Comment by photochemsyn | Hacker News Reader

Comment by photochemsyn | Hacker News Reader

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Probably the key line in the abstract is:

> "Our results indicate health and wellness motives and perceived mental health benefits among microdosers, and highlight the need for further research into the mental health consequences of microdosing including studies with rigorous longitudinal designs."

It's not an unusual approach: 'We have some preliminary indications that X results in Y, but to confirm or reject this hypothesis we'll need more rigorous studies.'

It's basically going to be the centerpiece of a grant proposal to do that work.

What would be really interesting is to set up a double-blind placebo study comparing the results of using antidepressants (SSRIs etc.) with the results of using psilocybin at similar levels.

It would also be interesting to compare the results of a 'normal' psychedelic dose (full effect) taken once a month vs. the effects of daily microdosing or daily antidepressant use, again with a double-blind + placebo approach.

Yes! Everyone is trying to reduce risk, and once way scientists[0] reduce risk is to get preliminary results like this before spending a ton of money on a huge study. Absolutely not the final word, it's good to keep in mind the limitations when discussing it.

[0] Translate "scientists" into "the current scientific system between academic researchers and grant agencies"

> What would be really interesting is to set up a double-blind placebo study comparing the results of using antidepressants (SSRIs etc.) with the results of using psilocybin at similar levels.

https://www.nejm.org/doi/full/10.1056/NEJMoa2032994

Can you really be "blind" to taking psychedelics?

Are these doses small enough that you don't notice the immediate effects?

At the microdose level the obvious hallucinatory effects of psychedelics are not present, so I'd imagine those without prior experience with psychedelics wouldn't immediately realize they had taken an SSRI or a psychedelic.

The above comment study is pretty interesting, points to equivalent effectiveness.

Yeah, it was interesting that they phrased the conclusion negatively:

> On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants.

For no significant difference in outcome, I'd much rather have two psilocybin sessions versus daily SSRI use.

Placebo can be incredibly strong when taking low dose psychedelics, especially for inexperienced users. You begin to focus on normal parts of reality as if they aren't part of your usual experience.

If it's correctly microdosed the acutely noticed affects should be very close to placebo.

For lsd this is generally under 15~20ug, though 5ug/10ug is generally what people dose at.

These dosages aren't well established with "proper studies" but I can say that people documenting there experiences seem to establish this pretty well. The psychonauts wiki is a good place for this type of information

>two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart

I don't know how this compares to similar studies (if there are any similar studies) but microdosing is almost never done 3 weeks apart. That's usually the time frame done for macro dosing (but with multiple grams not mg).

Even the study at the top mentions that

>Reported microdoses identifed in observational research typically range from 5 to 20 μg of LSD and from 0.1 to 0.3 g of dried psilocybin mushrooms. Microdoses are most commonly used several times a week with various patterns of alternating days.

Can anyone explain to me why a journal like Nature would accept such a half-assed paper with weak conclusions that is transparently serving as a grant proposal for the experiment that would actually be interesting?

This is not Nature per se but a third tier Nature series journal.

This paper was published in Scientific Reports.

This is a lower tier Nature series journal where

Nature = flagship;

Nature XXXX (where XXXX is Neuroscience, Genetics, Methods, Metabolism…) makes up specialized second tier;

Nature Communications is a second or third tier non-specialized series journal (but still high impact)

Scientific Reports is nominal third or fourth tier.

But take this with a large dose of skepticism. The text, code, data, and metadata, are the true metrics if quality and generality of results.

And from my own work: if a study involves rodent models check if the authors studied just one type of mouse or rat. If so then consider most biological claims as provisional n=1 efforts. Unfortunately the reductionist mindset has won the day and last five decades. This is almost always true in neuroscience and genomics, fields in which well over 90% of science relies on the C57BL/6 mouse or the SD rat. As a result, claims may be exceedingly fragile—like doing all human studies with a single clone of one specific human.

Yes, it is nuts.

Rwilliams@uthsc.edu

Where can I find more info on experimental issues with mice or rats? Like the ones you mention but also how cages are positioned and so on? Aas that seems to have been a factor in other studies.

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