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Comment by tux3 | Hacker News Reader

The study design does try to mitigate blinding issues and expectancy effects, but with half of the participants reporting past use of hallucinogens, this is not going to be very effective blinding.

A majority of your low dose 1st group likely very much realizes that they're on the inactive dose.

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There's an argument to be made that traditional blinding and placebo techniques are not really relevant for interventions targeting mood or personality. e.g. anything that makes you feel better is an effective mood intervention, by definition. "blinding" in these studies is really just going through the motions to make certain authorities happy.

I would be more interested in polling the close friends and family of study participants and asking them about perceived changes. Instruct participants not to tell anyone about their experience in the study (whether they think they got a drug or how much).

It looks like the study tried to do something like this with "session monitors" who interviewed the participants the day after. They call it double-blind, but it's more like single-blind because the 3rd person assessment is the outcome measure.

The issue with relying on placebo effects is not that they aren't real/don't work (everything you said also applies to e.g. a painkiller), but that they are very context-sensitive. Deploy that drug to an individual or population with a different belief framework or contextual information about the therapy or their condition, and you won't get the desired results.

The design you mention is really interesting! Have you seen this done anywhere?

Is it even possible to solve the issue of there being no convincing placebo? Would a different hallucinogen like 4-HO-MET work, where the visual experience component is similar, but the visceral effect on consciousness and thought patterns is less pronounced, almost sober like?

"Well everything looks exactly the same to me, and the guy over there is staring at the carpet and whispering about The Fractals, so I think I'm in the control group"

Of course things get really complicated when this guy is messing with your control group https://xkcd.com/790/

Or they could give them a different psychedelic to test the efficacy of psilocybin specifically would be my thought.

Seems that most hallucinogens have similar benefits, with “more powerful” drugs having a more profound effect. Here’s a study on social learning in mice [1]. TLDR: length of trip correlates strongly to duration of treatment effect (eg 6 hour trip -> 1 week effect, 36 hour trip -> 6+ month effect IIRC).

Psylocybin isn’t the most studied because it’s likely to be the most effective drug. It’s because the therapists/grad students can work an 8 hour day instead of providing 12+ hour care for LSD or multi-day treatment with Ibogaine.

[1]: https://www.nature.com/articles/s41586-023-06204-3

I think this says more about the usual psy drugs we're prescribed and use.

they don't do jack shit.

Mine have definitely helped me, as if I miss them for a day I get noticeably worse

Those can be "discontinuation effects" rather than lack of treatment. I'm not saying they aren't doing good for you, but it's important to bear in mind that acute symptoms from missing a dose can be a different thing.

Sorry, but I'd be dead without mine. I'm going to have to disagree with you.

The interesting thing with mushrooms is that you could eat a handful, realize you are already dead, and then maybe not need the other meds at all.

This could be interpreted as psychedelic ego death from psilocin, backdooring into some kind of personal revelation.

Or as clinical death from Amanita toxicity, with some meta commentary on religion.

+1. :)

The very apparent effect these things have makes you wonder if they do not (somehow) correct for what otherwise could be a built-in deficiency we carry with us, by "design" correcting some sort of built-in imbalance ...

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