4 ms·

>New study finds psilocybin greatly and quickly relieves depression Nope, it doesn't. The study wasn't placebo controlled. The placebo effect will have a large

>New study finds psilocybin greatly and quickly relieves depression Nope, it doesn't. The study wasn't placebo controlled. The placebo effect will have a large effect in a study like this, so we have no idea what effect the psilocybin had.

LegitShady 6y ago
I wonder about posts with studies like these when just earlier there was one about how to read scientific papers.
modeless 6y ago
What kind of placebo could you use to stand in for a treatment that normally has immediate and obvious side effects like this one?
- hristov 6y ago
  You can just use the standard sugar pill placebo. But of course make sure the placebo group get the same treatment of lying on a couch and listening to music with their eyes closed. I am sure the psychedelic effects of shrooms would increase the placebo effect greatly, so sugar pill placebo might not correctly show the placebo effect, but it is a start.
  - ramraj07 6y ago
    How about the combination of the drug and the experience is the treatment? In that case the placebo is telling someone with depression to sign up and stay at home. Which is still important.
  - jolmg 6y ago
    > so sugar pill placebo might not correctly show the placebo effect The lack of good placebo options seems to be why they chose not to have a placebo. The paper mentions: > Although placebo and active treatment controlled designs are widely used in therapeutic trials, they too have limitations owing to the highly discriminable effects of psilocybin.
    - hristov 6y ago
      That seems a bit of copout though. Yes, sugar pill will not have a as high placebo effect but it is still useful as setting a lower bound on the placebo effect.
      - jolmg 6y ago
        Wouldn't it complicate things by introducing a new variable to consider, i.e. how gullible is each participant / how affected were they by the placebo? For what it's worth, it seems more useful to not have that variable. That way, if the effect was from the psilocybin acting as placebo, at least you know they were all affected equally. There were too few participants too. Having a control group with a placebo would make the experimental sample even smaller.
- theptip 6y ago
  Yeah this objection is a red herring. You need to look at the effect size. If you have found a protocol where (according to the study author) "the magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market", if it's just a placebo, that sounds like a great placebo to be giving! As noted above I seriously doubt the concept of a placebo is even well-formed for psychedelics. I quite like Scott Alexander's take on this issue: > Actual carefully-researched psychiatric drugs are exquisitely selected for having few side effects. The goal is something like an SSRI – mild stomach discomfort, some problems having sex, but overall you can be on them forever and barely notice their existence. In the grand scheme of things their side effects are tiny – in most placebo-controlled studies, people have a really hard time telling whether they’re in the experimental or the placebo group. > Nobody has a hard time telling whether they’re in the experimental or placebo group of a trial of high-dose MDMA. I think this might be the difference. If you go for large effects – even if you don’t really care what direction the effect is in – you’ll get them. And if you go for small, barely perceptible effects, then you’ll get those too. https://slatestarcodex.com/2017/06/05/is-pharma-research-worse-than-chance/ https://slatestarcodex.com/2017/06/05/is-pharma-research-wor... Also see https://slatestarcodex.com/2018/01/31/powerless-placebos/ https://slatestarcodex.com/2018/01/31/powerless-placebos/ > All three looked at studies comparing a real drug, a placebo drug, and no drug (by the third, over 200 such studies) – and, in general, found little benefit of the placebo drug over no drug at all. There were some possible minor placebo effects in a few isolated conditions – mostly pain – but overall H&G concluded that the placebo effect was clinically insignificant. > What happened? Probably placebo effects rode on the coattails of a more important issue, regression to the mean. That is, most sick people get better eventually. This is true both for diseases like colds that naturally go away, and for diseases like depression that come in episodes which remit for a few months or years until the next relapse.
  - cpncrunch 6y ago
    >if it's just a placebo, that sounds like a great placebo to be giving! Even for antidepressants, the placebo effect makes up 67.6% of the effectiveness [1], so the placebo is always much more effective than antidepressants. >Also see https://slatestarcodex.com/2018/01/31/powerless-placebos/ https://slatestarcodex.com/2018/01/31/powerless-placebos/ Hmmm, that seems to be a review from 2004. Newer data [2] shows that placebos can affect autonomic, neuroendocrine and immune responses and pain responses. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130402/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130402/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/
- PeterisP 6y ago
  Probably the control should be some other psychoactive substance that also has some noticeable hallucinogenic effect, but is not believed to have curative properties. The other way (which is close to what they have done) is to compare and contrast the therapeutic effects of different dosages - if the patient feels the expected sideeffects in both cases, but the normal dose achieves measurably better results than a minimally low dose, then that's some evidence about the effectiveness of the active ingredient.
  - jointpdf 6y ago
    They’ve used Ritalin as well, since it has obvious psychoactive properties and also causes some of the same physical effects as psilocybin (increase in heart rate, sweating, etc). https://www.discovermagazine.com/mind/do-magic-mushrooms-make-you-mystical https://www.discovermagazine.com/mind/do-magic-mushrooms-mak...
- PragmaticPulp 6y ago
  You don't need placebo. That's a common misconception. They could have used an active control group that received traditional antidepressants. This study wasn't actually about psilocybin, it was about psilocybin-assisted therapy. So they could have simply had one group receive only therapy and the other group receive therapy plus psilocybin.
  - cpncrunch 6y ago
    >They could have used an active control group that received traditional antidepressants. Traditional antidepressants take days or weeks to have an effect, and the effect is very different from psilocybin. >So they could have simply had one group receive only therapy and the other group receive therapy plus psilocybin. That still wouldn't tell you if the psilocybin itself had any effect over and above the placebo effect.
    - PragmaticPulp 6y ago
      > Traditional antidepressants take days or weeks to have an effect, and the effect is very different from psilocybin. Which is fine. Double-blind is great when you can pull it off, but it's fallacious to dismiss control groups just because they can't be perfectly blinded. Active control groups and non-blinded studies are still used frequently in these situations. There's no excuse for discarding control groups completely.
- cwkoss 6y ago
  One early study of psychedelics used niacin as the placebo. All the patients were in the same room (not a great study design IMO) All of the control patients experienced niacin flushing before the treatment patients started having effects, so many treatment patients initially thought they were in the control group.
- esperent 6y ago
  You couldn't use a placebo, but you could use a different psychoactive drug such as ketamine which is also being tested for use on depression.
m12k 6y ago
Yeah, I'm going to want the same psychotherapy given to a group given psilocybin, a group given traditional antidepressants, and a group given placebo (with the psychotherapist blinded to administered drug).
- gjs278 6y ago
  it will be plainly obvious who got the placebo
sjg007 6y ago
How about we read the paper first before jumping to conclusions. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2772630 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/... Findings In this randomized clinical trial of 24 participants with major depressive disorder, participants who received immediate psilocybin-assisted therapy compared with delayed treatment showed improvement in blinded clinician rater–assessed depression severity and in self-reported secondary outcomes through the 1-month follow-up. Meaning This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder.
- jolmg 6y ago
  From the guidelines: > Please don't comment on whether someone read an article. "Did you even read the article? It mentions that" can be shortened to "The article mentions that." From the paper: > Strengths and Limitations ... Further research with ... a placebo control is needed to better ascertain the ... efficacy of this intervention among patients with MDD. > Conclusions ... Further studies are needed with active treatment or placebo controls The paper explicitly mentions that there's no placebo control, so I'm not sure what you're trying to point out with your comment.
- deleted 6y ago
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LegitShady 6y ago

I wonder about posts with studies like these when just earlier there was one about how to read scientific papers.

modeless 6y ago

What kind of placebo could you use to stand in for a treatment that normally has immediate and obvious side effects like this one?

hristov 6y ago
You can just use the standard sugar pill placebo. But of course make sure the placebo group get the same treatment of lying on a couch and listening to music with their eyes closed. I am sure the psychedelic effects of shrooms would increase the placebo effect greatly, so sugar pill placebo might not correctly show the placebo effect, but it is a start.
- ramraj07 6y ago
  How about the combination of the drug and the experience is the treatment? In that case the placebo is telling someone with depression to sign up and stay at home. Which is still important.
- jolmg 6y ago
  > so sugar pill placebo might not correctly show the placebo effect The lack of good placebo options seems to be why they chose not to have a placebo. The paper mentions: > Although placebo and active treatment controlled designs are widely used in therapeutic trials, they too have limitations owing to the highly discriminable effects of psilocybin.
  - hristov 6y ago
    That seems a bit of copout though. Yes, sugar pill will not have a as high placebo effect but it is still useful as setting a lower bound on the placebo effect.
    - jolmg 6y ago
      Wouldn't it complicate things by introducing a new variable to consider, i.e. how gullible is each participant / how affected were they by the placebo? For what it's worth, it seems more useful to not have that variable. That way, if the effect was from the psilocybin acting as placebo, at least you know they were all affected equally. There were too few participants too. Having a control group with a placebo would make the experimental sample even smaller.
theptip 6y ago
Yeah this objection is a red herring. You need to look at the effect size. If you have found a protocol where (according to the study author) "the magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market", if it's just a placebo, that sounds like a great placebo to be giving! As noted above I seriously doubt the concept of a placebo is even well-formed for psychedelics. I quite like Scott Alexander's take on this issue: > Actual carefully-researched psychiatric drugs are exquisitely selected for having few side effects. The goal is something like an SSRI – mild stomach discomfort, some problems having sex, but overall you can be on them forever and barely notice their existence. In the grand scheme of things their side effects are tiny – in most placebo-controlled studies, people have a really hard time telling whether they’re in the experimental or the placebo group. > Nobody has a hard time telling whether they’re in the experimental or placebo group of a trial of high-dose MDMA. I think this might be the difference. If you go for large effects – even if you don’t really care what direction the effect is in – you’ll get them. And if you go for small, barely perceptible effects, then you’ll get those too. https://slatestarcodex.com/2017/06/05/is-pharma-research-worse-than-chance/ https://slatestarcodex.com/2017/06/05/is-pharma-research-wor... Also see https://slatestarcodex.com/2018/01/31/powerless-placebos/ https://slatestarcodex.com/2018/01/31/powerless-placebos/ > All three looked at studies comparing a real drug, a placebo drug, and no drug (by the third, over 200 such studies) – and, in general, found little benefit of the placebo drug over no drug at all. There were some possible minor placebo effects in a few isolated conditions – mostly pain – but overall H&G concluded that the placebo effect was clinically insignificant. > What happened? Probably placebo effects rode on the coattails of a more important issue, regression to the mean. That is, most sick people get better eventually. This is true both for diseases like colds that naturally go away, and for diseases like depression that come in episodes which remit for a few months or years until the next relapse.
- cpncrunch 6y ago
  >if it's just a placebo, that sounds like a great placebo to be giving! Even for antidepressants, the placebo effect makes up 67.6% of the effectiveness [1], so the placebo is always much more effective than antidepressants. >Also see https://slatestarcodex.com/2018/01/31/powerless-placebos/ https://slatestarcodex.com/2018/01/31/powerless-placebos/ Hmmm, that seems to be a review from 2004. Newer data [2] shows that placebos can affect autonomic, neuroendocrine and immune responses and pain responses. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130402/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130402/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013051/
PeterisP 6y ago
Probably the control should be some other psychoactive substance that also has some noticeable hallucinogenic effect, but is not believed to have curative properties. The other way (which is close to what they have done) is to compare and contrast the therapeutic effects of different dosages - if the patient feels the expected sideeffects in both cases, but the normal dose achieves measurably better results than a minimally low dose, then that's some evidence about the effectiveness of the active ingredient.
- jointpdf 6y ago
  They’ve used Ritalin as well, since it has obvious psychoactive properties and also causes some of the same physical effects as psilocybin (increase in heart rate, sweating, etc). https://www.discovermagazine.com/mind/do-magic-mushrooms-make-you-mystical https://www.discovermagazine.com/mind/do-magic-mushrooms-mak...
PragmaticPulp 6y ago
You don't need placebo. That's a common misconception. They could have used an active control group that received traditional antidepressants. This study wasn't actually about psilocybin, it was about psilocybin-assisted therapy. So they could have simply had one group receive only therapy and the other group receive therapy plus psilocybin.
- cpncrunch 6y ago
  >They could have used an active control group that received traditional antidepressants. Traditional antidepressants take days or weeks to have an effect, and the effect is very different from psilocybin. >So they could have simply had one group receive only therapy and the other group receive therapy plus psilocybin. That still wouldn't tell you if the psilocybin itself had any effect over and above the placebo effect.
  - PragmaticPulp 6y ago
    > Traditional antidepressants take days or weeks to have an effect, and the effect is very different from psilocybin. Which is fine. Double-blind is great when you can pull it off, but it's fallacious to dismiss control groups just because they can't be perfectly blinded. Active control groups and non-blinded studies are still used frequently in these situations. There's no excuse for discarding control groups completely.
cwkoss 6y ago
One early study of psychedelics used niacin as the placebo. All the patients were in the same room (not a great study design IMO) All of the control patients experienced niacin flushing before the treatment patients started having effects, so many treatment patients initially thought they were in the control group.
esperent 6y ago
You couldn't use a placebo, but you could use a different psychoactive drug such as ketamine which is also being tested for use on depression.

m12k 6y ago

Yeah, I'm going to want the same psychotherapy given to a group given psilocybin, a group given traditional antidepressants, and a group given placebo (with the psychotherapist blinded to administered drug).

gjs278 6y ago
it will be plainly obvious who got the placebo

sjg007 6y ago

How about we read the paper first before jumping to conclusions. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2772630 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/... Findings In this randomized clinical trial of 24 participants with major depressive disorder, participants who received immediate psilocybin-assisted therapy compared with delayed treatment showed improvement in blinded clinician rater–assessed depression severity and in self-reported secondary outcomes through the 1-month follow-up. Meaning This randomized clinical trial found that psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder.

jolmg 6y ago
From the guidelines: > Please don't comment on whether someone read an article. "Did you even read the article? It mentions that" can be shortened to "The article mentions that." From the paper: > Strengths and Limitations ... Further research with ... a placebo control is needed to better ascertain the ... efficacy of this intervention among patients with MDD. > Conclusions ... Further studies are needed with active treatment or placebo controls The paper explicitly mentions that there's no placebo control, so I'm not sure what you're trying to point out with your comment.
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