3 ms·

Yes, fascinating to watch, but as usual the hype outpaces the science. Two major issues not discussed in the article: 1. How do you do a placebo-controlled tria

Yes, fascinating to watch, but as usual the hype outpaces the science. Two major issues not discussed in the article: 1. How do you do a placebo-controlled trial? All subjects will know the difference between psilocybin and placebo. And there are often huge placebo effects in depression trials. 2. No one has done a controlled trial with more than one dose. The best RCT so far, done by Compass, only followed patients up for 12 weeks. By that time there was still a numerical difference between drug and placebo, but it was narrowing and no longer significant. Extrapolating from the available data, the drug and placebo groups would have converged after 6 months. So what does that look like for a treatment? Do you have people trip every 3-6 months? How do you structure a Phase 3 trial to test the efficacy of, say, the 4th dose?

username923409 5y ago
About 1.: It's actually not so easy to assume that hallucinogen-naive test subjects will know the difference between psilocybin and placebo. Knowing the effects of a hallucinogen (i.e. reading about them) and actually experiencing the effects are quite different. At least, this is something I found surprising after experiencing a hallucinogen (or any psychoactive drug besides caffeine) for the first time.
- robbedpeter 5y ago
  For me, the experience gave me the realization that everything is a hallucination, that all of your every day experience and thoughts are constructs, and that knowledge becomes as fundamental and intimate as the sensation of breathing or touching. If you're paying attention on psychedelics, you realize that your skull is your very own Plato's cave. Going from caffeine and occasional marijuana to mushrooms was wild. You'd have a better chance of learning how to fly a helicopter from a book than understanding what psychedelics will feel like by reading or listening. Naive users might get fooled by a niacin flush or placebo, but once you've experienced it (and paid attention) there's no way you'll mistake the real thing. It also gives you the perspective needed to appreciate music like Shpongle and hippie intellectuals like McKenna and Watts. If you haven't experienced psychedelics, you're like a blind person being told about colors. You literally can't understand it until you live through it. Like orgasms or childbirth or religious ecstasy, some things transcend mere explanation. Psychedelics are great since they give you a shortcut right into the matrix, and you're confronted with the fact that you are indeed in a simulation, and that your existence in relation to the rest of the universe isn't nearly as distinct and cleanly delineated as you thought. The radical changes in personality stem from whatever neural machinery that governs openness to experience. I think it makes sense that the change makes people less depressed and anxious. You allow yourself to pay attention to other things, and it becomes easier to avoid fixating and catastrophizing everything wrong in your life.
- ProjectArcturis 5y ago
  True, the psilocybin effects might be different than expected, but I think absolutely everyone could tell the difference between psilocybin and a sugar pill.
dTal 5y ago
>How do you do a placebo-controlled trial? I'd like to see a trial in which the participants are unconscious for the duration of the "trip". This would not only be trivially blinded, but also help to establish whether the antidepressant effect stems entirely from the subjective experience, or whether there's a chemical component as well. People always say, "the trip is integral!". But we don't actually know that, do we?

username923409 5y ago

About 1.: It's actually not so easy to assume that hallucinogen-naive test subjects will know the difference between psilocybin and placebo. Knowing the effects of a hallucinogen (i.e. reading about them) and actually experiencing the effects are quite different. At least, this is something I found surprising after experiencing a hallucinogen (or any psychoactive drug besides caffeine) for the first time.

robbedpeter 5y ago
For me, the experience gave me the realization that everything is a hallucination, that all of your every day experience and thoughts are constructs, and that knowledge becomes as fundamental and intimate as the sensation of breathing or touching. If you're paying attention on psychedelics, you realize that your skull is your very own Plato's cave. Going from caffeine and occasional marijuana to mushrooms was wild. You'd have a better chance of learning how to fly a helicopter from a book than understanding what psychedelics will feel like by reading or listening. Naive users might get fooled by a niacin flush or placebo, but once you've experienced it (and paid attention) there's no way you'll mistake the real thing. It also gives you the perspective needed to appreciate music like Shpongle and hippie intellectuals like McKenna and Watts. If you haven't experienced psychedelics, you're like a blind person being told about colors. You literally can't understand it until you live through it. Like orgasms or childbirth or religious ecstasy, some things transcend mere explanation. Psychedelics are great since they give you a shortcut right into the matrix, and you're confronted with the fact that you are indeed in a simulation, and that your existence in relation to the rest of the universe isn't nearly as distinct and cleanly delineated as you thought. The radical changes in personality stem from whatever neural machinery that governs openness to experience. I think it makes sense that the change makes people less depressed and anxious. You allow yourself to pay attention to other things, and it becomes easier to avoid fixating and catastrophizing everything wrong in your life.
ProjectArcturis 5y ago
True, the psilocybin effects might be different than expected, but I think absolutely everyone could tell the difference between psilocybin and a sugar pill.

dTal 5y ago

>How do you do a placebo-controlled trial? I'd like to see a trial in which the participants are unconscious for the duration of the "trip". This would not only be trivially blinded, but also help to establish whether the antidepressant effect stems entirely from the subjective experience, or whether there's a chemical component as well. People always say, "the trip is integral!". But we don't actually know that, do we?