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Comment by dennnis | Hacker News Reader

"...but descriptions of other people’s hallucinogenic trips tend to be tiresome. (The son of maverick biologist Rupert Sheldrake, Merlin grew up among colourful company, and the apple clearly didn’t fall far from the tree.) He breezily describes the potential of fungal hallucinogens such as psilocybin to treat disorders like depression, downplaying the possible dangers and the mixed and still rudimentary evidence of their efficacy."

Never lists these possible "dangers" while downplaying "rudimentary" evidence...

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I think the point is that there hasn’t really been 3-phase double blinded trials to determine dosing, safety, tolerability, and efficacy as well as side effects.

Much of what we have is anecdotal.

Have you not heard of "How to change your Mind" by Michael Pollan? Or the Research of Roland Griffiths? https://scholar.google.com/scholar?hl=en&as_sdt=0%2C24&q=rol...

I am not sure your comment is accurate, the effects and benefits are definitely not anecdotal.

Re Depression treatment: https://scholar.google.com/scholar?hl=en&as_sdt=0%2C24&q=dep...

Blinded trials of active doses of a psychedelic is cargo cult science. They tried that in the Good Friday experiment: it was silly, when someone has taken a psychedelic, they know it.

That does mean there are certain assurances of neutrality we simply can't have. It doesn't mean that efficacy and safety can't be studied: they can.

No doubt - I’ve had plenty of psychedelics in my youth. However a blinded trial isn’t just about how people describe their trip. The people evaluating the results are unaware who was given placebo as well. This way they can conduct their study without bias.

Also, dosing matters. Can the apparent positive effects occur at low doses where possibly it isn’t very perceptible? This is important and a double blind approach is warranted.

Agreed that it doesn't apply to microdosing, and single-blinding the scientists handling the data is valuable.

I don't think it's as important for the attending scientists, who are also going to have a pretty accurate guess. What's more important is that they have some training in 'trip sitting' and that the experimental environment be appropriately designed, DMT: the Spirit Molecule has a number of stories about how things go poorly when this aspect is neglected.

If all participants have never tried psychedelics, maybe it could be tested against a non-psychedelic psychoactive drug so both groups would feel something?

No idea as I know relatively little about pharmacology compared to an expert. But I think you’re in the right spirit here.

The Good Friday experiment used an "active placebo" in the form of a low dose of amphetamines.

Doesn't help: any normal person can tell the difference between a full dose of psilocybin and a low dose of amphetamines.

Does the patient need to know which drug is being tested?

"You'll be given either a psychedelic or a stimulent, followed by x testing" - then knowing which drug you're getting doesn't mean you know if you're in the placebo group or not?

>I think the point is that there hasn’t really been 3-phase double blinded trials to determine [safety, tolerability]

Psilocybin is well known to be one of, if not the single safest psychoactive compound known to man, in terms of physical toxicity. Obviously, mental harm can be a possibility.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

https://www.americanscientist.org/article/the-toxicity-of-re...

I took "possible dangers" as, those that haven't been empirically ruled out. Perhaps something that affects some people, but hasn't yet been linked to psilocybin use.

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