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Comment by j_m_b | Hacker News Reader

I'm sort of surprised they didn't extract/synthesize psilocybin directly and administer that. Decades ago, I grew a few batches of P. Cubensis. Even amongst mushrooms from the same rice cake, the dosage wildly varies. You could have a "trip" from a tiny mushroom or eat a handful of duds.

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It might be so that researchers investigate the common practice of "microdosing" and its effects, not necessarily (just) the effects of psilocybin low dosage. So they tried to closely emulate this practice, as it is done by users in real-life.

But this of course introduces more uncertainty, as you pointed out, so to have any conclusive results a much larger sample group would be needed, I think.

Also I agree with others that comparison with the baseline for each test subject, not just between the test group and control group, would be important.

I figured it was this as well - the motivation for performing the study is the anecdata from self-reports on microdosing with traditional techniques. I suspect that, if they had seen strong evidence for microdosing here - they would have moved on to investigating the effect in detail.

It would be nice if they were to study the effects of different doses of psilocybin directly. Could feed into possible depression treatments in the future... if somebody is trying to treat depression with psilocybin, they probably want a predictable dose that you can't really get eating mushrooms directly.

They just need a large batch of mushrooms and grind it to a powder and weighed out and placed in a pill capsule, much like what I saw back in high school being sold. No taste as it is in a pill capsule and the dose is pretty consistent.

Is psyocybin the only active chemical in mushrooms or is it like Marijuana where other chemicals in it can have some effect too

Psilocin is also present.

Psilocybin is not active, but is converted to active psilocin by dephosphorylation when it is digested. Mushrooms also contain some psilocin. There is active research into the effect of other tryptamines in mushrooms, including, baeocystin, norbaeocystin, and norpsilocin, and others.

(note - "in mice")

https://pubmed.ncbi.nlm.nih.gov/32077284/

One improvement is to take the entire batch and blend it up, so that at least doses from that batch are consistent. Still doesn't help inter-batch consistency for scientific studies, of course.

Same. Most psilocybin research I am familiar with synthesizes psilocybin, in part to be able to exactly control dosage, indeed. But it may also be to avoid dealing with illegal market?

I think this research was not done in the US but in another country (not sure which one?), not sure if research norms or availability or what differ there.

It's interesting that when it comes to cannabis they often do the opposite - that is they give subjects synthetic THC rather than the whole spectrum extract. THC isolate is quite nasty - but the same amount of THC combined with CBD and other cannabinoids can work wonders.

I think there may be that if they isolated psilocybin, they could have missed other compounds that play a part in causing desired effects. Obviously this is a different substance than cannabinoids, but I think when it comes to plants it makes more sense to test it exactly how subjects use it rather than use synthetics.

edit: I hope I didn't cause offence to any mushroom - of course they are not plants, but I hope you get my point.

Apparently, one of the companies actively pursing psilocybin for medicinal purposes has just patented one of the main methods of synthesis. From what I remember from the article that hit HN just last week regarding one of the main chemists for this company, this may be putting off researchers and others from using anything other than the natural mushrooms in their trials, tests, products, etc.

* https://www.vice.com/en/article/93a5x3/judges-deny-challenge...

> Even amongst mushrooms from the same rice cake, the dosage wildly varies

This is the main reason with psychoactive mushrooms overall. You can't dose exact via bio material so overdosing happens regular and could be actually harmful.

Extracting from shrooms with ethanol is quite consistent, the psilocybin isn't very soluble so after a few days soaking you can be pretty confident that the ethanol has taken up all it can. for microdosing the ethanol probably isn't enough to worry about trying to take it back out of solution, drink .25 oz or so.

Would you mind citing a case of harm caused by pharmacological effects of mushroom overdose? My own online research since your post found no such recorded instances, but perhaps we're using different terminology.

I actually cant, my knowledge is anecdotal. When I search around the web, there are articels that stating the same. Here is a (old) reddit thread:

https://www.reddit.com/r/IAmA/comments/allg3/i_used_lsd_and_... (I see this is anecdotal as well)

Its hard to find serious papers about it because most of the time its due to "abuse" of drugs and (!) mixed consums.

Anyways, I had a friend who was really into mushrooms overall (not only psychoactive ones) and while he was pretty open to drug using he stated multiple times that overdosing can lead to bad trips and so called "hängenbleiben" (I dont now the english term, it means the trip never really stops).

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