The recent #psilocybin vs. alcoholism trial used an active placebo (diphenhydramine). Despite this ~94% correctly guessed their treatment, showing that blinding didn't work. IMO this shows that active placebos likely wont solve the blinding issue of #psychedelic trials, a 🧵
Active placebos may have perceivable effects, but these wont confuse most patients, because psychedelics have very specific subjective effects. When a patient experiences drug effects, in most cases its easy to decipher whether its due to a psychedelic or some other drug.
Even if someone is unfamiliar with psychedelic effects going into a trial, modern ethical research standards require doctors to discuss likely effects with patients, making blind breaking that much easier
Theoretically, a true active placebo would need to: contain all non-therapeutic features of the test treatment (1) and have no additional features other than the non-therapeutic features of the test treatment (2).
I am not aware of any substance that could even approximately satisfy these conditions when psychedelics are the test treatment. Active placebos are cool as a concept, but in practice finding the right substance is very challenging.
These issues are related to questions about the role of subjective experience in psychedelic's therapeutic potential. Lots of cool upcoming work in this area!
In summary, the field should keep experimenting with active placebos, but based on what we know today, it seems to me that active placebos are unlikely to solve psychedelic trials' blinding issue.
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