[htag]

> Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking.

Can we please stop pretending that double-blind is remotely an option for psychedelic research. The purpose of subject blinding is that the subject will not know if they received the treatment so that both groups have equal placebo effect. Psilocybin is active in such a way that it is obvious to the subject if they received placebo or the treatment.

I'd really like to see a psilocybin study where they give one group psilocybin, give another group an active placebo, and ask them if they think they are in the psilocybin group or active placebo group. I imagine people guess correctly >90% of the time.

It's possible to do good medical science without double-blind. Pretending that you are doing double-blind when you actually are not just generates doubts in the methodology.

[pmoriarty]

I've seen a talk by an MDMA researcher, who reported that there were people in her studies that swore they'd taken MDMA, had tear-filled therapeutic breakthroughs, only to later find out they'd only taken the placebo.

The mind is powerful.

[jona-f]

Interesting, I consider those kinds of delusions a bug not a feature. So my takeaway would be more "People are weird".

[dpflan]

Isn’t a requirement to have not taken the substance prior to the experiment? Hence placebo effect is possible.

[refibrillator]

I've noticed the skeptics here like to raise this argument on every article related to psychedelic research. As if they've found a gaping hole that somehow casts "doubts" on the methodology of decades worth of clinical trials.

Unfortunately this line of thinking doesn't hold up to scrutiny, and completely misses the forest for the trees. Mainly because the only implied alternative is to not blind subjects at all! How exactly would that reduce bias or otherwise improve the clinical trial design...?

> I imagine people guess correctly >90% of the time.

Yes in some cases you're right. Here's a paper from last year that does exactly what you asked [0]. They note that "Placebo could be distinguished well from active substance and correctly identified in 96% of the sessions." The placebos were ethanol and mannitol, for LSD and Psilocybin respectively.

The important takeaway is that subjects still had to guess. They didn't know their group assignment with certainty. And that is key to reducing bias.

I'd really like to see someone articulate a coherent alternative to subject blinding in psychedelic research.

[0] https://www.nature.com/articles/s41386-022-01297-2

[htag]

Yours is my favorite comment, and this type of thinking is why I bother to raise this question from time to time. I don't think this invalidates the entire line of research, but I do think it's less than fully transparent to present psychedelic research as if it were double-blind. I imagine the guess rate for a drug like atorvastatin (Liptor) is much closer to 50%. This false double-blind isn't unique to psychedelic research either. I think it's a wider fault of medical science to treat double-blind as a ritualistic silver bullet that controls for placebo instead of considering if it's applicable to all experiment designs.

Here are two ideas that I think are better than subject blinding for psychedelic research. I think the first one is the preferred method, but I think the second option is still better than using a placebo group or active placebo group.

* Have one group receive an established treatment and another group receive the psychedelic treatment. For psychedelic assisted therapy the comparison could be traditional therapies. I'm sure there are methods in the literature that promote increased creativity in subjects that could be used for this study.

* Double the treatment group. If you don't need to divide the subjects into multiple groups then you can put more subjects into the treatment group.

[recroad]

This is not necessarily true. A .17 mg dose does not make anything “obvious”. Source: experienced user here.

[kaoD]

0.17mg/kg so 13.6mg for an 80kg individual. According to Wikipedia, there are 15(±5)mg of psilocybin per gram of dried shrooms.

So yeah that's a light dose but definitely noticeable.

[ramraj07]

I don’t see how double blind is impossible here. Perhaps another drug that also gives you a high, on a base that has never taken any recreational drugs, could be viable?

[elevaet]

But that wouldnt be a great control since we'd be comparing the effects of psilocybin to that other drug instead of some kind of baseline.

[111111IIIIIII]

It would not be a control at all

[uxp100]

Wouldn’t it be an active control, which I believe is common in pharmaceutical research?

[abyssin]

Some studies use niacin for its sensation of flush.

[heavyset_go]

The active can have positive, negative or synergistic effects on cognition or whatever you're testing, as well as effects on the body and metabolism.

[state_less]

I’m curious how the medical community measures other interventions with a similar issue (e.g. talk therapy, physical therapy, surgery, etc…). How do they show efficacy when it’s obvious the person is knowingly receiving treatment >90% of the time.

If there is an acceptable measure, why are psychedelics held to a different standard?

[mhb]

Dose/response is a possible alternative.

[kodah]

> Psilocybin is active in such a way that it is obvious to the subject if they received placebo or the treatment.

Not really true. "Medicinal doses" are typically a gram or less, unless a heroic dose (>3g) is somehow medicinal now. Under a gram the effects are pretty subtle with strains like Golden Teachers. If they're using Albino Penis Envy's then the effects could be a bit more pronounced, but really only to a regular psilocybin user. You could easily induce the yawning and giggliness via other drugs.

[SanderNL]

The dose is really low. I wonder if you actually feel much.

[isoprophlex]

What?! That's about 12 mg for me; anywhere between 0.5 and 2 gr dried shroom mass. You can definitely tell that you've been dosed at that level.