Spontaneous and deliberate creative cognition during and after psilocybin (2021) | Hacker News Reader

Spontaneous and deliberate creative cognition during and after psilocybin (2021)

nature.com

69 pointsprismatic29 comments

> 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.

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?

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.

It would not be a control at all

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

Some studies use niacin for its sensation of flush.

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.

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

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.

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?

Dose/response is a possible alternative.

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.

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

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

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

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.

> 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.

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

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.

> Conclusion In conclusion, this study found that psilocybin induces a time- and construct-related differentiation of effects on creative thinking, suggesting that psychedelics could be a novel tool to investigate underlying neural mechanisms of the creative process1,24. In addition, these findings add some support to the historical claims that psychedelics can influence aspects of the creative process, reducing conventional, logical thinking, and giving rise to novel thoughts, but emphasizes the distinction between spontaneous and deliberate creative cognition, as well as acute and persisting effects of the drug.

Anybody knows if psychedelic dosage is weight-dependent?

In research I mostly see dosages per kg, while responsible use wikis list absolute dosages (which matches my experience of user-weight not changing much of the perceived strength).

This seems natural to me since the brain does not grow with your weight and psychedelics unlike THC are not liposoluble AFAIK, but this is just me speculating and I have zero pharmaceutical-related education.

If it is weight-dependent what mechanism affects the strength?

Read what Feynman had to say about that, in "Surely you're joking, Mr. Feynman."

I read that book, but don't remember what he had to say about psilocybin. Could you provide a tl;dr? I only remember that Feynman consumed weed recreationally and liked to use it to enhance his creativity and thinking in sensory deprivation tanks, but he never tried LSD, fearing it would permanently damage his brain.

He tried LSD once, when it was still legal, at the urging of Dr. Timothy Leary. He then thought he'd solved a hard problem in physics he had been working on. While going to give a talk on the solution, he realized that he had not solved the problem, but had hallucinated that he had solved it. He was very angry. Never tried LSD again. "I like to think, and I don't want to break the machine", he wrote.

(source: https://news.ycombinator.com/item?id=27804592)

As a dabbler myself, it seems like this was The Classic™ "user error."

Imagine what Feynman could have produced if he had used LSD correctly! He could have been as productive as Jack Kerouac!

So how productive was he before and after the use of LSD?

Instead of widening the perceptual horizons as traditionally believed, psychedelics rather seem to 'switch off' certain sections of the mind - particularly the cautious area that frets over the idea of dabbling with such compounds. Those that are household names have a knack for quieting this voice of doubt first. Paradoxically, the subjective experience of liberation is born from selective self-silencing.

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