the data source we tap is valid (i.e.: it does give us the information that we really need) then we need a big sample size to gain precision. If, otoh, the data is not valid in the first place then neither a small nor a big sample size are helpful.
    - jonex 9y ago
      Sample size is relevant to which opinions to form. But I think the GP wanted to point out that just having a small sample size does not invalidate the results of a study given equal confidence scores. It's a common misconception that the conclusions of a large study always are more trustworthy than from a small study. A larger study will however be able to detect smaller effects and will, as you mention, provide more precision.
    - Obi_Juan_Kenobi 9y ago
      The issue is effect size. If the effect is large or easily detected, then you don't need many individuals to determine significant differences in the broader population. What you seem to be referring to is whether or not a sample is representative of a population, which is indeed a critical factor in statistics, but not really related to the issue here.

ComputerGuru 9y ago

Before self-medicating based on this combined with a self-diagnosis, consider that LSD and psilocybin have a nasty tendency of triggering latent psychological conditions if not taken in the appropriate dosage and in a controlled environment. [ref: http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/publishing.nsf/Content/FE16C454A782A8AFCA2575BE002044D0/$File/mono71.pdf http://www.nationaldrugstrategy.gov.au/internet/drugstrategy... ]

dtawfik1 9y ago
Definitely. Probably is a good resource for psychiatrist as a treatment strategy rather than a protocol for patients to self direct.
- wallace_f 9y ago
  I can swear I came across a study I found, I believe, on Erowid, which noted this link had a lower instance of increased mental illness than religious "meccas" do. In light of that evidence, it's entirely possible the human experience itself, and not some more mechanistic action or first order effect of the drug, cause the increase in mental illness. I'm trying to find this source, but am coming up short and on mobile, but will look into it later.
lawpoop 9y ago
Actually, I think this is more a risk of marijuana, which in the US, is prescribable in several states, legal in a few, and decriminalized in most. Which is not to say that I encourage recklessness with psychedelics, but that forasmuch as that is a concern with LSD or psilocybin, we're got bigger fish on our hands. Marijuana is much more available than either of those.
cheshire_cat 9y ago
I'd definitely advise anyone thinking about this to do their research but the risk doesn't seem to be as large as often suggested. There was a large US study that showed no correlation between lifetime psychedelic use and mental health problems. "[...] lifetime use of LSD, psilocybin, mescaline, or peyote, or past year use of LSD, was not associated with a higher rate of mental health problems." https://www.nature.com/news/no-link-found-between-psychedelics-and-psychosis-1.16968 https://www.nature.com/news/no-link-found-between-psychedeli... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747247/

trgv 9y ago

Assuming that psilocybin is effective at treating depression, I find myself wondering whether actual conscious experience (that is, being high) is an essential part of its effectiveness or not. To put this another way, imagine someone takes whatever dose of psilocybin and then is rendered unconsciousness until the perceptual effects wear off. Will there be any difference in its effectiveness as a treatment for depression?

evincarofautumn 9y ago
I would assume so, that it’d be akin to a strong one-shot antidepressant. Psilocybin is quickly metabolised to psilocin, which binds to serotonin receptors. It might be more of a risk for a bad trip, though, unless you have good dream control. Also, you’d definitely need to be rendered unconscious, haha—I can’t imagine trying to sleep naturally on mushrooms, although when I take them I always have the most beautifully restful sleep after coming down.
- DigitalJack 9y ago
  Propofol would do the trick (in a clinical setting).
  - SomeStupidPoint 9y ago
    Putting someone under while on drugs that typically render it hard to sleep without disrupting the drugs seems considerably harder and riskier than keeping the trip a safe experience by having experienced psychiatrists and antipsychs on hand.
  - amigoingtodie 9y ago
    Michael Jackson disagrees.
mabbo 9y ago
To refine your question further[0]: is this an effect of the psychological experience of tripping on mushrooms, or is this a physiological effect of the drug itself? In either case, it may explain some habitual drugs users who are actually self-medicating. It could be that in a few years, they're doing the exact same thing but with a prescription to make it all morally upstanding. [0]Correct me if I'm misunderstanding.

adammunich 9y ago

Anecdotally, I've seen psilocybin to be an excellent assistant, but not treatment per say, for depression. It can temporarily free people from negative thought patterns; but lasting change only comes from persistent self-reflection and actualization.

uoaei 9y ago
Anecdotally, this is precisely my experience. It'll start the engine, but you have to navigate the course.

rubatuga 9y ago

I think it would make a trip to a psychologists office much more exciting

debarshri 9y ago

My girlfriend has treatment resistant depression. Most of her life doctors prescribed SSRI based drugs which didn't really work. A lot of money was also spent on psychiatrist for CBT. Based on a youtube videos and blogpost, read about 5HTP. I think 5htp supplements really works in cases where depression is genetic or the depression exists since childhood, where the cause of depression is not known. You can actually see the result and change in personality within few week. I think 5HTP should be the first medication before any other psychoactive medications are consumed.

jonnycomputer 9y ago
Depression is such a broad spectrum disorder (or put another way, a highly variable cluster of symptoms), that its hard to generalize in any way.
pgt 9y ago
Beware that 5HTP can cause mitral heart valve damage due to accumulated serotonin in the periphery. Combine with green tea extract (EGCG) to reduce your risk.

beagle3 9y ago

Is Psilocybin and/or Ayahuasaca and/or any other DMT source legal anywhere in the world? I would expect at least _some_ places make it legal, possibly have hundreds/thousands of years of experience that might be interesting to read alongside modern studies.

atom-morgan 9y ago
I believe Psilocybin is legal enough (decriminalized?) to purchase in Amsterdam right? I remember watching a Vice piece on truffles.
- hellofunk 9y ago
  Mushrooms were made illegal in the netherlands a few years ago, but "magic truffles" are a loophole in the law because they are not mushrooms, so they are still for sale. It's a bid of a shady distinction.
- anythingnonidin 9y ago
  See also: https://psychedelicsociety.org.uk/experience-weekends https://psychedelicsociety.org.uk/experience-weekends (Magic truffle experience retreat in Amsterdam)
noahdesu 9y ago
I believe that Psilocybin is legal in Jamaica, see https://www.mycomeditations.com/ https://www.mycomeditations.com/. Since it would seem that large numbers of people visit South America to attend Ayahuasaca retreats, one may assume it is legal there. And some religious exemptions exist for both Ayahuasaca and Peyote in the U.S., but even this may be a bit fuzzy as this certainly isn't widely advertised. One may also purchase legally, in all but a few U.S. states, Psilocybin spores; they become illegal once grown.
- alpine_glass 9y ago
  I've attended a couple ayahuasca ceremonies in the US. The first was very a peaceful affair. The second was not. There was yelling, screaming, the energy was all over the place. At moments, it felt very chaotic, like the top was going to blow off the whole thing. The facilitators (shamans) did an amazing job of holding things together, but that doesn't mean that I didn't experience some very intense waves of paranoia while all of this was going on. We were in a somewhat secluded place, but maybe not secluded enough to have made the screams inaudible to our closest neighbor. It was a rough evening for everyone.

avodonosov 9y ago

Heroin, BTW, helps from cough. https://en.wikipedia.org/wiki/Heroin#History https://en.wikipedia.org/wiki/Heroin#History > From 1898 through to 1910, diamorphine was marketed under the trademark name Heroin as a non-addictive morphine substitute and cough suppressant.

snvzz 9y ago
>heroin >non-addictive I'm confused.
- deleted 9y ago
  [deleted]
- anythingnonidin 9y ago
  Somewhat interestingly/surprisingly, heroin is in the same ballpark of addictiveness as alcohol, as measured by the percent of people who use it 1+ times outside of a medical setting who end up becoming dependent. Alcohol: 15-23% Heroin: 23% https://www.ncbi.nlm.nih.gov/pubmed/21145178 https://www.ncbi.nlm.nih.gov/pubmed/21145178
- askvictor 9y ago
  > marketed as Anti depressants are addictive in the classical sense. But the pharmaceutical companies don't call it 'withdrawl' but rather 'discontinuation syndrome' when you're coming off them. Looks like not much as changed in 100 odd years of pharmaceutical marketing.
  - DanBC 9y ago
    > Anti depressants are addictive in the classical sense. No, they are not. addiction in the classic sense requires: 1) pre-occupation and seeking 2) tolerance 3) dependence Anti depressant meds don't have any of these. But even if you call discontinuation effects "dependence" you still don't have tolerance or drug seeking and preoccupation.

gt_ 9y ago

I still don't have the words to explain how, but I insist that psilocybin played a major role in the most successful period of my life. I am generally a highly skeptical person and remain a little frustrated that I can't articulate better such an impactful correlation.

anythingnonidin 9y ago
Can you share any more details?

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anythingnonidin 9y ago

It is absolutely shocking to me that research into psychedelics isn't swamped with funding. I'd imagine that some wealthy people must find this stuff extremely intriguing - Yuri Milner is spending $100 million on space exploration, and a psilocybin phase 3 research trial needs ~$10 million and finds it really hard to raise money? Psychedelics have extremely high therapeutic potential, and are also just interesting in a similar same way as space exploration is interesting.

diogenescynic 9y ago
>It is absolutely shocking to me that research into psychedelics isn't swamped with funding. I find it more shocking that we as a society put up with it. All the pharmaceutical companies would much rather find synthetic alternatives they can patent/control. Follow the money, as always, and it makes perfect sense.
- anythingnonidin 9y ago
  > I find it more shocking that we as a society put up with it. Great point.
- sannee 9y ago
  > I find it more shocking that we as a society put up with it. All the pharmaceutical companies would much rather find synthetic alternatives they can patent/control. Follow the money, as always, and it makes perfect sense. Why are not pharmaceutical companies pushing synthetic psychedelics then? The whole {P,T}IHKAL is full of them, it surely isn't a large problem to cook up another variant to patent.
  - anythingnonidin 9y ago
    Good question. My guess at first pass is that {P,T}IHKAL has explored the easy search space? But, I'm not very certain here. Also, the Usona Institute had a job posting for a psychedelic chemist doing just that earlier this year. They are the group supporting the psilocybin phase 3 trials.

lighttower 9y ago

What makes this go into Nature rather than a regular medical journal?