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Comment by ericmcer | Hacker News Reader

The effects of low doses of mushrooms/MDMA make me wonder if we have been going about it all wrong. You can easily take 20% of the normal amount and have a pleasant and noticeable effect but still be highly functional. It is like our "normal" dose for those drugs is the equivalent of 6+ drinks, and the idea of only having a beer or two is painted as a waste.

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It’s not the same though. A high dose can lead to life altering insights. A low dose will just be a fun time.

Alcohol in higher doses isn’t therapeutic. More than 4 beers and any therapeutic effect alchohol could’ve had is now also gone. :)

Just this weekend I took a low dose of mushrooms and went to a nightclub. I typically drink at these places so it was interesting to take just mushrooms and zero booze.

It was quite fun at a low dose and gave a similar feeling to being drunk without the downsides. After that experience if I had to choose to go out and drink or go out and take a low dose of mushrooms I'm definitely doing the latter.

Microdoses have no real effect on me at best, and put me totally on edge at worst. But I love a mild 1-2g trip. I personally think the optimal dose is a mild tripping dose (perhaps mid ~3.5g if you are experienced and are looking for that kind of experience).

But at the end of the day, everyone reacts different. I don't know if there is a point to characterizing what should be 'normal' dosage. They are basically completely different drugs with different uses at different doses.

> The effects of low doses of _______ make me wonder if we have been going about it all wrong

It's human nature to think that more is better. If a little works, why not use more. There's a definite bit of experimenting that should be done to see when more become less effective. As a user, that's just part of the journey. Then we have the marketing/sales view point where they just want those numbers higher, but it actually makes to product less but not in a way the marketing cannot overcome it. I feel this way about the microbrewery movement with high alcohol and hops=>IPA usage.

melatonin is one where 1 mg works and 10 mg doesn't.

For the psychedelics this is very true, I enjoy mostly low doses. But I am not so sure about the MDMA. If I didn't have enough to get "over the hill" it always felt it's about to come on now but it never does it's just a very dissapointing limbo state. Even worse, redosing after that won't get you the full effect either for that night (maybe because some serotonin was already depleted at that point).

The common knowledge amongst enthusiasts is that shrooms have a threshold below which you don’t feel anything and I feel like anecdotally I can vouch for that (though it’s been a long time and I can’t exactly remember anymore).

I've done it a few times. The 1.75g was one of the most profound moments of my life and the .25g were just an interesting night. Felt like a 20x difference to me.

Micro dosing psylocibe/psylocin on a regular basis puts your heart valves at some risk of permanent damage in ways occasional high dose use does not.

You got a reference to back that up?

Yes, this is the first I've heard of this but I would be interested in learning about it.

Psilocybin is a partial 5-HT2B receptor agonist. 5-HT2B receptor agonism causes deposits of collagen in heart valves (which will lead to valve disease). This is true for LSD, MDMA, and psilocybin.

A note is that psilocybin is only a partial agonist, and the dosages taken for micro-dosing may not be comparable to something like fenfluramine (a drug which does cause heart valve dysfunction for certain). There was a drug nerds thread lying around on Reddit where the theoretical receptor activations were compared. IIRC, psilocybin is not a major risk, as long as you're not tripping every day for months on end.

The risk comes from taking the 2b agonist regularly, that's why it causes fibrosis. Not only is taking the larger dose safer as long as there are no preexisting cardiovascular issues but microdosing has been shown to be no better than placebo

Microdoses also don't inspire hippocampal neurogenesis whereas larger doses do

Microdosing is not only not beneficial but it may be actively harmful

"...it is possible that chronic microdosing may carry a risk of fibrosis and VHD, which should be assessed in future studies. There is converging evidence that simulation of the 5-HT2BR over several months may lead to the development of fibrosis. Duration of intake plays a major role in drug-induced VHD, even if the substance is not taken daily (Connolly et al., 1997; Schade et al., 2007)."

https://journals.sagepub.com/doi/full/10.1177/02698811231225...

https://blog.petrieflom.law.harvard.edu/2022/04/13/safety-fi...

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