Improvement in advanced Alzheimer’s disease following high-dose psilocybin
frontiersin.org
frontiersin.org
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.
Can’t the President directly unschedule it?
So skipping it is a nuclear option that will not survive the courts
Make America Hallucinogenic Again?
like idk, how do you do double blind studies of astronomical phenomena?
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.
Shhh, non-scientists don't know that.
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...)
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.
Some of them are real, like becoming horrified by war. Other times the subjects think they've spoken with God. But I don't think they ever made anyone more pro-war.
Why do you think? Just watching a person off their tits on acid is unsettling if you've no idea whats caused it. And I would take LSD to "zone out", they aren't passive experiences like a joint, they are full day trips
The best elites can dream of is pharmaceutical levels, but even the most pure illegal stuff comes from a production line that's isolated from the rule of law and from transparency and liability and also likely from actual professionals, so it's likely still more toxic than it needs to.
The real "advantage" of cocaine is mostly that the molecule has an inherently stronger euphoric effect, I would assume (I've never taken it), also making it a worse therapeutic if you want to actually do a better job vs just feel "high".
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.
The more biological effects I agreed are not conclusion that can be drawn from that.
So it would actually be very surprising if it was just a clear net positive overall
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-...
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.
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.
It's because the drug is activating your reward centres, ideas are more likely to seem good etc. coke has a similar same effect.
> helping with depression Acid shrooms and the related mdma are all feel good drugs. Salvia on the other hand has no such feel good effect but is massively hallucinatory and perturbant. It helps with depression cos it's a feelgood drug.
To be fair, this is not how medical research is done.
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.
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.
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.
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.
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.
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.
If this is a real phenomenon, then it's amazing to think that at least some of the people who suffer from Alzheimer's still have their memories inside their minds, as opposed to the disease erasing the memories from existence, which means that an effective treatment might recover their identities.
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..?
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.
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.
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.
The day before he died, he climbed nimbly out of bed and did a little jig to show how spry he was.
Charming in its own way, although his lack of garments on his lower body (it made life easier as functions became less controlled) added a certain edginess to the event.
The phenomenon being discussed here is terminal lucidity. Hours or a day or two before passing.
I'm sure it's a little different for everyone though.
I remember it vividly because I got to tell her I love her and she smiled and said it back to me. She seemed to understand me for the first time in years.
It was short lived but I'm very grateful for that single exchange it gave me.
> 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.
There’s a reason the article includes “a case report” in the title.
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?
Even more interesting, Dr. Radin discussed one of his companies is working on a new drug that uses the same brain receptors as psilocybin, that has the potential to induce similar effects (with no psychedelic side effects) with a nasal delivery system that crosses directly into the brain. The benefit of that, he says, is the effect would last for much longer, months perhaps, and patients would only have to take it a few times per year.
Not that I doubt the benefit of a non-psychoactive treatment. Just the adjacency of this idea to Rogan makes me immediately suspicious.
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.
I'm not sure I'd trust this person for anything related to science.
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.
Very curious exactly who made the decision/gave permission to take granny on a shroom trip.
This would be pretty amazing.
That said, some relevant context here is that:
(1) Case studies are some of the most easily fabricated journal outputs
(2) This is published in Frontiers in Neuroscience, which is listed by some as being a predatory journal [0]. The Frontiers publishers are the fine folk who published an AI generated anatomical figure of a rat that not only was obviously incorrect to anyone you'd stop on the street, it'd give them nightmares [1].
So I'm not saying this paper is bunk, but that I reserve a healthy degree of skepticism pending some clinical trials or replication in animal models.
[0] https://www.predatoryjournals.org/news/list-of-all-frontiers...
[1] https://arstechnica.com/science/2024/02/scientists-aghast-at...
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.
> 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
Ethics statement
Ethical approval was not required for this single case report conducted in routine private clinical practice, in accordance with local legislation and institutional requirements. No experimental protocol or prospective research procedures were conducted. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report.
Medical doctors have a veeeeery wide leeway when it comes to the question of what they are allowed to do to patients. If nothing goes wrong or no one complains, pretty much everything goes - ethics reviews are only a thing for large-scale studies.
The exception tends to come from drug laws - in countries like Germany, for example, psilocybin is completely banned from manufacture, possession or prescription outside of highly regulated and specially permitted academic studies, but in countries with more relaxed attitudes, as a doctor you can do individual therapies as long as you find someone willing to pay for it.
In fact, that is a common issue with cancer and rare diseases. A bunch of therapies popular in that space run either with approved medication that gets used for another purpose or in higher/lower dosages (=off label treatment) or with completely new, untested and unapproved substances - that one was an issue here in Germany with a doctor inventing his own COVID vaccine, it ended up being dragged through the courts, with a recent acquittal [1] as the court considered this as an individual therapy.
[1] https://www.lto.de/recht/nachrichten/n/lg-luebeck-corona-imp...
They didn't even get consent from the person being drugged. That is absolutely insane.
It’s a case report (n=1) that a group of 3 people from Brazil wrote up and pushed into the publishing world. The report is full of big words and tables, but barely says anything more than the abstract: It’s basically “an 80 year old Japanese women received mushrooms and was better afterward” expanded with as much medical jargon as they could apply without accidentally getting too specific. No mention of how the Alzheimer’s disease history was documented or diagnosed or even if she was a patient of one of the authors.
I’m surprised how much it’s getting people to let their guard down and accept the result. Normally when studies get posted with only 100 to 500 participants the comments everywhere are full of doubters calling out the small sample size. For some reason this n=1 story written vaguely about extraordinary claims with a complete absence of pre-treatment documentation or standardize testing/scoring hits all the right notes to convince a lot of people that mushrooms can reverse Alzheimer’s disease.
I know it’s something that a lot of people would like to be true, but this is a domain where anyone in the world can make any claims they want and find a journal who will publish it if you pay them. People write and publish papers like this all the time claiming to have treated major diseases in a single patient or group of patients with different drugs or herbs.
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.
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.
I'm glad that psilocybin research is picking up. I really think its potential benefits deserve to be more widely known and available. Hopefully without the spontaneously appearing dysfunction though
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 £¢¢£
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)
That fainting episode wouldn't have been prevented with a guide unless they followed me into the bathroom, since for some reason the smell is what caused me to faint. (I found this out during the second time when going near the bathroom made me feel fainty -- I am glad I figured out what it was so that I could avoid it. It would've sucked to conclude that I can't have psilocybin at all, or something)
I will actually end up visiting the NL for other reasons eventually, so I might look into magic truffles :)
Datapoint: one.
----
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.
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.
> pay to publish journal
> no clear Alzheimers diagnosis ("[...] were considered clinically most compatible with advanced Alzheimer’s disease")
> administration of a heroic dose of street-quality drugs vs. a controlled sample
> no university or hospital affiliation?
Extraordinary claims require extraordinary evidence, hence I remain skeptical
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.
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.
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.
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.
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.
I would imagine the losing it again part is typically somewhat similar to how someone remembers a surgery under anesthesia -- they don't.
Example of a shop which describes 5g as a "light dose": https://www.sirius.nl/atlantis/
.5 grams to 1.5 grams is a mild experience.
For a personal example; I accidently did 9 grams of golden teacher, tripped balls, and woke up in the hospital with bruises and a cracked rib. It was not an enjoyable experience.
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.
People could use it as a treatment without having full mind blowing trips.
Meanwhile fentanyl is Schedule II. The government is often the biggest barrier to psilocybin research despite its positive effects being acknowledged for decades. Depending on the administration (which will sometimes signal they won't actually enforce the law) these research efforts are often terminated, meaning it is often safer/cheaper to just never start them in the first place.
https://www.dea.gov/drug-information/drug-scheduling
https://www.nature.com/articles/nrn3530
https://www.cato.org/blog/trumps-psychedelic-order-speeds-re...
> This case documents transient multidomain functional improvement in advanced Alzheimer’s disease following psilocybin administration. The findings do not imply disease reversal but suggest that residual functional capacity may persist in late-stage neurodegeneration and may become transiently accessible under specific neuromodulatory conditions.
Very interesting nonetheless.
> One month after the initial session, the patient remained continent and functionally improved compared with baseline. A second supervised psilocybin session using 3 g was subsequently performed and was associated with greater verbal expressivity, improved facial mimicry, spontaneous humor, emotionally valenced autobiographical imagery, and increased agility while walking.
> The patient spontaneously stated: “It is pleasant to come here.
This is just wonderful.