[Aurornis]

Psilocybin is harder to get research approvals for than many things, but it’s not “completely banned”. There are studies every year being completed with psilocybin, many of which get posted here on HN.

There is a growing tension between the extraordinary pop culture claims of psilocybin curing everything (now extending to Alzheimer’s due to this 1 low-quality report from Brazil) and the actual studied effects, though. A lot of the published outcomes are surprisingly low quality, like this case report or all of the studies that neglect to include a control group. Mental health studies without a control group are basically useless because even a control group that doesn’t receive a placebo (that is, people you simply monitor and interact with) will get better.

Just look at this comment section: People raising suspicions about the obvious problems in the study are being downvoted. The top voted comments are citing a Joe Rogan podcast with a guy hyping his startup. People really, really want to believe this is a magic cure and the usual guardrails of suspicion for extraordinary claims are seemingly suspended for this one topic.

[wouldbecouldbe]

When you take it, you understand, that if taken with the right approach it can lead to profound insights in changing your life and the effects described: helping with depression, addiction and accepting death are not far fetched at all. Yet it can also, if not guided or done on someone with anxiety have the opposite effect.

The more biological effects I agreed are not conclusion that can be drawn from that.

[D-Machine]

Right, when you take it, it becomes clear it just injects salience / profundity / meaning into whatever you happen to be focused on or have on your mind (EDIT: mostly this is the main effect, but there can be novel perspectives / insights, and other audio-visual changes, but IMO it is the felt meaning that primarily drives the more credulous claims). Without adequate preparation, this is likely to be worthless in most cases, harmful in other cases, and helpful in some again. However, not all causes of depression or addiction are about accepting death, or a salience / meaning problem, and even when that kind of issue is involved, a momentary experience of profound meaning is NOT actually necessarily transformative either (i.e. you can and in fact must still choose how to interpret that experience, once out of it).

So it would actually be very surprising if it was just a clear net positive overall

[helterskelter]

> However, not all causes of depression or addiction are about accepting death, or a salience / meaning problem, and even when that kind of issue is involved, a momentary experience of profound meaning is NOT actually necessarily transformative either (i.e. you can and in fact must still choose how to interpret that experience, once out of it).

I don't think it's (just) encountering the profound that ends addiction, I think it really just alters or "resets" your brain structure. I know somebody who had bit their nails for their entire life well into their 30's and after a mega dose of mushrooms they just stopped. It wasn't a shift in perspective, they just didn't have that habit anymore, or even the thought of it. They didn't even notice they stopped biting their nails until they had trouble typing.

It also seems to alleviate nerve pain, and apparently enabled one man paralyzed below the waist to walk again. Something really fundamental is getting altered.

Relevant:

https://www.theguardian.com/science/2026/may/05/magic-mushro...

Also

https://www.outsideonline.com/outdoor-adventure/exploration-...

[D-Machine]

Oh, I don't doubt that sometimes something fundamental can be altered. The best sort of broad explanation I've seen that jives with the experience is maybe the one I've found here: https://www.frontiersin.org/journals/human-neuroscience/arti..., which I think would agree with your notion of a "reset" to fundamental neural structures. And yes, for certain conditions, like cluster headaches, as far as I know, psychedelics are the only things showing much real promise.

It can also just be easy for some proponents to forget that tonnes of people do and have done these things, with no clear significant lasting effects. And it is also common even for enthusiasts to say they they need to do take trips somewhat regularly (e.g. every few weeks or months) to regain the benefits. One-off miracles obviously happen, but I think are statistically likely the exception. And you can reverse or reject your insights, so for sure the trip is only one piece of the puzzle.

I'd love to see more serious research on psychedelics in general, to better engineer for useful and changing experiences. As it stands, just "take the psychedelic, manage your set and setting, and you'll have a significant positive effect" is generally not very plausible nor I think actually supported empirically or even by most anecdotes.

[wouldbecouldbe]

I think its relatively easy to make it beneficial with an adult person taken in most serene settings & with good intentions. The studies they did do seem to reflect that.

I would advice against a too high of a dose first time. The 5 grams they normally give in studies seems to be on the high side for a first time.

[D-Machine]

Set and setting can help make a positive experience likely, yes, I think what proponents often miss is that for the vast majority of people, the experience will mostly just be "interesting" and "memorable", and not particularly transformative. I.e. transformative / curative effects seem to be rare, IMO for the reasons I already stated.

[ozgrakkurt]

> When you take it, you understand

To be fair, this is not how medical research is done.

[LoganDark]

It's also not the best idea to tell whatever board is reviewing your proposals, "just take psilocybin yourself and you'll understand"

[wouldbecouldbe]

You fortunately don't need medical research in learning how to live your life and experience meaning.

It's great if we have therapies that help people and get a proper scientific stamp. Yet we can also discover the benefits for ourselves before that stamp is given.

[lostmsu]

> You fortunately don't need medical research in learning how to live your life and experience meaning.

Here I'd disagree with you. I do need to know if you become happier because you become dumber due to brain damage or for some other magical reason. So far I haven't seen any evidence contrary to the dumber explanation.

[rerx]

In defense of the comment you replied to: Research into treatments with Psilocybin or LSD was in quite a hiatus for decades after the substances were banned in the 1960s or 70s.

[Aurornis]

I understand that, but a lot has changed since then and psilocybin is not the only substance that has been studied which interacts with those receptors.

Our ability to synthesize new compounds has also exploded since then. Drug companies are looking for the next blockbuster drug. They don’t need to use psilocybin. We can now use powerful computers to come up with countless variations of drugs that activate the receptors involve and study them rapidly. There are hundreds of ligands that interact with the same receptors.

[ux266478]

> There are hundreds of ligands that interact with the same receptors.

Except the ligands matter, binding site is massively important to drug design. As is the behavior of the molecule beyond that. A 5HT2A agonist that's also an irreversible and potent dopamine agonist is obviously a non-starter. Minor modifications of a molecule produce wildly different and very unpredictable effects. Pharmacodynamics and pharmacokinetics are the bottleneck of drug research, and they take quite a lot of work to understand.

> We can now use powerful computers to come up with countless variations of drugs that activate the receptors involve and study them rapidly.

"Research chemical" is common parlance, and it's synonymous with "dangerous gutter drug" because you end up with nasty little molecules like what's found in the 25-NB or FLY families, or something like MDMB-CHMNACA. If it ain't broke, don't fix it. Our algorithmic and predictive power in pharmacology is one of the absolute worst out of all the sciences. The absolute state of this naive futurist mindset that we can move fast in drug research is absolutely horrifying to even suggest. That's not where the state of the art is, and I'd put big money on us not getting there for another 100k years or so.

[tim-star]

certainly you should understand the context of the comment then- the commenter was saying we had a 40 year moratorium on research because of the governments decisions at the time. There is a lot of research again now, but research takes time.

[new-treatment]

Very notably Definium Therapeutics (Formerly MindMed) has synthesized an orally disintegrating LSD pill. Given almost zero historical toxicity, I think it is mostly stuck in some societal acceptance limbo for this class of meds. Strange if one sees how openly accepted THC/etc are

[ifwinterco]

Acid is always orally active and tabs are tiny, it being hard to administer was never the issue

[hn_throwaway_99]

> A lot of the published outcomes are surprisingly low quality, like this case report or all of the studies that neglect to include a control group. Mental health studies without a control group are basically useless because even a control group that doesn’t receive a placebo (that is, people you simply monitor and interact with) will get better.

Honest question, does a control group really matter that much when it's not possible to do a blinded study? Unless it's some incredibly small microdose, I would assume most study participants are able to tell if they're tripping or not.

[NoMoreNicksLeft]

>There is a growing tension between the extraordinary pop culture claims of psilocybin curing everything (now extending to

That's the playbook that got marijuana (more or less) legalized. So of course they're going to use the same exact strategy with each drug in turn.