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Comment by reissbaker | Hacker News Reader

TBH there's no way to have a double blind trial of drugs like psilocybin (Scott Alexander has written a little bit about this [1] with respect to controlled trials for MDMA), for any reasonable dose size of psilocybin. Both the patient and the person administering the drug will become very aware, very quickly, if they're in the psilocybin group.

1: https://slatestarcodex.com/2017/06/05/is-pharma-research-wor...

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This is wrong. You can absolutely dose psylocybin at levels that make a meaningful difference in experience (certainly enough to have an anti-depressant effect) without “tripping” or being in any way impaired. For many adults, this will be around 100-200mg of psilocybin.

Microgram, not milligram, of psilocybin. 100mg of psilocybin would be about 50-200 grams of dried cubensis mushroom.

There have been studies on microdosing, but it’s also valuable to know what happens at perceptible doses as well. It’s certainly a different experience.

It's not a question of impairment, it's a question of whether you come to some determination of whether you are in the control group or not.

Unsurprisingly, the way around it is to introduce a third treatment or fourth, with classical psychedelic 5-HT2 action. There are a few such choices and some are also registered antidepressants, one being DXM/bupropion, another being an ergoloid derivative or a psychedelic amphetamine like DOM.

But then you need to run a trial in a hundred or two hundred N.

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