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Comment by zug_zug | Hacker News Reader

Great point, and the study even admits that point

"Limitations: First, the success of allocation blinding was not assessed, and it is likely that the acute psychoactive effects of psilocybin produced some degree of functional unblinding that may have contributed to the observed effect in psilocybin-treated participants and the increased dropout rate in niacin-treated participants."

Unblinding = participants figure out if they got the real thing

I think a recent ketamine study found a lot of the clinical effect went away if participants weren't awake/aware of the treatment. Wonder if that could be used here.

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Yeah, though perhaps it is the trip itself that causes the antidepressive effect, so if you prevent the trip via sleep, the effect goes away.

Exactly my thought. It's often reported that the antidepressant effect came from the increased ability to look at your problems from a new perspective.

If this new perspective isn't experienced, it seems highly unlikely this would work.

Thinking about the mechanism of classic anti-depressants like SSRIs, you expect a boosted effect of the happy chemicals to make people more happy.

With anything that is few or single-dose you expect changes in thought and behavior patterns to have the antidepressant effect. These lasting changes must come from something that is not happy chemicals, but a new perspective on life.

It’s also possible that the conscious experience of the effect is part of what makes it work. I’m not sure how you would test that out.

I don’t think you can.

But if a certain action routinely produces sustained change, that can also be fine.

Eg, you can’t blind participants to whether they receive real therapy or a conversation about the weather, but we’ve concluded that therapy is useful. And you can’t for a similar reason, in that the experience is itself the treatment.

I missed that study and that is a brilliant way of blinding participants for this sort of thing.

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