> We report the case of an octogenarian Japanese-American woman with a 10-year history of Alzheimer’s disease, including 5 years of marked hypofunction and predominantly monosyllabic speech.

> The patient received 5 g of orally administered psilocybin-containing mushrooms

> Approximately 19 h post-administration, spontaneous autobiographical speech emerged. Over subsequent days and weeks, functional improvements included restoration of urinary continence, improved ambulation, autonomous dressing, increased emotional responsiveness, sustained social interaction, contextual memory retrieval, preserved working memory for social context, and spontaneous conversational engagement.

This is exactly that, a treatment using psilocybin that was successful. It's not claiming to have developed a treatment protocol, the title is precise.

So is this about temporarily overclocking some cells that would then return to a healthy baseline before collapsing back after the overclocking agent is gone? Why not just do 500mg B1 HCl IV then for a comparison to see if this was just a metabolic block?

It appears that one dose of the shrooms had positive effects observable for several weeks. That is very encouraging and hints at this being a practical treatment. (The word "transient" in the original title sets us up for disappointment, conjuring up the image of an experiment in which Alzheimer's symptoms are suspended for 20 minutes).

Questions linger about the long term use; what happens to someone who has been taking this dose, say, every two weeks for a year, or five years? Does even the second dose work as well as the first?

They do add:

> Generative AI statement

> The author(s) declared that Generative AI was not used in the creation of this manuscript.

> Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Which is good.

But it makes me wonder about “wherever possible”. In which case wouldn’t it be possible and why would it remain if it’s not possible?

edits: formatting

I would not trust predatoryjournals.org. Beside the site looking much like the worst predatory journals, they have no transparency in who they are and how they evaluate journals. It seems just to be Beall's old list, with some newer things thrown in.

I'm not saying that Frontiers in Neuroscience is not predatory, but its not a proper argument for it to be predatory, to point to a random list as proof. As Beall couldn't understand being crap publisher is not predatory in it self.

I think it’s funny to describe a drug as “street-quality” while using a slang term “heroic dose” in the same sentence.

That's fair, but research into psychoactive substances remains difficult due to legal constraints; N=1 but it will have piqued interest by others, they may want to repeat the tests on a larger scale.

That, or individuals will science on the ones they care for. I for one would write something like that down if I were to start developing dementia/alzheimers.

What does "the effects were very short lived" mean in this context? If it's hours then it seems useless, but if it's months that is short for us normies that expect to live decades more, but for someone who is 90+ that's a pretty nice percentage that is absolutely acceptable if it just means repeating the treatment.

please go find better resources over Rogan come on

The Johns Hopkins studies have been administering high doses for 20+ years now. The difference is that they use synthesized psilocybin instead of mushrooms (which makes the dosing more consistent since potency can vary a lot across strains and individual mushrooms).

5 grams isn't a high dose though, I'm not sure why it's described as such. Shops sell doses starting at 15g, although they recommend newbies take only half of that.

Example of a shop which describes 5g as a "light dose": https://www.sirius.nl/atlantis/

Sure, It’s a single case study so obviously take it with a grain of salt. Actual scientists understand this. People on social media don’t ands that’s annoying I get it.

On the other hand, it’s interesting and perhaps illuminating to people working in that field. A field mind you, that has made a little to no progress in decades. Arguments could be made they’ve made some errors and went down the wrong path. It’s a field that could probably use some new ideas.

It’s a single case study so obviously take it with a grain of salt. On the other hand, it’s interesting and perhaps illuminating to people working in that field. A field mind you, that has made a little to no progress in decades. Arguments could be made they’ve made some errors and went down the wrong path. It’s a field that could probably use some new ideas.

Not only that but the author has appeared on Joe Rogan - that tells me all I need to know.

Good criticism but be aware that acreditated authors and institutions are a bunch of crooks on the whole who cook their results, do p-hacking to the death, badly document their protocols, don't release their datasets not their analysis, and have no problems getting paid by big pharma and not disclosing it fully. The field is more joke than science at this stage.

Was that causation though? I have to imagine the kind of people who are open to psychedelics also generally oppose war.

On the other hand I heard a single dose does permanently increase your trait openness by a standard deviation, which is nuts. So maybe there is causation there too.

What’s exciting though is that this administration recently signed an executive order directing the agency to speed up the development and approval process for psychedelics.

I am immediately skeptical of anyone who goes on Rogan's show. Looking him up the guy has a PhD in education psychology, and his masters was in electrical engineering. I'm curious how much expertise he truly has on the subject and whether this was just spin for his company's work vs the natural option of psilocybin.

Not that I doubt the benefit of a non-psychoactive treatment. Just the adjacency of this idea to Rogan makes me immediately suspicious.

The problem with this study though is that it doesn’t really illuminate anything. Psychedelics restoring the default mode network in the brain is already somewhat understood (*that it happens, not the mechanism of how), so it’s not that strange a temporary reversion of the symptoms of Alzheimer’s would happen.

And it’s not even suggestive of eg making an actual medicine that could be taken long term, because Alzheimer’s physically destroys your brain. The restorative effect of psychedelics is just a bandage over not understanding why that damage is happening in the first place.

Unless it's a different Dean Radin, PhD, Wikipedia describes this guy as a psychic: https://en.wikipedia.org/wiki/Dean_Radin

Wow, if that turns out to work, that would alleviate lots of suffering for both the patient and her or his relatives and caretakers.

This would be pretty amazing.

It's not just 5 grams of some random cubensis, it's 5 grams of the enigma strain, which is ridiculously potent.

Yeah this story was on HN before a few weeks ago and I raised similar - it’s nuts to give that to someone who probably doesn’t have the mental state to be able to comprehend what is going on. Don’t understand how it is possibly ethical to do.

Especially with the effects being temporary - can you imagine how awful it must be to regain lucidity outside of your control and then lose it again for the sake of an experiment like this? Awful experiment.

If you have cared for someone with dementia, this isn't so surprising.

It isn't a monotonic decline with memories disappearing forever. It is like wave upon wave of changing capacity at different time scales. The general trend is deterioration, but there are frequent periods that can almost seem like remission.

There is a well known daily cycle referred to as "sundowning", where the sufferer tends to come unraveled later in the day. The next morning, they'll be more functional.

Later in the progression, you can see much higher frequency variations. Like periods of disorientation and confusion interspersed with periods of lucidity all within a single sitting or conversation.

In those periods of greater lucidity, recall of the past can be more accurate. General listening comprehension, speaking, and logical thought also seem more normal.

Edit to add: I sometimes wonder if the belief in terminal lucidity is one of those logical fallacies which support lots of superstitions. Are we just fixating on the final wave in this chaotic wave train, and forgetting all the other waves that happened before it? Or is it that more caretakers are engaged and observing these waves towards the end, e.g. because the patient is known to be in the terminal phase..?

While it’s a fairly good sized dose, it’s not one that would typically produce a nightmare trip scenario.

As far as ethics go, I would absolutely sign a document that gives the right for experimentation in the event I become incapacitated to some degree.

Same thing happens for other disease. Some kind of last honey moon period where your health improves and often followed by a catastrophic relapse.

I'm nobody but it makes me feels there's an economic system issue, the body gradually degrades but has the ability one last time to inject a final wave of change to try restore a proper state but the resources are too short and so the attempt cannot sustain itself.

I wonder if research is happening on this aspect.

It definitely wasn't causation, the causation flows the other way (criminalizing a proxy for a political belief as an end run around the first amendment).

> On the other hand, it’s interesting and perhaps illuminating to people working in that field

I responded to your other comment with this exact text, but to repeat:

This paper is not illuminating to people in the field. This is 3 unaffiliated people who paid to publish an anecdote without any supporting evidence. Paid medical journals are full of these.

Medical professionals know how to spot these claims because they’ve seen a hundred of them over the years that went nowhere. This was published not for the medical establishment, but for news media and social media and maybe to boost the author’s visibility to get funding for something they want to do.

Yeah, and a cure for cancer exists, but big pharma keeps it in a secret vault because treatments are more profitable than cures /s

I recently lost a family member to cancer, and had to go through this conspiracy bullshit from evil pieces of shit peddling snake oil to desprate people. Whatever rabbit holes your social media algorithms have led you down aren't healthy, friend. Clear your cookies and go touch grass.

> this administration recently signed an executive order directing the agency to speed up the development and approval process for psychedelics

Can’t the President directly unschedule it?

Because Trump is in bad need of this shit?

> On the other hand, it’s interesting and perhaps illuminating to people working in that field

People in medicine or research have seen hundreds of extraordinary case reports like this. They’re everywhere on different topics and they’re not hard to get published.

They know that extraordinary claims require extraordinary evidence and it’s easy to see that this paper is completely devoid of evidence, just some extraordinary claims written in formal medical language, minus the usual process, methodology, and assessments one would expect in a paper like this.

That's a silly statement. There's been plenty of people who went on there to try to talk sense into him.

Yup. Not sure which particular stopped-clock struck right within the generally anti-science MAHA movement but I think everybody is happy to take the win.

I’m a skeptical person to, you should be skeptical, it’s healthy! I just find guys like this super interesting and it was a really fun listen.

He talked about how his whole career he just followed whatever was most interesting to him at the time, hence the different disciplines. He also talked about programs he ran at universities where he was in charge of bringing different disciplines together & the challenges of that since academia is incredibly siloed. Departments don’t talk to each other.

So I think people like him are very valuable, since they aren’t afraid to think it if the box, work on taboo subjects like “psychic” abilities, and see the universe in novel ways.

He mentioned they’ve done trials in mice and chimpanzees with very positive results. I’m not saying it’s some crazy breakthrough or anything, but it’s interesting and something worth keeping an eye on. It sounded also like the killer feature is the nasal delivery tech. I don’t think the are the first ones to study non psychoactive psilocybin like compounds, but the nasal delivery that can cross into the brain directly seemed important.

And it's a single case which could simply be an anomaly. You'd need a serious controlled study to get any meaningful info about the effectiveness.

Very curious exactly who made the decision/gave permission to take granny on a shroom trip.

> Radin's paranormal ideas and work have been widely criticized by skeptic scientists and philosophers.

I'm not sure I'd trust this person for anything related to science.

> can you imagine how awful it must be to regain lucidity outside of your control and then lose it again for the sake of an experiment like this?

I would imagine the losing it again part is typically somewhat similar to how someone remembers a surgery under anesthesia -- they don't.

This is crackpot stuff - there's no scientific evidence of any of this, it's pure grifting. The individual cited above has a phd in educational psychology and runs a pseudoscience "institute"

Yeah and when they give it in experiments they also give participants an eye mask, which doesn't allow you to quickly snap back to reality. I enjoy Psilocybin, but that would be scary for me.

i’m skeptical how much of a real thing this is vs particularly type of appealing story to the human psyche

What an interesting take. I was imagining how precious one last conversation with a loved one would be.

> It isn't a monotonic decline with memories disappearing forever.

Last time I visited my grandpa he was really far gone. The day we arrived and subsequent two days he didn't even recognize his daughter, my mom, or even recall he had one. He'd sit in the bedroom and watch the garden, and ask "who's that guy" every 15 minutes or so, as he'd forget about me in the livingroom.

The last day we visited before flying home. I entered first, and this time he sat in the living room, and as he saw me enter the hallway he exclaimed my name. We reminisced for hours in fluent English, his third language and my second language, as I wasn't so good in his and my moms native language. He recalled lots of details, some even I had forgotten but I confirmed later.

He passed away a couple of weeks later.

I wouldn't, or put constraints into it - you may be incapacitated but you may also still be aware, and you wouldn't want to get I-have-no-mouth'd.

5+ grams is considered a "heroic dose", i.e. the one that is needed for ego death and subsequent therapeutic effects.

I'd love to see a before / after video of this or similar experiments, I'm really curious. I've seen similar ones for e.g. giving parkinsons' patients a dose of weed.

That's totally fair, and I'm often reminded not to paint all "Frontiers" journals with the same brush (although it's difficult for me sometimes).

AFAIK psychedelics are thought to stimulate neurons into connecting with each other more than they normally do - both temporarily (which explains the short-term sensations) and also permanently (they stimulate neuroplasticity).

Hey, fair enough. I don’t necessarily disagree with you, anything with psilocybin in the title tends to be a little more sensational. I find it very interesting though, I just listened to a recent Rogan podcast with Dr. Dean Radin, this exact case study came up because one of his companies is working a related product. Apparently they’ve developed a nasal delivery system that directly crosses into the brain, and the drug uses the same receptors as psilocybin but without the psychedelic effects. Apparently it has extraordinary positive effects on memory and lasts for months. They’ve tested on mice and chimpanzees, so real science is being done in this lane outside this case study. I guess I’m saying sometimes when “traditional” science gets stuck in the mud, we need creative & bold people who think outside the box to move things forward.

I’ve heard this is because a lot of symptoms are not from the disease itself but actually side effects of mounting an aggressive immune system response to the underlying condition. Once your body gives up the fight as a lost cause, you will get a burst of relief and restored function from the lack of immune activity but it happens just before total system collapse.

>>the government had a hysterical fit and completely banned it because people who took it were more likely to oppose the Vietnam War.

If you are to believe the Brave New World (https://en.wikipedia.org/wiki/Brave_New_World) worldview of Huxley (who topically was on loads of LSD himself), you'd think the government would want to flood the public with psychedelics -- low to zero toxicity, allows people to zone out, not addictive, allows people to focus inwards rather than focus on civic mismanagement.

Any ideas on why the US government is so opposed Psychedelics? Clearly the government is for Bread and circus. In fact, the establishment left and right want desperately for us to believe everything is indeed fine regardless of the facts our eyes see (e.g. Annie Lowrey on https://www.theatlantic.com/ideas/2026/05/americans-depresse...)

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.

It might be coincidence. Hiatal hernia affects more than 50% of the population over age 50, though not everyone shows symptoms.

>upper-esophageal sphincter dysfunction

If you've never read a Pulitzer Prize Winner, Confederacy of Dunces would be a personally-relatable disaster (to start with; it's great).

>Psychedelics are one of my favorite classes of drug.

Your initial description of usage was probably a bit wreckless, but I do maintain that most people would probably benefit from a single (or few) psilocybin experiences (preferably an initial high-dosage with a well-trained sitter).

Microdosing is a fantastic long-term strategy, before starting more-prescribed methodologies towards happiness. Probably not useful without an initial high-dosage, first (or much cloudier/ineffective).

YMMV £¢¢£

Rogan is obviously pro psychedelics, and was even featured in the oval office during the recent Ibogaine approval signing. I think it's worth noting if this N=1 "study" has any association with such an obviously biased and influential individual.

They only did it because it lets them beat the "big pharma is stealing from you (not us)" drum.

Ironic statement considering the last administration used terms like, "birthing people" and denied the existence of the president's dementia.

Keep the pathetic "pat me on the back" comments to Reddit please.

I saw it with a family member that had glioblastoma. It was weird, one of the nurses had seen it quite a few times apparently, it's also known as rallying. Family member's situation was similar to sibling comment's family, it wasn't right before death, just in the days and weeks leading up to it. It was like a sudden burst of vitality that came of nowhere, like their condition had dramatically reversed itself.

I'm sure it's a little different for everyone though.

Lost my grandfather to it in his late 80's. He did indeed become more responsive and engaged the day (maybe two) before he died, but he was non-verbal at that point. I recalled my mother telling me he was having a surprisingly good day on Sunday and seemed to recognize people, then getting the call from her the following evening that he had passed.

Ironically enough, the psychedelic field sort of defies some scientific analysis, so could be construed as "anti-science". I've seen some commentary that it's difficult to test. As an example, you can't really do a double blind study with a placebo because it's obvious to everybody who got the drug.

> MAHA

Make America Hallucinogenic Again?

that feeling of a clock striking right is actually a momentary glint of light pouring through a crack in the cold stone shell that has become encrusted around the hearts of those soaking too often in the type of extreme rhetorical panic which broods a curated and embedded fear similar to the kind that makes children afraid of the bogey man, they feel safer to stay hidden with the fear than to venture out enough to discover it was just a chimney sweep on the distant rooftop and everything is fine outside after all where they soon discover some great adventure or purpose in the richness of the world

It happened to my father, who was suffering a severe mental decline because of hydrocephalus. After weeks of trying to figure out what happened, one day he was sitting in the hospital perfectly fine, talking normally. I remember being so relieved. But then the next day he was back to not knowing anything and being half aware. He died a few weeks later.

Yeah well I was imagining how medical ethics work with respect to putting patients through unnecessary suffering. Temporarily restoring someone’s lucidity with the knowledge they will lose it again (having already suffered the progression of the disease the first time) is more helpful to you than it is to them

Raised with my grandmother with Alzheimer for all of my childhood she called me by her long dead brother's name.

Walked out the door one day said "See you later grandma" and she said "Have fun ______" and called me by my real name, called my older siblings and said go spend time, she died two days later.

Very common.

Psychededics are unpredictable. We know the government looked into their use as thought- and behavior-manipulating tools (MKUltra) but the results proved too chaotic. You might get a manchurian candidate...or the unabomber. But most likely just a renewed outlook on life.

Psyches basically raise the "temperature" (in machine learning parlance) of the brain, increasing crosstalk. This can jostle folks out of a mental rut. But it can also create positive feedback loops of upheaval.

Soma would only work as it did in BNW if society controlled essentially all sources of information - which is essentially the whole premise.

Oh right, that seems so logical..

> 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.

>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.

hallucinogens where taken by hippies, it was probably a way to put a few extra commies and lefties in prison

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.

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.

I mean.. I've seen the preliminary studies on treatment resistent PTSD so I'm also pro psychedelics, because I'm anti suicide.

Dismissing this "study" (really a case file) because of the N=1 and the shady journal seems like a stronger position than bringing in Rogan. Talking about Rogan just looks like partisan posturing.

Niacin works well as an 'active placebo'.

The same could be said for a lot of drugs that have strong side effects, just one difference here is the main "side effects" are something some people consider fun. Though you could still do double-blind for comparing the effectiveness of different psychedelics, e.g comparing LSD to Psilocybin.

Double blind studies became a requirement in order to protect the people from the greed of pharmaceutica companies and their natural desire to cut corners in research.

*Happy Again.

Microdosing has very limited evidence to support it, and even mode widely varying claims for what it supposedly helps with.

Ever since that episode I've had difficulty swallowing; sometimes when clearing my throat the air will unexpectedly blow out my mouth instead of my nose; and I also have to be doing that constantly because my throat never actually feels clear now; it sucks.

I used to be able to swallow gummy bears whole for fun. Or any medication, even huge pills (1g magnesium glycinate, for example -- those pills are not small) -- I didn't even need water. Now, even with water it's hard to swallow any medication, and it's hard to even swallow food half the time. Something definitely went wrong and is now wrong, compared to before.

I certainly have been reckless with it, but it helped me a lot to cope with constant high stress without resorting to more immediately harmful things. It also gave me a lot of nice experiences, unique insight and other things like that. Before this dysfunction started, bad experiences were pretty rare rather than practically every time...

just because it's not double blind doesn't mean it's not science though.

like idk, how do you do double blind studies of astronomical phenomena?

totally believe you, but i guess i feel like that is different from spontaneous temporary recovery from a long-term neurodegenerative disorder. i'm sorry for your loss.

Burma Shave

Yes, I think half of the politicians nowadays run on cocaine, no busts on TV.

> When you take it, you understand

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

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

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.

Such is natural when what one gets out of it is subjective, and there haven't been "real" academic studies on it yet. But, there is some consensus that it does seem to do something above placebo, even if all it does is say, lift spirits a little, or slightly increase creativity or neuroplasticity, etc.

If you're younger, having the condition is less likely, but it's possible you have a nonspecific injury that behaves similarly.

One weird trick to try is a "heel drop": https://www.modernapothecary.org/blog/the-healing-power-of-h... Even if you don't have a hernia, it can't hurt to try it; you can even do it accidentally by drinking a sports drink and then jogging around the block. I was shocked to find it ended an awful bout of laryngopharyngeal reflux. (I had a scan long ago that incidentally observed a sliding hiatal hernia, but I didn't have symptoms for many years.)

In any event, I'm sorry you're having this trouble, and I hope it resolves itself.

Yeah I know. I'm pulling that out as an example.

It's also true that people in the psychedelic world talk about non-reproducible aspects of the trip quite a bit. "Set and setting" and so forth.

> just because it's not double blind doesn't mean it's not science though.

Shhh, non-scientists don't know that.

why take cocaine when you can get your doctor to prescribe Adderall to you

shame, same with mushrooms?

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.

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

> 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.

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.

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

> 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-...

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.

Cannot say the same for psilocybin. Far as I can tell, I majorly overdosed the first time, because I fainted, hit my head and had to go to the hospital for staples.

Around a week later I took the same dose again (the rest of what I had) to help process the trauma. (It did help. I of course avoided the situation that made me faint the first time)

I'd want to try psilocybin again sometime; it's quite a bit more expensive than LSD but it does have an interesting profile (for me: less stimulant-like)

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.

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.