6 ms·

Welcome to year 30 of trying to prove psilocybin works for psychiatric illness. And still in the pilot stage. Even taking the data at face value, the trial can

by jtrn 1y ago

Welcome to year 30 of trying to prove psilocybin works for psychiatric illness. And still in the pilot stage. Even taking the data at face value, the trial cannot disentangle the drug effect from expectancy, psychotherapy, and statistical noise. The enormous effect sizes are almost certainly inflated, multiple-comparison error is uncontrolled, and the participant pool is highly self-selected. Until a preregistered, parallel-group, active-placebo, adequately powered study with blinded independent raters replicates these findings, their practical value for routine cancer care remains minimal. It’s so interesting to see how strong the drive to prove something works is, overriding everything. As a clinical psychologist, I would welcome this kind of therapy if it worked. But this is just sad. It’s just like listening to people claim that ivermectin can cure everything. Show me one place where this therapy is conducted by people who haven’t "drunk the Kool-Aid," and I’ll be impressed. It’s so frustrating to work with actual patients and see how much these therapies really don’t work in reality. These kinds of biased studies pop up all the time without actually panning out. I’m starting to think that people promoting therapy, giving false hope, and spending money on research like this should be viewed as corrupt and evil.

motoboi 1y ago
To better appreciate his point, read “The Control Group Is Out Of Control”: https://slatestarcodex.com/2014/04/28/the-control-group-is-out-of-control/ https://slatestarcodex.com/2014/04/28/the-control-group-is-o...
johndhi 1y ago
Why do you say the effect sizes are inflated?
- jtrn 1y ago
  Due to a small, self-selected sample, biased toward educated, prior hallucinogen users, inadequate blinding, p-hacking via uncorrected multiple tests on 17+ outcomes, and crossover design flaws that confound long-term effects with intensive therapy. Similar psychedelic therapy claims—for LSD/psilocybin alleviating cancer-related anxiety/depression—have echoed since the 1950s-1970s, yet they've never panned out into practical, scalable clinical therapies. This alone should raise a MASSIVE Bayesian statistics red flag, due to prior discount: with decades of unfulfilled hype. At this point new evidence requires extraordinary proof to update our view. If such massive effectiveness were true, it would blow what we already have out of the water, and I would be the first to promote it to my patients. But you know what they say when something sounds too good to be true.
pas 1y ago
FDA approved in 2018 for (treatment-resistant) depression? https://www.prnewswire.com/news-releases/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression-834088100.html https://www.prnewswire.com/news-releases/compass-pathways-re... ?
- jtrn 1y ago
  https://www.fda.gov/drugs/resources-information-approved-drugs/olaratumab-lartruvo https://www.fda.gov/drugs/resources-information-approved-dru... !
- Aurornis 1y ago
  That’s not what that means. Breakthrough Therapy designation means they can continue to study it with support. It does not mean it’s approved for depression.
cmrdporcupine 1y ago
Thank you for this. I am neither an advocate nor against psychedelic use in therapy but as a person who has consumed these things in the past, my own experiences make me entirely skeptical of people who put on an advocacy hat around any particular chemical. Especially psychedelics like psilocybin which are extremely unpredictable. When I was a teen a friend gave me an analogy that stuck with me. In much older computers (e.g. C64, Vic-20, etc), they'd behave "interestingly" when you mucked around with the physical circuit board or there was a fault. E.g. if something short circuited because a screw was loose in the board, or a cartridge was halfway in or a chip partially desocketed, etc. Characters would appear in random places, or the machine go through odd loops and so on. And to someone who didn't know how the machine worked, there could be a certain "magic" and a "pattern" to this. But clearly you'd be missing the point if you thought you had "enhanced" the machine this way. LSD and psilocybin are kind of like that, but for your brain. They short circuit and alter pathways. In ways that can be entertaining but you're entirely missing the point if you try to assign a higher meaning to them. Our brains are expert pattern-finding machines, and produce causes and reasons even when there are none. For some there may be value in the experience of altering the operation of your brain to get yourself out of a stuck pattern, I guess. But I am not sure the very random stochastic nature of the whole thing is ... medicinal.
landl0rd 1y ago
Most people involved in it are aware at some level that this is at best suspect and at worst a deception designed to push legalization. Same as the “health benefits of marijuana” crowd who violently deny the risks, addictive nature, potential to induce schizophrenia (temporary or permanent), tendency to make people lazy and obese, etc. Legalization has never been a question of “is this good for people?”
- jtrn 1y ago
  Plot twist, I'm for full legalization.
  - landl0rd 1y ago
    So am I, of both "hard" and "soft" drugs. I'm just pointing out the ridiculous approach some people choose to take rather than arguing from principled grounds. It's also a dangerous one: "we shouldn't use state violence against people who use X" is a moral position. "I'm going to spread lies that may lead more people to use dangerous substance X because I want to get high" is a very immoral one.
    - jtrn 1y ago
      I think I agree. But I come at it from a different angle. I only care if proposed therapies actually work, when people claim they do. I think the state has a horrendous track record of deciding what people are allowed to do with their own life. And I think drug enforcements are a waste of resources. I think almost all drugs are terrible and should never be taken. To me, all of these are simultaneously true.
      - tavavex 1y ago
        Out of curiosity, which drugs do you consider to be the exception to the "almost all drugs are terrible" line?
        jtrn 1y ago
throwaway330935 1y ago
>Welcome to year 30 of trying to prove psilocybin works for psychiatric illness. That is true, but it misses some important nuance: the war on drugs has effectively eliminated the ability for legitimate researchers to do significant research on these criminalized drugs. For example, for me personally, a mild dose of marijuana is as effective as Zolpidem (Ambien) as a sleep aid, but without the lethargy and mental fog the next morning.
- jdietrich 1y ago
  >the war on drugs has effectively eliminated the ability for legitimate researchers to do significant research on these criminalized drugs That's not true any more. We have a substantial body of data already from clinical trials and a huge number of trials currently in the pipeline. The results from completed trials are quite equivocal - while psilocybin does appear to work as a treatment for depression, anxiety and other common psychological disorders, we have no evidence yet to suggest that it is meaningfully more effective than current treatments. We have good reason to believe that psychedelics may be useful for some patients in some circumstances, but the widespread talk of a revolution in psychiatry is pure hype. https://pubmed.ncbi.nlm.nih.gov/?term=psilocybin&filter=pubt.clinicaltrial https://pubmed.ncbi.nlm.nih.gov/?term=psilocybin&filter=pubt... https://clinicaltrials.gov/search?intr=psilocybin&aggFilters=status:not%20rec%20act%20com https://clinicaltrials.gov/search?intr=psilocybin&aggFilters...
emtel 1y ago
I'm not saying you're wrong on the limitations of these studies, but I also don't think it's unreasonable for people to believe in the power of these drugs. For many people (myself included) taking psychedelics was an immediately life altering experience. I don't need any more scientific validation that psychedelics helped me than I would need to prove that touching a hot stove burned me. It's an immediate and unmistakable effect that is wholly different from any other experience I've had. Now, proving that these drugs would be beneficial at a population level may be an unanswered scientific question. But, to quote you: "trying to prove psilocybin works for psychiatric illness" - well, that's been done. The people who have been helped have all the proof they need. I think the issues you've raised are more properly targeted at the question "should we recommend psilocybin treatment to depression patients more broadly" which is in fact a much higher bar than "do they work?"
- jtrn 1y ago
  I can respect this view 100%. And your rephrasing, "Should we recommend psilocybin treatment to depression patients more broadly," is in perfect sync with my thinking, and the right question to ask. I would only add that it's extremely hard to know if something actually works. There are seriously some medications that people claim don't work, but objectively they are healthier, happier, more social, more active, and "better" on almost every objective measure. An example of this is when you really have a good match with venlafaxine for co-morbid panic disorder and depression. Then there are drugs everybody claims are good for them, but they almost never are, especially in the long run. Basically, all of the benzo sleeping aids (in the context of chronic use). So I can't and won't say you are not right. But I hope you permit me my goal of finding "objective" markers for saying "something works." Because, to quote Murderbot, "Humans are idiots!" (me included). And self-report is a notoriously unreliable measure.
  - emtel 1y ago
    > But I hope you permit me my goal of finding "objective" markers for saying "something works." A very worthy goal!

by jtrn 1y ago

motoboi 1y ago

To better appreciate his point, read “The Control Group Is Out Of Control”: https://slatestarcodex.com/2014/04/28/the-control-group-is-out-of-control/ https://slatestarcodex.com/2014/04/28/the-control-group-is-o...

johndhi 1y ago

Why do you say the effect sizes are inflated?

jtrn 1y ago
Due to a small, self-selected sample, biased toward educated, prior hallucinogen users, inadequate blinding, p-hacking via uncorrected multiple tests on 17+ outcomes, and crossover design flaws that confound long-term effects with intensive therapy. Similar psychedelic therapy claims—for LSD/psilocybin alleviating cancer-related anxiety/depression—have echoed since the 1950s-1970s, yet they've never panned out into practical, scalable clinical therapies. This alone should raise a MASSIVE Bayesian statistics red flag, due to prior discount: with decades of unfulfilled hype. At this point new evidence requires extraordinary proof to update our view. If such massive effectiveness were true, it would blow what we already have out of the water, and I would be the first to promote it to my patients. But you know what they say when something sounds too good to be true.

pas 1y ago

FDA approved in 2018 for (treatment-resistant) depression? https://www.prnewswire.com/news-releases/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression-834088100.html https://www.prnewswire.com/news-releases/compass-pathways-re... ?

jtrn 1y ago
https://www.fda.gov/drugs/resources-information-approved-drugs/olaratumab-lartruvo https://www.fda.gov/drugs/resources-information-approved-dru... !
Aurornis 1y ago
That’s not what that means. Breakthrough Therapy designation means they can continue to study it with support. It does not mean it’s approved for depression.

cmrdporcupine 1y ago

Thank you for this. I am neither an advocate nor against psychedelic use in therapy but as a person who has consumed these things in the past, my own experiences make me entirely skeptical of people who put on an advocacy hat around any particular chemical. Especially psychedelics like psilocybin which are extremely unpredictable. When I was a teen a friend gave me an analogy that stuck with me. In much older computers (e.g. C64, Vic-20, etc), they'd behave "interestingly" when you mucked around with the physical circuit board or there was a fault. E.g. if something short circuited because a screw was loose in the board, or a cartridge was halfway in or a chip partially desocketed, etc. Characters would appear in random places, or the machine go through odd loops and so on. And to someone who didn't know how the machine worked, there could be a certain "magic" and a "pattern" to this. But clearly you'd be missing the point if you thought you had "enhanced" the machine this way. LSD and psilocybin are kind of like that, but for your brain. They short circuit and alter pathways. In ways that can be entertaining but you're entirely missing the point if you try to assign a higher meaning to them. Our brains are expert pattern-finding machines, and produce causes and reasons even when there are none. For some there may be value in the experience of altering the operation of your brain to get yourself out of a stuck pattern, I guess. But I am not sure the very random stochastic nature of the whole thing is ... medicinal.

landl0rd 1y ago

Most people involved in it are aware at some level that this is at best suspect and at worst a deception designed to push legalization. Same as the “health benefits of marijuana” crowd who violently deny the risks, addictive nature, potential to induce schizophrenia (temporary or permanent), tendency to make people lazy and obese, etc. Legalization has never been a question of “is this good for people?”

jtrn 1y ago
Plot twist, I'm for full legalization.
- landl0rd 1y ago
  So am I, of both "hard" and "soft" drugs. I'm just pointing out the ridiculous approach some people choose to take rather than arguing from principled grounds. It's also a dangerous one: "we shouldn't use state violence against people who use X" is a moral position. "I'm going to spread lies that may lead more people to use dangerous substance X because I want to get high" is a very immoral one.
  - jtrn 1y ago
    I think I agree. But I come at it from a different angle. I only care if proposed therapies actually work, when people claim they do. I think the state has a horrendous track record of deciding what people are allowed to do with their own life. And I think drug enforcements are a waste of resources. I think almost all drugs are terrible and should never be taken. To me, all of these are simultaneously true.
    - tavavex 1y ago
      Out of curiosity, which drugs do you consider to be the exception to the "almost all drugs are terrible" line?
      - jtrn 1y ago

throwaway330935 1y ago

>Welcome to year 30 of trying to prove psilocybin works for psychiatric illness. That is true, but it misses some important nuance: the war on drugs has effectively eliminated the ability for legitimate researchers to do significant research on these criminalized drugs. For example, for me personally, a mild dose of marijuana is as effective as Zolpidem (Ambien) as a sleep aid, but without the lethargy and mental fog the next morning.

jdietrich 1y ago
>the war on drugs has effectively eliminated the ability for legitimate researchers to do significant research on these criminalized drugs That's not true any more. We have a substantial body of data already from clinical trials and a huge number of trials currently in the pipeline. The results from completed trials are quite equivocal - while psilocybin does appear to work as a treatment for depression, anxiety and other common psychological disorders, we have no evidence yet to suggest that it is meaningfully more effective than current treatments. We have good reason to believe that psychedelics may be useful for some patients in some circumstances, but the widespread talk of a revolution in psychiatry is pure hype. https://pubmed.ncbi.nlm.nih.gov/?term=psilocybin&filter=pubt.clinicaltrial https://pubmed.ncbi.nlm.nih.gov/?term=psilocybin&filter=pubt... https://clinicaltrials.gov/search?intr=psilocybin&aggFilters=status:not%20rec%20act%20com https://clinicaltrials.gov/search?intr=psilocybin&aggFilters...

emtel 1y ago

I'm not saying you're wrong on the limitations of these studies, but I also don't think it's unreasonable for people to believe in the power of these drugs. For many people (myself included) taking psychedelics was an immediately life altering experience. I don't need any more scientific validation that psychedelics helped me than I would need to prove that touching a hot stove burned me. It's an immediate and unmistakable effect that is wholly different from any other experience I've had. Now, proving that these drugs would be beneficial at a population level may be an unanswered scientific question. But, to quote you: "trying to prove psilocybin works for psychiatric illness" - well, that's been done. The people who have been helped have all the proof they need. I think the issues you've raised are more properly targeted at the question "should we recommend psilocybin treatment to depression patients more broadly" which is in fact a much higher bar than "do they work?"

jtrn 1y ago
I can respect this view 100%. And your rephrasing, "Should we recommend psilocybin treatment to depression patients more broadly," is in perfect sync with my thinking, and the right question to ask. I would only add that it's extremely hard to know if something actually works. There are seriously some medications that people claim don't work, but objectively they are healthier, happier, more social, more active, and "better" on almost every objective measure. An example of this is when you really have a good match with venlafaxine for co-morbid panic disorder and depression. Then there are drugs everybody claims are good for them, but they almost never are, especially in the long run. Basically, all of the benzo sleeping aids (in the context of chronic use). So I can't and won't say you are not right. But I hope you permit me my goal of finding "objective" markers for saying "something works." Because, to quote Murderbot, "Humans are idiots!" (me included). And self-report is a notoriously unreliable measure.
- emtel 1y ago
  > But I hope you permit me my goal of finding "objective" markers for saying "something works." A very worthy goal!