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Comment by cubefox | Hacker News Reader

Unfortunately it's hardly possible to do proper case control studies with psilocybin, since the psychedelic effects cause unblinding. The participants know whether they are in the treatment or control group.

> Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to 'let go', or breathing exercises. The important part is the integration work that comes afterwards," Barba added. [...]

> However, [Rucker] noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants

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Unfortunately it's hardly possible to do proper case control studies with psilocybin, since the psychedelic effects cause unblinding.

This is a problem with SSRIs as well; studies have found most people can correctly guess if they’re in the study group or control group.

A true double blind study would require a drug that has similar side effects via an unrelated mechanism, but nobody has attempted that as far as I’m aware.

There was this interesting one though where they deceived patients into believing they were taking an “active placebo” instead of an SSRI, and found that the benefits went away, which is very interesting and raises a lot of questions about the true efficacy of these medications: https://www.nature.com/articles/s41398-021-01682-3.pdf

If there is a medical question that double-blind studies cannot answer, that doesn't mean the question is unanswerable. It means we should be more skeptical of non-blinded studies (or worse studies that pretend to be blind), and we should look for alternative ways to address biases.

You could compare against other psychedelics. I’d be interested in that.

You could also test it on severely sleep-deprived experimenters undergoing sensory isolation, but that would never get IRB approval.

Sleep deprivation is thought to temporarily relieve depression in a lot of people, so it wouldn't really be a placebo anyway.

https://www.pennmedicine.org/news/news-releases/2017/septemb...

Yeah. Especially a comparison with LSD seems interesting. However, if both perform similarly, this could either mean they both work or they both don't work.

There are many hints at psilocybin not being different to LSD, some researchers opted for psilocybin for trials just because it was less known to the wide audience and had less cultural baggage than LSD. There are some comparisons, e.g. https://www.nature.com/articles/s41386-023-01607-2

Hardly an issue. When people do similar studies measuring say the effects of prescribed exercise vs not they are also unblinded but we still get good data.

I've never found it compelling that blinding isn't possible for drug-naive patients. There are other drugs that could induce a "trip" and an unfamiliar individual could mistake for a minor psychedelic experience.

Really? name one.

When you don't know what a psychedelic experience is, any mind altering substance could do. For someone who never got drunk, it could even include alcohol.

It is very hard to describe in words what a psychedelic experience is, so without a reference point, it is hard to tell if what you experienced is one or not.

Ok but now you're not comparing drug vs no drug but drug vs other drug. Yes it can be blind, but it's a cometely different study now

Suggestion alone can make you feel high. I remember someone telling me that he got high just by touching sweaty people in a music festival where most people were high, clearly, that's placebo. And that guy was far from drug-naive.

And they sometimes give active substances to the control arm to have an effect. I remember in a covid vaccine trial, they gave the meningitis vaccine to the control group to mimic the side effects of the covid vaccine they tried. Here, they actually gave a microdose of psilocybin (1mg) to the SSRI arm. I don't know why, but maybe it was enough for them to feel something without having the full effect.

Is alcohol the best you could do? I have a feeling that alcohol can definitely help with depression Probably one of the oldest drugs used in that regard

of course there aren’t actually that many drugs.. you clearly couldn’t give another tryptamine they are kindof all the same. I guess you could give a phenethylamine but obviously those are probably good at treating depression too so your studies gone to shit I suppose you could give a deliriant but that just sounds mean.

Dissociatives would work, like dextromethorphan or ketamine. Psychedelics are a subset of hallucinogens.

ketamine is great for depression

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