8 ms·

Improvement in advanced Alzheimer’s disease following high-dose psilocybin

224 points by cl3misch 4mo ago

kalyan258 4mo ago
[flagged]
UnfitFootprint 4mo ago
Good riddance - this kind of thing needs to be experimented with more. But 5 grams! This reads like witch doctor science; I’m surprised it passed ethics
- trio8453 4mo ago
  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).
- Aboutplants 4mo ago
  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.
  - Cthulhu_ 4mo ago
    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.
  - neonstatic 4mo ago
    5+ grams is considered a "heroic dose", i.e. the one that is needed for ego death and subsequent therapeutic effects.
- archonis 4mo ago
  It's not just 5 grams of some random cubensis, it's 5 grams of the enigma strain, which is ridiculously potent.
  - wouldbecouldbe 4mo ago
    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.
- dwroberts 4mo ago
  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.
  - bitmasher9 4mo ago
    What an interesting take. I was imagining how precious one last conversation with a loved one would be.
    - dwroberts 4mo ago
      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
  - kube-system 4mo ago
    > 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.
- WhyNotHugo 4mo ago
  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/ https://www.sirius.nl/atlantis/
  - tasty_freeze 4mo ago
    You must be talking wet weight. 5g of dry mushrooms is about 50mg of psilocybin, which has been referred to as a "heroic dose" for decades.
  - ChoGGi 4mo ago
    5 grams is what most people especially those new to mushrooms would call an intense experience. .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.
- foobarbecue 4mo ago
  "good riddance"? What went away?
trio8453 4mo ago
Not quite a "successful treatment": > 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.
- Cthulhu_ 4mo ago
  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.
- trumpdong 4mo ago
  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).
sva_ 4mo ago
> n=1 > 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
- Cthulhu_ 4mo ago
  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.
- 40four 4mo ago
  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.
  - Aurornis 4mo ago
    > 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.
- fred_is_fred 4mo ago
  Not only that but the author has appeared on Joe Rogan - that tells me all I need to know.
40four 4mo ago
This exact case study came up on a recent Rogan episode with Dean Radin, PhD. While the result is very interesting and perhaps illuminating about the unexpected biological mechanisms, apparently the effects were very short lived. 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.
- mc32 4mo ago
  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.
  - turtlesdown11 4mo ago
    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"
    - mc32 4mo ago
      That's quite unfortunate. The victims and relatives of the victims of this disease are looking for any sliver of hope to ease the horrible path it takes so people like this who give false hope are truly degenerate, despicable beings. Like the people who took advantage of Farrah Fawcett's condition.
- drakythe 4mo ago
  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.
Aurornis 4mo ago
This case report is being shared widely across social media but it’s full of red flags from top to bottom. 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.
- 40four 4mo ago
  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.
  - Aurornis 4mo ago
    > 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.
trumpdong 4mo ago
Psilocybin is one of those things we don't even know the full effects of because the government had a hysterical fit and completely banned it because people who took it were more likely to oppose the Vietnam War.
- Aurornis 4mo ago
  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.
  - rerx 4mo ago
    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 4mo ago
      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.
ChrisArchitect 4mo ago
Previously: https://news.ycombinator.com/item?id=48420481 https://news.ycombinator.com/item?id=48420481
jszymborski 4mo ago
So, I'm not making any accusations or decelerations of "bad science", I've only read the abstract and this isn't my field. 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-predatory-journals https://www.predatoryjournals.org/news/list-of-all-frontiers... [1] https://arstechnica.com/science/2024/02/scientists-aghast-at-bizarre-ai-rat-with-huge-genitals-in-peer-reviewed-article/ https://arstechnica.com/science/2024/02/scientists-aghast-at...
- tokai 4mo ago
  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.
  - jszymborski 4mo ago
    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).
- repple 4mo ago
  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
LoganDark 4mo ago
Psychedelics are one of my favorite classes of drug. I used to take LSD recreationally every few weeks or months, until one bad vomiting episode caused me upper-esophageal sphincter dysfunction somehow. Ever since then, I can't seem to take any without throwing up (and generally having a terrible time due to stomach contents backing up into my throat constantly). Nobody can seem to figure out why my throat stopped working properly all of a sudden or how to fix it. :( 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
- sowbug 4mo ago
  It might be coincidence. Hiatal hernia affects more than 50% of the population over age 50, though not everyone shows symptoms.
  - LoganDark 4mo ago
    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.
    - sowbug 4mo ago
      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-heel-drops-for-hiatal-hernia-enhanced-with-water/ 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.
Teknomadix 4mo ago
Highly editorialized title. "Transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration: a case report" This is exactly that. A case report. This is not a successful treatment. Far short of that.
- gchamonlive 4mo ago
  > 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.
  - dpark 4mo ago
    The title is misleading. “Improvement in advanced Alzheimer’s disease following high-dose psilocybin” sounds like results from a broader study, not an anecdotal report. There’s a reason the article includes “a case report” in the title.
    - gchamonlive 4mo ago
      It might be inappropriate for the target audience because they might mistake the treatment for the protocol, but it's not trying to be misleading I think. In any case the title got editorialised which I think settles this.
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sowbug 4mo ago
I was recently reading about a phenomenon called terminal lucidity, where a person suffering from mental decline such as Alzheimer's spontaneously improves, recognizing loved ones, retrieving memories, and being able to carry on conversations. It's called "terminal" because the person usually dies within hours or days. 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. https://en.wikipedia.org/wiki/Terminal_lucidity https://en.wikipedia.org/wiki/Terminal_lucidity
- whimsicalism 4mo ago
  i’m skeptical how much of a real thing this is vs particularly type of appealing story to the human psyche
  - deleted 4mo ago
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  - shepardrtc 4mo ago
    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.
    - whimsicalism 4mo ago
      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.
    - markdown 4mo ago
      I'm sorry but it didn't happen to him. The phenomenon being discussed here is terminal lucidity. Hours or a day or two before passing.
emsign 4mo ago
The key are the post-synaptic serotonin receptors. If the drug is able to reach them, these receptors trigger axons making new connections to other neurons.
hmokiguess 4mo ago
If it was my grandma I would treat her to some shrooms, I've taken them many times and I find them quite safe, I can't see harm in trying. If it would really works I don't know, but I would find value in the experience and consider it safe. Though the challenge would be explaining it to her and potentially dealing with her tripping.
godwinson__4-8 4mo ago
Reminder that the American federal government classifies psilocybin as a Schedule I drug "no currently accepted medical use and a high potential for abuse". Along with marijuana. And heroin. Who else but the DEA thinks those three things make sense to put in the same bucket? 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.dea.gov/drug-information/drug-scheduling https://www.nature.com/articles/nrn3530 https://www.nature.com/articles/nrn3530 https://www.cato.org/blog/trumps-psychedelic-order-speeds-research-not-access https://www.cato.org/blog/trumps-psychedelic-order-speeds-re...
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kazinator 4mo ago
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brgsk 4mo ago
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tasty_freeze 4mo ago
How is this ethical? The ethics section of the summary simply asserts it was OK, but I don't see how this being done in a private practice excuses them from normal strictures. They say this wasn't an experimental protocol, nor research, so I guess they dosed grandma for shits and giggles? 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.
- 12_throw_away 4mo ago
  Not to comment on the overall ethical situation (dunno what constitutes informed consent for an alzheimer's patient in Brazil, presumably it involves some legal guardian), but this is a doctor reporting on an individual treatment of their patient. It is not a research study. Doctors have wide latitude in treating their own patients, they do not require board approval to do so.
- mschuster91 4mo ago
  > They say this wasn't an experimental protocol, nor research, so I guess they dosed grandma for shits and giggles? 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-impfung-aktion-stoecker-strafprozess-freispruch-revision https://www.lto.de/recht/nachrichten/n/lg-luebeck-corona-imp...
ChoGGi 4mo ago
5 grams of enigma? Goddamn that's a pretty intense trip, hope they played some mellow music at least.
hoppp 4mo ago
I wonder if the positive effects still happen if the psychedelic trip is interrupted with a benzo? People could use it as a treatment without having full mind blowing trips.

224 points by cl3misch 4mo ago

[flagged]

Good riddance - this kind of thing needs to be experimented with more. But 5 grams! This reads like witch doctor science; I’m surprised it passed ethics

trio8453 4mo ago
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).
Aboutplants 4mo ago
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.
- Cthulhu_ 4mo ago
  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.
- neonstatic 4mo ago
  5+ grams is considered a "heroic dose", i.e. the one that is needed for ego death and subsequent therapeutic effects.
archonis 4mo ago
It's not just 5 grams of some random cubensis, it's 5 grams of the enigma strain, which is ridiculously potent.
- wouldbecouldbe 4mo ago
  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.
dwroberts 4mo ago
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.
- bitmasher9 4mo ago
  What an interesting take. I was imagining how precious one last conversation with a loved one would be.
  - dwroberts 4mo ago
    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
- kube-system 4mo ago
  > 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.
WhyNotHugo 4mo ago
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/ https://www.sirius.nl/atlantis/
- tasty_freeze 4mo ago
  You must be talking wet weight. 5g of dry mushrooms is about 50mg of psilocybin, which has been referred to as a "heroic dose" for decades.
- ChoGGi 4mo ago
  5 grams is what most people especially those new to mushrooms would call an intense experience. .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.
foobarbecue 4mo ago
"good riddance"? What went away?

trio8453 4mo ago

Not quite a "successful treatment": > 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.

Cthulhu_ 4mo ago
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.
trumpdong 4mo ago
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).

sva_ 4mo ago

> n=1 > 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

Cthulhu_ 4mo ago
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.
40four 4mo ago
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.
- Aurornis 4mo ago
  > 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.
fred_is_fred 4mo ago
Not only that but the author has appeared on Joe Rogan - that tells me all I need to know.

40four 4mo ago

This exact case study came up on a recent Rogan episode with Dean Radin, PhD. While the result is very interesting and perhaps illuminating about the unexpected biological mechanisms, apparently the effects were very short lived. 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.

mc32 4mo ago
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.
- turtlesdown11 4mo ago
  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"
  - mc32 4mo ago
    That's quite unfortunate. The victims and relatives of the victims of this disease are looking for any sliver of hope to ease the horrible path it takes so people like this who give false hope are truly degenerate, despicable beings. Like the people who took advantage of Farrah Fawcett's condition.
drakythe 4mo ago
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.

Aurornis 4mo ago

This case report is being shared widely across social media but it’s full of red flags from top to bottom. 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.

40four 4mo ago
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.
- Aurornis 4mo ago
  > 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.

trumpdong 4mo ago

Psilocybin is one of those things we don't even know the full effects of because the government had a hysterical fit and completely banned it because people who took it were more likely to oppose the Vietnam War.

Aurornis 4mo ago
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.
- rerx 4mo ago
  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 4mo ago
    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.

ChrisArchitect 4mo ago

Previously: https://news.ycombinator.com/item?id=48420481 https://news.ycombinator.com/item?id=48420481

jszymborski 4mo ago

So, I'm not making any accusations or decelerations of "bad science", I've only read the abstract and this isn't my field. 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-predatory-journals https://www.predatoryjournals.org/news/list-of-all-frontiers... [1] https://arstechnica.com/science/2024/02/scientists-aghast-at-bizarre-ai-rat-with-huge-genitals-in-peer-reviewed-article/ https://arstechnica.com/science/2024/02/scientists-aghast-at...

tokai 4mo ago
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.
- jszymborski 4mo ago
  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).
repple 4mo ago
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

LoganDark 4mo ago

Psychedelics are one of my favorite classes of drug. I used to take LSD recreationally every few weeks or months, until one bad vomiting episode caused me upper-esophageal sphincter dysfunction somehow. Ever since then, I can't seem to take any without throwing up (and generally having a terrible time due to stomach contents backing up into my throat constantly). Nobody can seem to figure out why my throat stopped working properly all of a sudden or how to fix it. :( 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

sowbug 4mo ago
It might be coincidence. Hiatal hernia affects more than 50% of the population over age 50, though not everyone shows symptoms.
- LoganDark 4mo ago
  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.
  - sowbug 4mo ago
    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-heel-drops-for-hiatal-hernia-enhanced-with-water/ 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.

Teknomadix 4mo ago

Highly editorialized title. "Transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration: a case report" This is exactly that. A case report. This is not a successful treatment. Far short of that.

gchamonlive 4mo ago
> 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.
- dpark 4mo ago
  The title is misleading. “Improvement in advanced Alzheimer’s disease following high-dose psilocybin” sounds like results from a broader study, not an anecdotal report. There’s a reason the article includes “a case report” in the title.
  - gchamonlive 4mo ago
    It might be inappropriate for the target audience because they might mistake the treatment for the protocol, but it's not trying to be misleading I think. In any case the title got editorialised which I think settles this.
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sowbug 4mo ago

I was recently reading about a phenomenon called terminal lucidity, where a person suffering from mental decline such as Alzheimer's spontaneously improves, recognizing loved ones, retrieving memories, and being able to carry on conversations. It's called "terminal" because the person usually dies within hours or days. 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. https://en.wikipedia.org/wiki/Terminal_lucidity https://en.wikipedia.org/wiki/Terminal_lucidity

whimsicalism 4mo ago
i’m skeptical how much of a real thing this is vs particularly type of appealing story to the human psyche
- deleted 4mo ago
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- shepardrtc 4mo ago
  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.
  - whimsicalism 4mo ago
    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.
  - markdown 4mo ago
    I'm sorry but it didn't happen to him. The phenomenon being discussed here is terminal lucidity. Hours or a day or two before passing.

emsign 4mo ago

The key are the post-synaptic serotonin receptors. If the drug is able to reach them, these receptors trigger axons making new connections to other neurons.

hmokiguess 4mo ago

If it was my grandma I would treat her to some shrooms, I've taken them many times and I find them quite safe, I can't see harm in trying. If it would really works I don't know, but I would find value in the experience and consider it safe. Though the challenge would be explaining it to her and potentially dealing with her tripping.

godwinson__4-8 4mo ago

Reminder that the American federal government classifies psilocybin as a Schedule I drug "no currently accepted medical use and a high potential for abuse". Along with marijuana. And heroin. Who else but the DEA thinks those three things make sense to put in the same bucket? 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.dea.gov/drug-information/drug-scheduling https://www.nature.com/articles/nrn3530 https://www.nature.com/articles/nrn3530 https://www.cato.org/blog/trumps-psychedelic-order-speeds-research-not-access https://www.cato.org/blog/trumps-psychedelic-order-speeds-re...

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kazinator 4mo ago

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brgsk 4mo ago

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tasty_freeze 4mo ago

How is this ethical? The ethics section of the summary simply asserts it was OK, but I don't see how this being done in a private practice excuses them from normal strictures. They say this wasn't an experimental protocol, nor research, so I guess they dosed grandma for shits and giggles? 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.

12_throw_away 4mo ago
Not to comment on the overall ethical situation (dunno what constitutes informed consent for an alzheimer's patient in Brazil, presumably it involves some legal guardian), but this is a doctor reporting on an individual treatment of their patient. It is not a research study. Doctors have wide latitude in treating their own patients, they do not require board approval to do so.
mschuster91 4mo ago
> They say this wasn't an experimental protocol, nor research, so I guess they dosed grandma for shits and giggles? 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-impfung-aktion-stoecker-strafprozess-freispruch-revision https://www.lto.de/recht/nachrichten/n/lg-luebeck-corona-imp...

ChoGGi 4mo ago

5 grams of enigma? Goddamn that's a pretty intense trip, hope they played some mellow music at least.

hoppp 4mo ago

I wonder if the positive effects still happen if the psychedelic trip is interrupted with a benzo? People could use it as a treatment without having full mind blowing trips.