21 ms·

Psilocybin desynchronizes the human brain

273 points by kieckerjan 2y ago

sowut 2y ago
incredibly powerful drug. we should be training a legion of mystics using psilocybin instead of criminalizing it and obfuscating the implications of its use
- worik 2y ago
  > training a legion of mystics Oh yeah! But what does that mean?
  - RALaBarge 2y ago
    Well, we would need the mystics to figure that out for us.
    - sowut 2y ago
      it's not that complex
  - wlonkly 2y ago
    It means a lot of them!
  - sowut 2y ago
    it means regimented deep psychedelic experiences with focus on particular skills whether it be programming, music, art, writing, or any particular focus area. the results to be discussed, studied, understood, appreciated. almost like a college of psychedelics.
- antegamisou 2y ago
  You're like 70 years late https://en.wikipedia.org/wiki/MKUltra https://en.wikipedia.org/wiki/MKUltra Project MKUltra was an illegal human experiments program designed and undertaken by the U.S. Central Intelligence Agency (CIA) to develop procedures and identify drugs that could be used during interrogations to weaken people and force confessions through brainwashing and psychological torture. [...] The project studied the effects of psychoactive drugs, particularly LSD, psilocybin, mescaline, cocaine, AMT and DMT on people
  - sowut 2y ago
    except that was a secret government program and humans were used as guinea pigs. that's not what i'm talking about at all
jiveturkey 2y ago
> MEQ30 Mystical Experience Questionnaire
- jkingsman 2y ago
  See more info here: https://psychology-tools.com/test/meq-30 https://psychology-tools.com/test/meq-30
jklinger410 2y ago
[flagged]
- herodoturtle 2y ago
  I read this and it instantly “clicked” - thank you for the analogy. I must ask, is this based on scientific evidence?
  - haswell 2y ago
    Not the parent, but my understanding is that the effects have a lot to do with the brain entering a short term state of neuroplasticity at a level that is not normally experienced in adulthood. The result being that processing emotions and making key realizations actually “stick”. It’s possible for example as someone who suffers from PTSD to realize that it’s no longer necessary to be on high alert, but the body is anyway. I’m also no expert so take this with a grain of salt, but I think it’s less of a defragmentation and more of an increase in pliability that leads to lasting changes. This is one of the reasons that Psylocibin-assisted therapy is showing such promising results. The brain entering that state unguided may or may not lead to good results. But when a trained therapist is involved, outcomes improve.
  - jkingsman 2y ago
    This study would certainly seem to indicate that this is at least true in some form — the study shows that parts of the brain that are typically very well correlated with each other (one fires then the other fires, or they fire together) come uncoupled from each other under the influence of psilocybin. I'm not sure it could be correctly stated in the gross sense as "jumbling it up and making it re-build," but there certainly is a shift in how the brain's components work together for the duration of the drug's effects, per this study.
- deleted 2y ago
  [deleted]
- Obscurity4340 2y ago
  Do you know similar stuff about dissociatives, like NMDA-antagonists? Are their effects in any way comparable or is it completely different net results?
jkingsman 2y ago
This concerns Functional Connectivity[0], which is basically a measure of how temporally correlated regions are; those that fire in sync or in a strongly correlated pattern are functionally connected. Essentially, the TL;DR of this study is that psilocybin's 5-HT2A agonism seems to reduce synchronized FC activity not just in neurons but the whole brain: psilocybin makes parts of the brain overall that otherwise work together (in a time-correlated sense) stop displaying time-correlation. These results were seen most in the Default Mode[1] network, which is more or less the brain system in operation when you are inside your head — daydreaming, thinking, remembering, etc. — as opposed to processing visual cues or observing the physical world. [0]: https://en.wikipedia.org/wiki/Dynamic_functional_connectivity https://en.wikipedia.org/wiki/Dynamic_functional_connectivit... [1]: https://en.wikipedia.org/wiki/Default_mode_network https://en.wikipedia.org/wiki/Default_mode_network — this article is one of those that just blows my mind clean out my ears (heh); the brain is such a wonder.
- jppittma 2y ago
  I think the fact that nobody knows how to deal with negative correlations in functional connectivity takes away from the validity of the whole concept. People literally throw out negatively correlated voxels/ROI's. This, on top of the fact that functional connectivity is only related to physical connectivity in the abstract. (it's about the correlated time series activity in pixels over time, and isn't bound by any cellular connectivity). I just struggle to discern any meaning from the concept.
  - free_energy_min 2y ago
    any source that mentions throwing away negative correlations?
    - parpfish 2y ago
      It’s commonly done in fMRI studies and I always got the impression it was less about not being able to understand negative relationships (e.g., it’s well understood that things like the default mode network is inversely related to active processing) and it’s more about not being clear how to use negative values as edge weights in graph theoretic analysis of networks
trumps-ear-bug 2y ago
This can be a good thing, to reboot your brain
notnaut 2y ago
While the analogies are often useful, everyone reading HN comments should be very aware and very skeptical of just how often computer/tech people rely on computer/tech analogies to understand things that are fundamentally not computers/tech. It is very very easy for smart people with functionally specific jobs/hobbies/ways of thinking to see all reality through that narrow window. It often leads to important details being glossed over or entirely missed. The more self-confident ones quickly start seeing the analogies as fundamental facts, usually with negative consequences like loss of empathy or a tendency to see big picture generalizations as specific universal truths. Mushrooms have had a similar effect on me at times. You can start feeling like you KNOW big sweeping Truths. Similar to religiously “knowing” something. And that feeling of knowing is hard to overcome. But it is just a feeling.
- codr7 2y ago
  I would argue it's way more meaningful... It's unconscious knowledge; maybe not ready to hit the surface yet, but still actively affecting your life from within. Whatever glimpses you get is just what you're capable of dealing with atm. Everybody's experience is different.
  - stvltvs 2y ago
    It might clarify things to say unconscious beliefs, expectations, or thought patterns instead of knowledge. It doesn't seem that the subconscious mind is a font of pure wisdom and knowledge but it powerfully affects us in ways that our conscious mind isn't aware of, by definition. Before using psychedelics, it's important to anchor ourselves by questioning the difference between knowing something and feeling like we know something.
    - mock-possum 2y ago
      One thing that a lot of people struggle with is seeing their feelings as ‘just’ feelings - it’s got to be something to do with our biology, where we instinctively seek out and cling to answers for why we feel a certain way - to justify our feelings I guess - instead of recognizing them as ‘just’ feelings, and seeing that instinct for what it is - ‘blind’ instinct that can easily seduce us into false beliefs.
philip1209 2y ago
Cool paper. I know some tech people have been donating to psilocybin research - is there any apparent connection to this study?
- jdietrich 2y ago
  No. https://www.nature.com/articles/s41586-024-07624-5#Ack1 https://www.nature.com/articles/s41586-024-07624-5#Ack1
TechDebtDevin 2y ago
PSA: My buddy shot himself in the head while we were on shrooms in our twenties. He thought he meant God, took a shower picked up a gun and shot himself in the head. While I've had trips since then and do get benefits from those experiences. People without experience should be careful, especially if you have a history of mental illness. He did have a history to some degree but not overtly.
- JohnMakin 2y ago
  [flagged]
  - stvltvs 2y ago
    I think what you said is compatible with OP. It urged caution, not prohibition.
  - bogota 2y ago
    You don’t need to be a doctor or therapist to let people know that some people can have very bad reactions and it’s not all roses. I see the same thing happening in people smoke marijuana where any claim that it can have harmful effects for some or with abuse is met with “yeah well what do you know, i read this other thing and i never had issues myself”.
    - JohnMakin 2y ago
      It seems to me that in this case the issue was someone out of their mind high on shrooms had immediate access to a gun, not the “mentally ill person does drugs and dies” trope which is quite tired and I’m pretty sure not backed by any kind of science. I only posted my reply because comments like these add to the stigma of mental illness and may make people who are suffering less willing to try these types of treatments.
      - darkerside 2y ago
        This observation of fact is more interesting and nuanced than your initial defensive reaction
lawlessone 2y ago
>Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6–12 months later. Not simultaneously I hope.. that sounds like it would be a rough ride
- jkingsman 2y ago
  No, they were separate dosages to compare FC effects.
- titanomachy 2y ago
  "[methylphenidate] was selected as the active control condition to simulate the cardiovascular effects and physiological arousal (that is, controlling for dopaminergic effects) associated with psylocybin"
- brotchie 2y ago
  "it can generally be assumed that there is approximately 15 mg (+/- 5 mg) of psilocybin per gram of dried mushroom" -Wikipedia So 25mg is ~1.5g of dried mushrooms. Decent dose, but not a "omg I'm one with the universe." For instance, a "Hero Dose" typically starts at 5g of dried mushrooms, so ~3x the dosage used in the study. Though it's possible the uptake rate using their dosing mechanism is much higher than "stomach acid digested dried mushrooms."
  - mistrial9 2y ago
    some kinds of mushrooms can grow tolerance fairly quickly, also.. based on info from a friend
  - newzisforsukas 2y ago
    > So 25mg is ~1.5g of dried mushrooms. 1.25g - 2.5g *
    - collyw 2y ago
      That isn't a high dose. Medium.
poikroequ 2y ago
Reading this feels an awful lot like watching the video about the retro encabulator.
empath75 2y ago
I can't think of anything in the world I would enjoy doing less than completing "a simple auditory–visual matching task" while in an MRI scanner on shrooms.
- kjkjadksj 2y ago
  The set and settings researchers typically use for usual psych studies are going to bias psychedelic results so much. Think that building you hated in undergrad's crusty unlit cinderblock basement with no windows but coated in cameras and microphones. Its so dystopian, you are literally a caged rat. I don't think you can perform this research in good faith without having experienced a proper trip yourself. It's just impossible to put into words much less gleam any actual understanding from written description of it. Science needs more Albert Hoffman's who are willing to couple their knowledge with this experience without fear of being fired from IRB violation and ostracized by the scientific community. Otherwise we will forever be grasping in the dark with these drugs.
  - titanomachy 2y ago
    gleam -> glean
    - kjkjadksj 2y ago
      Too late to edit :(
  - dylan604 2y ago
    I would suggest the world needs more Shulgins as well. https://en.wikipedia.org/wiki/Alexander_Shulgin https://en.wikipedia.org/wiki/Alexander_Shulgin
  - gorlilla 2y ago
    I've never had a good trip indoors. My brain has a knack for staying grounded by familiar settings, so I hardly even experience the trip. Put me outdoors in the dark and my brain can be stimulated by natural sounds which are not nearly as predictable as those I find indoors. I think it has to do with processing stimuli that I can't instantly attribute to something I know very well. I am also normally hypervigilant, which may come into play since I think familiar settings inhibit my ability to fall under the effects of intoxication somewhat. I am also much more likely to try and sleep off any overwhelming feelings if I'm in the aafety/comfort of a house vs the middle of the forest. Setting doesn't necessarily mean the 'safest' space for you since my own home negatively effects the overall experience. Having someone who is experienced, sober and willing to guide you for hours (lots of trust) is crucial since the opti.al setting may not be the safest setting. TL;DR - I struggle to trip or even enjoy a trip indoors. I have always felt shrooms work best when you let them help you attune to nature. Listening to the wind, trees, insects, etc... it's like washing your eyeballs with kittens.
Unbefleckt 2y ago
While it's amusing in the short term, the long term side effects for me were awful. I felt like my brain was slow and unfocused, I was no longer quick in conversation or able to concentrate as well as usual, I felt disconnected from myself, sort of like when you recall a memory so old that it seems like it belongs to someone else, I had a headache for almost 3 weeks. Throwing this in here as there are a fair few "dude just take drugs" comments and worry they might be the religious types.
- cthalupa 2y ago
  That's interesting, because I don't that anyone really has reported these side effects and I don't believe there are any known pharmacological effects from psilocybin or psilocin that would cause any of that. Were they dried mushrooms you ate? Do you trust the provenance of them? If they were a chocolate bar or similar, many of those do not actually have psilocybin or psilocin in them, and are instead using a variety of different research chemicals that are significantly less understood. If it was dried mushrooms, there are a variety of species that induce hallucinogenic effects through other chemicals than what you find in your usual magic mushrooms. They might have been regular shrooms, of course - people react to things differently - but that's a different enough outcome that I wonder if it wasn't something else entirely.
  - newzisforsukas 2y ago
    > I don't believe there are any known pharmacological effects from psilocybin or psilocin that would cause any of that What are your qualifications to make a claim like that? There hasn't been much clinical research in humans using psilocybin until very recently [1], and they certainly do not cover the range of different species of mushrooms that contain the alkaloids [2]. 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016263/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016263/ 2. https://en.wikipedia.org/wiki/List_of_psilocybin_mushroom_species https://en.wikipedia.org/wiki/List_of_psilocybin_mushroom_sp...
    - cthalupa 2y ago
      My qualifications for saying "I don't believe there are any known effects that match that" is... reading quite a lot of clinical research on their usage, and not having seen anything that would match those effects. You'll notice I qualified that statement in two ways - both that it is limited to my personal understanding and that of 'known' effects. I'm not really sure what you're arguing - neither of these links indicate otherwise. Are you familiar with the null hypothesis? Unless we have evidence of something being the case, why would we think it would be the case? We also have decades of anecdotal reports on usage of psilocybin and psilocin containing mushrooms and I'm also not aware of any significant evidence from that that such an effect is even remotely common - it's the first I've ever encountered that sort of story about persistent headaches for multiple weeks following their usage.
deleted 2y ago
[deleted]
trallnag 2y ago
LSD is better, sorry :/
- GuB-42 2y ago
  Psilocybin and LSD are both psychedelics and 5-HT2A agonists. Even though the study uses psilocybin, the findings should apply to LSD too.
  - xk_id 2y ago
    Not really. Two ligands of the same receptor can have very different effects. There are 5ht2a agonists who don’t even cause perceptual effects. Besides, LSD has activities at several other receptors as well, which contributes to its effect. Extrapolation of biological effect based on the receptor affinity of a ligand is a pretty crude hypotheses.
    - GuB-42 2y ago
      I am not inventing this, it is what the study itself suggests. > To determine whether this reflects a common effect of psilocybin that generalizes across datasets and psychedelics, we calculated dimension 1 scores for extant datasets from participants receiving intravenous (i.v.) psilocybin55 and lysergic acid diethylamide (LSD)56. Psychedelic treatment increased dimension 1 in nearly every participant in the psilocybin and LSD datasets (Fig. 2c), suggesting that this is a common effect across psychedelic drugs and individuals.
- kinakomochidayo 2y ago
  Probably depends on your objective. Mushrooms are much gentler and forgiving than LSD when it comes to traumas.
mike_ivanov 2y ago
It's interesting that brain hypersynchronicity is a known source of epileptic seizures (among other things). This potentially could be a treatment for this specific problem. See e.g. * https://www.sciencedirect.com/science/article/pii/S089662731930964X * https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2010.02805.x
- greentxt 2y ago
  Doubtful. Shrooms cause seizures.
  - CacheRules 2y ago
    Sources?
    - __MatrixMan__ 2y ago
      Anecdotal, but I've tripped with two people who showed seizure like symptoms that they never had before or since. Couldn't find any data at the time. Tried to get them to submit experience reports on erowid so that there would be some data out there, but they didn't want to put anything about it in writing.
      - mistrial9 2y ago
        ok - an underweight 20 year old woman who did not eat well before a Rolling Stones concert and then used cocaine and alcohol, also had a seizure. goddam Mick Jagger !
      - foobiekr 2y ago
        Are you sure shrooms? If chocolates or gummies the compound therein is not quite the same as recent news stories have noted.
        __MatrixMan__ 2y ago
        Yeah, I grew them. I didn't sequence them for identification, but they were phenotypically P. Cubensis, as advertised on the spore syringe. In neither case was it a big deal in the long run (not exactly great vibes in the short term though). I used to be a pretty enthusiastic user, so "just two times" is indeed uncommon. Hopefully with the recent trend of decriminalization we can get together some respected data about this sort of thing. I still believe that psilocybin has been a net positive thing for most people who have tried it (including these two cases). Even if the seizure thing were confirmed, all the conventional wisdom re: tripping remains unchanged. Be in a safe place with trusted people, consider a trip sitter, etc. On the other hand, I think having the data might help drive some better decisions: Situations you might avoid (e.g. swimming), etc.
motohagiography 2y ago
Feedback in an anlog signalling system producing delays, reflections, geometric and clipped artifacts is something anyone who has used a guitar effects pedal is familiar with. I have a surprising number of old comments on this site about how hallucinogens just impair signalling and the results are geometric for the same reasons. This article says it impairs the equivalent to the CLK signal, which sounds just about right. Don't be disappointed about it not being another spiritual dimension, they discovered we literally have effects pedals for our brains. This is the coolest thing ever. We could probably classify hallucinogenic artifacts by chorus, delay, flange, harmonics...
- l33tbro 2y ago
  The problem is getting so out of it that you can't reach the wet/dry knob to dial back the wacko.
- cmehdy 2y ago
  Paychonautwiki has been classifying effects in a somewhat similar fashion for years/decades now: https://psychonautwiki.org/wiki/Geometry https://psychonautwiki.org/wiki/Geometry
RamblingCTO 2y ago
Lots of people have a lot of negative stuff to say, but my take is: if you do psychedelics, you need to do the work and you need a firm ground before that. We have research that it might help with PTSD, depression, etc. but it's not like you just take it and you're done. It's a powerful substance and with power comes responsibility. I like to think of it more as an enhancer as to what's inside your head anyways. If that's fucked already, how are psychedelics gonna help you?
- zild3d 2y ago
  > We have research that it might help with PTSD, depression, etc. but it's not like you just take it and you're done. Worth noting the research is on psilocybin with supportive psychotherapy, not just take some mushrooms you got from a guy and have at it. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2020/11/psychedelic-treatment-with-psilocybin-relieves-major-depression-study-shows https://www.hopkinsmedicine.org/news/newsroom/news-releases/...
  - RamblingCTO 2y ago
    Exactly what I was thinking about! There are some nice studies being done in Switzerland with a trip + 7 (I believe) sessions before and after
  - kazinator 2y ago
    So, take some mushrooms from a guy, lie down on the couch, and tell him about your mother.
  - Litost 2y ago
    There's a good documentary about the John Hopkins research on treating drug resistant depression with psilocybin which unfortunately isn't available any more via the BBC: https://www.bbc.co.uk/programmes/m000w7bq https://www.bbc.co.uk/programmes/m000w7bq From my limited personal experience and having attended various psychedelic talks and integration workshops etc., set, setting and (post) support are all really key to help turn what can be a potentially life changing/affirming/challenging event into a beneficial one.
animal531 2y ago
This is an interesting combination with this post from yesterday (Study reveals how anesthesia drug propofol induces unconsciousness): https://news.ycombinator.com/item?id=40981421 https://news.ycombinator.com/item?id=40981421 Their conclusion in that paper is that Propofol derails the brain’s normal balance between stability and excitability, which induces unconsciousness.
mdrzn 2y ago
n = 7 is really low, but interesting study. Would love to see a n = 1000 study of this.

273 points by kieckerjan 2y ago

incredibly powerful drug. we should be training a legion of mystics using psilocybin instead of criminalizing it and obfuscating the implications of its use

worik 2y ago
> training a legion of mystics Oh yeah! But what does that mean?
- RALaBarge 2y ago
  Well, we would need the mystics to figure that out for us.
  - sowut 2y ago
    it's not that complex
- wlonkly 2y ago
  It means a lot of them!
- sowut 2y ago
  it means regimented deep psychedelic experiences with focus on particular skills whether it be programming, music, art, writing, or any particular focus area. the results to be discussed, studied, understood, appreciated. almost like a college of psychedelics.
antegamisou 2y ago
You're like 70 years late https://en.wikipedia.org/wiki/MKUltra https://en.wikipedia.org/wiki/MKUltra Project MKUltra was an illegal human experiments program designed and undertaken by the U.S. Central Intelligence Agency (CIA) to develop procedures and identify drugs that could be used during interrogations to weaken people and force confessions through brainwashing and psychological torture. [...] The project studied the effects of psychoactive drugs, particularly LSD, psilocybin, mescaline, cocaine, AMT and DMT on people
- sowut 2y ago
  except that was a secret government program and humans were used as guinea pigs. that's not what i'm talking about at all

jiveturkey 2y ago

> MEQ30 Mystical Experience Questionnaire

jkingsman 2y ago
See more info here: https://psychology-tools.com/test/meq-30 https://psychology-tools.com/test/meq-30

jklinger410 2y ago

[flagged]

herodoturtle 2y ago
I read this and it instantly “clicked” - thank you for the analogy. I must ask, is this based on scientific evidence?
- haswell 2y ago
  Not the parent, but my understanding is that the effects have a lot to do with the brain entering a short term state of neuroplasticity at a level that is not normally experienced in adulthood. The result being that processing emotions and making key realizations actually “stick”. It’s possible for example as someone who suffers from PTSD to realize that it’s no longer necessary to be on high alert, but the body is anyway. I’m also no expert so take this with a grain of salt, but I think it’s less of a defragmentation and more of an increase in pliability that leads to lasting changes. This is one of the reasons that Psylocibin-assisted therapy is showing such promising results. The brain entering that state unguided may or may not lead to good results. But when a trained therapist is involved, outcomes improve.
- jkingsman 2y ago
  This study would certainly seem to indicate that this is at least true in some form — the study shows that parts of the brain that are typically very well correlated with each other (one fires then the other fires, or they fire together) come uncoupled from each other under the influence of psilocybin. I'm not sure it could be correctly stated in the gross sense as "jumbling it up and making it re-build," but there certainly is a shift in how the brain's components work together for the duration of the drug's effects, per this study.
deleted 2y ago
[deleted]
Obscurity4340 2y ago
Do you know similar stuff about dissociatives, like NMDA-antagonists? Are their effects in any way comparable or is it completely different net results?

jkingsman 2y ago

This concerns Functional Connectivity[0], which is basically a measure of how temporally correlated regions are; those that fire in sync or in a strongly correlated pattern are functionally connected. Essentially, the TL;DR of this study is that psilocybin's 5-HT2A agonism seems to reduce synchronized FC activity not just in neurons but the whole brain: psilocybin makes parts of the brain overall that otherwise work together (in a time-correlated sense) stop displaying time-correlation. These results were seen most in the Default Mode[1] network, which is more or less the brain system in operation when you are inside your head — daydreaming, thinking, remembering, etc. — as opposed to processing visual cues or observing the physical world. [0]: https://en.wikipedia.org/wiki/Dynamic_functional_connectivity https://en.wikipedia.org/wiki/Dynamic_functional_connectivit... [1]: https://en.wikipedia.org/wiki/Default_mode_network https://en.wikipedia.org/wiki/Default_mode_network — this article is one of those that just blows my mind clean out my ears (heh); the brain is such a wonder.

jppittma 2y ago
I think the fact that nobody knows how to deal with negative correlations in functional connectivity takes away from the validity of the whole concept. People literally throw out negatively correlated voxels/ROI's. This, on top of the fact that functional connectivity is only related to physical connectivity in the abstract. (it's about the correlated time series activity in pixels over time, and isn't bound by any cellular connectivity). I just struggle to discern any meaning from the concept.
- free_energy_min 2y ago
  any source that mentions throwing away negative correlations?
  - parpfish 2y ago
    It’s commonly done in fMRI studies and I always got the impression it was less about not being able to understand negative relationships (e.g., it’s well understood that things like the default mode network is inversely related to active processing) and it’s more about not being clear how to use negative values as edge weights in graph theoretic analysis of networks

trumps-ear-bug 2y ago

This can be a good thing, to reboot your brain

notnaut 2y ago

While the analogies are often useful, everyone reading HN comments should be very aware and very skeptical of just how often computer/tech people rely on computer/tech analogies to understand things that are fundamentally not computers/tech. It is very very easy for smart people with functionally specific jobs/hobbies/ways of thinking to see all reality through that narrow window. It often leads to important details being glossed over or entirely missed. The more self-confident ones quickly start seeing the analogies as fundamental facts, usually with negative consequences like loss of empathy or a tendency to see big picture generalizations as specific universal truths. Mushrooms have had a similar effect on me at times. You can start feeling like you KNOW big sweeping Truths. Similar to religiously “knowing” something. And that feeling of knowing is hard to overcome. But it is just a feeling.

codr7 2y ago
I would argue it's way more meaningful... It's unconscious knowledge; maybe not ready to hit the surface yet, but still actively affecting your life from within. Whatever glimpses you get is just what you're capable of dealing with atm. Everybody's experience is different.
- stvltvs 2y ago
  It might clarify things to say unconscious beliefs, expectations, or thought patterns instead of knowledge. It doesn't seem that the subconscious mind is a font of pure wisdom and knowledge but it powerfully affects us in ways that our conscious mind isn't aware of, by definition. Before using psychedelics, it's important to anchor ourselves by questioning the difference between knowing something and feeling like we know something.
  - mock-possum 2y ago
    One thing that a lot of people struggle with is seeing their feelings as ‘just’ feelings - it’s got to be something to do with our biology, where we instinctively seek out and cling to answers for why we feel a certain way - to justify our feelings I guess - instead of recognizing them as ‘just’ feelings, and seeing that instinct for what it is - ‘blind’ instinct that can easily seduce us into false beliefs.

philip1209 2y ago

Cool paper. I know some tech people have been donating to psilocybin research - is there any apparent connection to this study?

jdietrich 2y ago
No. https://www.nature.com/articles/s41586-024-07624-5#Ack1 https://www.nature.com/articles/s41586-024-07624-5#Ack1

TechDebtDevin 2y ago

PSA: My buddy shot himself in the head while we were on shrooms in our twenties. He thought he meant God, took a shower picked up a gun and shot himself in the head. While I've had trips since then and do get benefits from those experiences. People without experience should be careful, especially if you have a history of mental illness. He did have a history to some degree but not overtly.

JohnMakin 2y ago
[flagged]
- stvltvs 2y ago
  I think what you said is compatible with OP. It urged caution, not prohibition.
- bogota 2y ago
  You don’t need to be a doctor or therapist to let people know that some people can have very bad reactions and it’s not all roses. I see the same thing happening in people smoke marijuana where any claim that it can have harmful effects for some or with abuse is met with “yeah well what do you know, i read this other thing and i never had issues myself”.
  - JohnMakin 2y ago
    It seems to me that in this case the issue was someone out of their mind high on shrooms had immediate access to a gun, not the “mentally ill person does drugs and dies” trope which is quite tired and I’m pretty sure not backed by any kind of science. I only posted my reply because comments like these add to the stigma of mental illness and may make people who are suffering less willing to try these types of treatments.
    - darkerside 2y ago
      This observation of fact is more interesting and nuanced than your initial defensive reaction

lawlessone 2y ago

>Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6–12 months later. Not simultaneously I hope.. that sounds like it would be a rough ride

jkingsman 2y ago
No, they were separate dosages to compare FC effects.
titanomachy 2y ago
"[methylphenidate] was selected as the active control condition to simulate the cardiovascular effects and physiological arousal (that is, controlling for dopaminergic effects) associated with psylocybin"
brotchie 2y ago
"it can generally be assumed that there is approximately 15 mg (+/- 5 mg) of psilocybin per gram of dried mushroom" -Wikipedia So 25mg is ~1.5g of dried mushrooms. Decent dose, but not a "omg I'm one with the universe." For instance, a "Hero Dose" typically starts at 5g of dried mushrooms, so ~3x the dosage used in the study. Though it's possible the uptake rate using their dosing mechanism is much higher than "stomach acid digested dried mushrooms."
- mistrial9 2y ago
  some kinds of mushrooms can grow tolerance fairly quickly, also.. based on info from a friend
- newzisforsukas 2y ago
  > So 25mg is ~1.5g of dried mushrooms. 1.25g - 2.5g *
  - collyw 2y ago
    That isn't a high dose. Medium.

poikroequ 2y ago

Reading this feels an awful lot like watching the video about the retro encabulator.

empath75 2y ago

I can't think of anything in the world I would enjoy doing less than completing "a simple auditory–visual matching task" while in an MRI scanner on shrooms.

kjkjadksj 2y ago
The set and settings researchers typically use for usual psych studies are going to bias psychedelic results so much. Think that building you hated in undergrad's crusty unlit cinderblock basement with no windows but coated in cameras and microphones. Its so dystopian, you are literally a caged rat. I don't think you can perform this research in good faith without having experienced a proper trip yourself. It's just impossible to put into words much less gleam any actual understanding from written description of it. Science needs more Albert Hoffman's who are willing to couple their knowledge with this experience without fear of being fired from IRB violation and ostracized by the scientific community. Otherwise we will forever be grasping in the dark with these drugs.
- titanomachy 2y ago
  gleam -> glean
  - kjkjadksj 2y ago
    Too late to edit :(
- dylan604 2y ago
  I would suggest the world needs more Shulgins as well. https://en.wikipedia.org/wiki/Alexander_Shulgin https://en.wikipedia.org/wiki/Alexander_Shulgin
- gorlilla 2y ago
  I've never had a good trip indoors. My brain has a knack for staying grounded by familiar settings, so I hardly even experience the trip. Put me outdoors in the dark and my brain can be stimulated by natural sounds which are not nearly as predictable as those I find indoors. I think it has to do with processing stimuli that I can't instantly attribute to something I know very well. I am also normally hypervigilant, which may come into play since I think familiar settings inhibit my ability to fall under the effects of intoxication somewhat. I am also much more likely to try and sleep off any overwhelming feelings if I'm in the aafety/comfort of a house vs the middle of the forest. Setting doesn't necessarily mean the 'safest' space for you since my own home negatively effects the overall experience. Having someone who is experienced, sober and willing to guide you for hours (lots of trust) is crucial since the opti.al setting may not be the safest setting. TL;DR - I struggle to trip or even enjoy a trip indoors. I have always felt shrooms work best when you let them help you attune to nature. Listening to the wind, trees, insects, etc... it's like washing your eyeballs with kittens.

Unbefleckt 2y ago

While it's amusing in the short term, the long term side effects for me were awful. I felt like my brain was slow and unfocused, I was no longer quick in conversation or able to concentrate as well as usual, I felt disconnected from myself, sort of like when you recall a memory so old that it seems like it belongs to someone else, I had a headache for almost 3 weeks. Throwing this in here as there are a fair few "dude just take drugs" comments and worry they might be the religious types.

cthalupa 2y ago
That's interesting, because I don't that anyone really has reported these side effects and I don't believe there are any known pharmacological effects from psilocybin or psilocin that would cause any of that. Were they dried mushrooms you ate? Do you trust the provenance of them? If they were a chocolate bar or similar, many of those do not actually have psilocybin or psilocin in them, and are instead using a variety of different research chemicals that are significantly less understood. If it was dried mushrooms, there are a variety of species that induce hallucinogenic effects through other chemicals than what you find in your usual magic mushrooms. They might have been regular shrooms, of course - people react to things differently - but that's a different enough outcome that I wonder if it wasn't something else entirely.
- newzisforsukas 2y ago
  > I don't believe there are any known pharmacological effects from psilocybin or psilocin that would cause any of that What are your qualifications to make a claim like that? There hasn't been much clinical research in humans using psilocybin until very recently [1], and they certainly do not cover the range of different species of mushrooms that contain the alkaloids [2]. 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016263/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016263/ 2. https://en.wikipedia.org/wiki/List_of_psilocybin_mushroom_species https://en.wikipedia.org/wiki/List_of_psilocybin_mushroom_sp...
  - cthalupa 2y ago
    My qualifications for saying "I don't believe there are any known effects that match that" is... reading quite a lot of clinical research on their usage, and not having seen anything that would match those effects. You'll notice I qualified that statement in two ways - both that it is limited to my personal understanding and that of 'known' effects. I'm not really sure what you're arguing - neither of these links indicate otherwise. Are you familiar with the null hypothesis? Unless we have evidence of something being the case, why would we think it would be the case? We also have decades of anecdotal reports on usage of psilocybin and psilocin containing mushrooms and I'm also not aware of any significant evidence from that that such an effect is even remotely common - it's the first I've ever encountered that sort of story about persistent headaches for multiple weeks following their usage.

deleted 2y ago

[deleted]

trallnag 2y ago

LSD is better, sorry :/

GuB-42 2y ago
Psilocybin and LSD are both psychedelics and 5-HT2A agonists. Even though the study uses psilocybin, the findings should apply to LSD too.
- xk_id 2y ago
  Not really. Two ligands of the same receptor can have very different effects. There are 5ht2a agonists who don’t even cause perceptual effects. Besides, LSD has activities at several other receptors as well, which contributes to its effect. Extrapolation of biological effect based on the receptor affinity of a ligand is a pretty crude hypotheses.
  - GuB-42 2y ago
    I am not inventing this, it is what the study itself suggests. > To determine whether this reflects a common effect of psilocybin that generalizes across datasets and psychedelics, we calculated dimension 1 scores for extant datasets from participants receiving intravenous (i.v.) psilocybin55 and lysergic acid diethylamide (LSD)56. Psychedelic treatment increased dimension 1 in nearly every participant in the psilocybin and LSD datasets (Fig. 2c), suggesting that this is a common effect across psychedelic drugs and individuals.
kinakomochidayo 2y ago
Probably depends on your objective. Mushrooms are much gentler and forgiving than LSD when it comes to traumas.

mike_ivanov 2y ago

It's interesting that brain hypersynchronicity is a known source of epileptic seizures (among other things). This potentially could be a treatment for this specific problem. See e.g. * https://www.sciencedirect.com/science/article/pii/S089662731930964X * https://onlinelibrary.wiley.com/doi/full/10.1111/j.1528-1167.2010.02805.x

greentxt 2y ago
Doubtful. Shrooms cause seizures.
- CacheRules 2y ago
  Sources?
  - __MatrixMan__ 2y ago
    Anecdotal, but I've tripped with two people who showed seizure like symptoms that they never had before or since. Couldn't find any data at the time. Tried to get them to submit experience reports on erowid so that there would be some data out there, but they didn't want to put anything about it in writing.
    - mistrial9 2y ago
      ok - an underweight 20 year old woman who did not eat well before a Rolling Stones concert and then used cocaine and alcohol, also had a seizure. goddam Mick Jagger !
    - foobiekr 2y ago
      Are you sure shrooms? If chocolates or gummies the compound therein is not quite the same as recent news stories have noted.
      - __MatrixMan__ 2y ago
        Yeah, I grew them. I didn't sequence them for identification, but they were phenotypically P. Cubensis, as advertised on the spore syringe. In neither case was it a big deal in the long run (not exactly great vibes in the short term though). I used to be a pretty enthusiastic user, so "just two times" is indeed uncommon. Hopefully with the recent trend of decriminalization we can get together some respected data about this sort of thing. I still believe that psilocybin has been a net positive thing for most people who have tried it (including these two cases). Even if the seizure thing were confirmed, all the conventional wisdom re: tripping remains unchanged. Be in a safe place with trusted people, consider a trip sitter, etc. On the other hand, I think having the data might help drive some better decisions: Situations you might avoid (e.g. swimming), etc.

motohagiography 2y ago

Feedback in an anlog signalling system producing delays, reflections, geometric and clipped artifacts is something anyone who has used a guitar effects pedal is familiar with. I have a surprising number of old comments on this site about how hallucinogens just impair signalling and the results are geometric for the same reasons. This article says it impairs the equivalent to the CLK signal, which sounds just about right. Don't be disappointed about it not being another spiritual dimension, they discovered we literally have effects pedals for our brains. This is the coolest thing ever. We could probably classify hallucinogenic artifacts by chorus, delay, flange, harmonics...

l33tbro 2y ago
The problem is getting so out of it that you can't reach the wet/dry knob to dial back the wacko.
cmehdy 2y ago
Paychonautwiki has been classifying effects in a somewhat similar fashion for years/decades now: https://psychonautwiki.org/wiki/Geometry https://psychonautwiki.org/wiki/Geometry

RamblingCTO 2y ago

Lots of people have a lot of negative stuff to say, but my take is: if you do psychedelics, you need to do the work and you need a firm ground before that. We have research that it might help with PTSD, depression, etc. but it's not like you just take it and you're done. It's a powerful substance and with power comes responsibility. I like to think of it more as an enhancer as to what's inside your head anyways. If that's fucked already, how are psychedelics gonna help you?

zild3d 2y ago
> We have research that it might help with PTSD, depression, etc. but it's not like you just take it and you're done. Worth noting the research is on psilocybin with supportive psychotherapy, not just take some mushrooms you got from a guy and have at it. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2020/11/psychedelic-treatment-with-psilocybin-relieves-major-depression-study-shows https://www.hopkinsmedicine.org/news/newsroom/news-releases/...
- RamblingCTO 2y ago
  Exactly what I was thinking about! There are some nice studies being done in Switzerland with a trip + 7 (I believe) sessions before and after
- kazinator 2y ago
  So, take some mushrooms from a guy, lie down on the couch, and tell him about your mother.
- Litost 2y ago
  There's a good documentary about the John Hopkins research on treating drug resistant depression with psilocybin which unfortunately isn't available any more via the BBC: https://www.bbc.co.uk/programmes/m000w7bq https://www.bbc.co.uk/programmes/m000w7bq From my limited personal experience and having attended various psychedelic talks and integration workshops etc., set, setting and (post) support are all really key to help turn what can be a potentially life changing/affirming/challenging event into a beneficial one.

animal531 2y ago

This is an interesting combination with this post from yesterday (Study reveals how anesthesia drug propofol induces unconsciousness): https://news.ycombinator.com/item?id=40981421 https://news.ycombinator.com/item?id=40981421 Their conclusion in that paper is that Propofol derails the brain’s normal balance between stability and excitability, which induces unconsciousness.

mdrzn 2y ago

n = 7 is really low, but interesting study. Would love to see a n = 1000 study of this.