[HN Gopher] Psilocybin desynchronizes the human brain
       ___________________________________________________________________
        
       Psilocybin desynchronizes the human brain
        
       Author : kieckerjan
       Score  : 140 points
       Date   : 2024-07-17 16:10 UTC (6 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | sowut wrote:
       | incredibly powerful drug. we should be training a legion of
       | mystics using psilocybin instead of criminalizing it and
       | obfuscating the implications of its use
        
       | jiveturkey wrote:
       | > MEQ30 Mystical Experience Questionnaire
        
         | jkingsman wrote:
         | See more info here: https://psychology-tools.com/test/meq-30
        
       | jkingsman wrote:
       | 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_connectivit...
       | 
       | [1]: 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 wrote:
         | 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 wrote:
           | any source that mentions throwing away negative correlations?
        
           | robwwilliams wrote:
           | I second the question below. The phase, magnitude, and
           | polarity are all used. Yes, sure, you can focus on sub-
           | systems with positive correlation under the presumption that
           | joint increases in signal signify joint increases in O2 use
           | and neuronal activity. Functional connectivity is functional
           | more relevant than mere axonal connectivity. Only a small
           | fraction of an axonal arbor -- its collection of presynaptic
           | terminals---is functionally and reliably coupled to
           | postsynaptic targets.
        
         | nikkwong wrote:
         | Yeah, this is super interesting. The obvious follow up for me
         | is what implication this desynchronization has on cognition.
         | People who have done a lot of psilocybin tend to be quite a bit
         | 'different' at least in my experience--they tend to be more
         | reserved, maybe a bit more thoughtful, slower, introspective,
         | etc.
         | 
         | But what causes this change in personality? People who have
         | done a lot of psilocybin seem to be a lot less worried, a lot
         | less neurotic, and a lot less wrapped up in the ego than those
         | who haven't. After all, who wants to be wrapped up and
         | ruminating based on the content of their thoughts? I've always
         | thought of this behavior by those who have used psilocybin to
         | be a feature, not a bug--as if they're enlightened.
         | 
         | But if, say, this newfound personality is the result of a loss
         | in functional connectivity--what does that tell us about how
         | other markers of cognitive function have changed? Is strong FC
         | a prerequisite for strong executive function or other measures
         | of intelligence? The paper seems to suggest that the changes in
         | FC are associated with the default mode network and maybe not
         | other states of brain focus.
         | 
         | But will a macro dose of psilocybin, say--make someone better
         | at their job? Maybe we don't know yet, and maybe there won't be
         | a clear answer; there is a lot of heterogeneity in the way
         | people think, and how they exploit their own cognitive
         | abilities to provide value in the world--so maybe a loss in FC
         | will mean different things to different individauls. But given
         | the suggestion from this paper that the effects of psilocybin
         | may be somewhat permanent, the answer to this question will be
         | a very useful for those looking to benefit from this
         | therapeutic.
        
           | robwwilliams wrote:
           | The study uses cool methods but they are still at very crude
           | global level and the temporal resolution is poor. Functional
           | synchrony (or para-synchrony) is more of an initial pointer
           | to the much faster synaptic processing we really would love
           | to understand better. the ither limit is that fMRI studies
           | focus on relatively large chunks of cortex, but lots of
           | critical changes are sub-cortical. I'd love to see a focus on
           | thalamo-cortico and cortico-thalamic modulation. I suspect
           | these connections are just as important as cortico-cortical
           | and cortico-hippocampal connections.
           | 
           | Finally, there will be a great deal of individual
           | differences. One story will not fit all of us.
        
       | trumps-ear-bug wrote:
       | This can be a good thing, to reboot your brain
        
       | notnaut wrote:
       | 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 wrote:
         | 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 wrote:
           | 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 wrote:
             | 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.
        
               | codr7 wrote:
               | Yeah, feelings are real.
               | 
               | Though most of them probably have very little to do with
               | you.
        
         | throwaway_82467 wrote:
         | I'm convinced this is actually a symptom of using psychedelics.
         | 
         | Ironically, using quite a lot of anec-data, there definitely
         | seems to be a correlation between use of psychedelics among
         | myself/peers and how "suggestible" people are. I've seen a lot
         | of folks go really deep in conspiracy theories (regardless of
         | the political/social positioning), strong religious beliefs, or
         | similar such lines-of-thought that require a "leap of faith" or
         | reasoning-by-analogy. Overall I believe that something about
         | taking them puts you into a state of mind that is more "open",
         | and therefore, more "gullible" to believe that you are latching
         | onto some profound truth or significant idea.
        
           | bubblyworld wrote:
           | I've never been sure which way the causation goes (if any),
           | but I've known three people so far who had psychotic breaks
           | after an intense mushroom trip. Similar to what you wrote - a
           | sudden obsession with conspiracy theories and/or intense
           | religious persuasions. Something they all had in common was
           | being very confident and self-assured to begin with, which
           | makes me wonder if it's particularly risky for those kinds of
           | people? They all recovered, fortunately.
        
           | ajb wrote:
           | Your theory reminds me of this (long) article:
           | https://slatestarcodex.com/2016/09/12/its-bayes-all-the-
           | way-...
        
         | bubblyworld wrote:
         | I've had similar experiences on mushrooms (and high doses of
         | marijuana too, to a lesser extent). It feels like a mix of
         | intense awe and the the satisfactory "click" of finally
         | understanding something to me. I'm quite sure it's more of an
         | emotional state than "fundamental truth", or anything like
         | that, but it sure is powerful.
         | 
         | Very easy to understand how mythology can build around the
         | stuff.
        
           | sdwr wrote:
           | Mythology, also procedure.
           | 
           | If I am a member of a tribe that uses ceremonial ayhuasca at
           | regular intervals, I will build my relationships around that
           | cycle, so the feeling of awe and understanding corresponds
           | with an actual personal breakthrough or meaningful group
           | event. That's the 10x use case
        
             | bubblyworld wrote:
             | That's an interesting idea, thanks. I might consider trying
             | it!
        
             | jdietrich wrote:
             | _> That's the 10x use case_
             | 
             | It might be, or it might be a ritual that has no meaningful
             | benefit. There's a huge amount of hype around psychedelics,
             | but extremely limited evidence with a very high risk of
             | bias.
        
           | Apocryphon wrote:
           | > It feels like a mix of intense awe and the the satisfactory
           | "click" of finally understanding something to me.
           | 
           | I almost wonder if all of this is simply because drugs can
           | produce a strong anti-anxiety / euphoric effect, providing a
           | powerful sense of confidence in one's convictions.
        
             | progmetaldev wrote:
             | As well as the complete opposite effect for certain
             | individuals, which I think is just as important to study to
             | help those that have these reactions. I can imagine the
             | mythology built around visions of Hell/negative afterlife
             | could have just as easily been sparked by negative
             | psychedelic experiences.
        
             | superturkey650 wrote:
             | It also seems to remove my ability to contextualize things
             | which means I can't find flaws in my understanding of
             | something as easily. This works for both good/euphoric
             | things, where I feel like I know something (but really I
             | can't find the flaws in my reasoning), and for bad/anxiety
             | things, where I can feel really bad and spiral on something
             | because I get focused on one particularly bad aspect and
             | can't see the full picture.
             | 
             | I feel like this is why drugs can sometimes help with
             | creative things, especially if you're familiar with the
             | drug, as long as you can harness this decontextualization
             | to put more of your focus on one thing, kind of like
             | clearing your mind. However, its usually fruitless/harmful
             | in anything requiring complex reasoning/judgement because
             | it is reducing your ability to see the big picture.
        
         | itronitron wrote:
         | Feeling "it is just a feeling" is also just a feeling.
        
           | notnaut wrote:
           | Not in the sense I meant. The "enlightenment" confidence and
           | awe-struck assuredness is the feeling and it comes from deep
           | inside.
           | 
           | Recognizing that confidence and assuredness are not knowledge
           | is not quite the same as those feelings themselves. Though I
           | do recognize this is sort of recursive and cyclical and
           | ultimately there's nothing but some type of faith to build
           | everything on, including doubt/skepticism.
        
           | baq wrote:
           | Absolutely not.
           | 
           | Feeling "it is just a feeling" is being grounded in reality
           | and affirming your senses and convictions are volatile and
           | shouldn't be trusted.
           | 
           | Feeling "I solved the world, everybody listen to me" is...
           | not.
        
           | snapcaster wrote:
           | Not really, have you ever tried to articulate one of your
           | "big epiphanies" while on hallucinogens? In my experience
           | (and experience of people I'm with) it inevitably comes out
           | as babble. Maybe that's just because the insight is too
           | profound to capture with language but somehow I doubt it
        
           | TaylorAlexander wrote:
           | Actually we overload the word "feeling" to include thoughts
           | and perceptions which are not feelings. Like "I feel sad" is
           | a feeling. "I feel like you are being a jerk" is not a
           | feeling it is a thought or perception.
        
         | uoaei wrote:
         | There are ways things can be computers that don't require the
         | typical setup of a von Neumann architecture. Psilocybin taught
         | me that. My education and subsequent studies confirmed that.
        
         | 01HNNWZ0MV43FF wrote:
         | > You can start feeling like you KNOW big sweeping Truths.
         | 
         | Yep. During a pretty bad episode of delusional schizophrenia
         | (for lack of any better diagnosis) I had that, many years ago.
         | 
         | I felt like I was either on the verge of a huge epiphany or I'd
         | just had one, for a few weeks. Every time it was nonsense or
         | couldn't be explained.
         | 
         | Luckily I have not relapsed and I have been off the
         | antipsychotics for a few years
         | 
         | The only permanent damage is that every medical professional
         | says I should never do psychoactive drugs. Which sucks cause
         | they sound fun and I wonder if they'd help me get over some
         | other problems I have. Maybe after I've retired.
        
         | DaoVeles wrote:
         | My favorite shrooms story is from reddit.
         | 
         | Someone when taking schrooms would always "talk to God" and
         | would get answers but they could never remember them the next
         | day. So one day they ensured they had a notepad around to write
         | down the answers.
         | 
         | They did the trip and asked "What is the meaning of life?".
         | When they woke up all that was written on the note pad was
         | "walls".
         | 
         | It must have felt profound at the time but it was basically
         | meaningless. And that is a lot of drugs.
        
       | philip1209 wrote:
       | Cool paper.
       | 
       | I know some tech people have been donating to psilocybin research
       | - is there any apparent connection to this study?
        
         | jdietrich wrote:
         | No.
         | 
         | https://www.nature.com/articles/s41586-024-07624-5#Ack1
        
       | TechDebtDevin wrote:
       | 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.
        
         | TaylorAlexander wrote:
         | Thanks for sharing. Not sure if the guidance to do shrooms in
         | an appropriate setting and with an appropriate mindset ("set
         | and setting") would have helped, but certainly that guidance is
         | no joke!
         | 
         | And we should absolutely continue research to learn more about
         | the adverse effects. Obviously they help a lot of people, but
         | must be done with care and seem not to be helpful for every
         | person. We must learn more about these conditions.
        
         | ddingus wrote:
         | Thanks for that PSA. And here's to your lost friend!
         | 
         | I have a lost one too, but due to a different cause. He took
         | hard drugs he was dealing to pay off a house after a
         | legislative decision basically eliminated his well paying job.
         | We grew up very much do what it fucking takes kind of people.
         | And we were tested in life more than once. I still draw from
         | that time today, sometimes remembering and finding that which
         | will get me through. I miss him terribly.
         | 
         | Had he not used, he would have made it! We talked about that,
         | and he used "a little" to know better what he was dealing. Now
         | we all make choices and he made his. At the time, financially,
         | it was understandable, though I would have chosen differently
         | myself.
         | 
         | Anyhow... hard lessons!
         | 
         | Lost him in my very early 30's and I think of him regularly, as
         | I am sure you do yours. What got him was the loss of autonomous
         | breathing! Yes, right out of Greek mythos, he suddenly had to
         | breathe consciously after a particularly nasty interaction with
         | some of the product and his physiology.
         | 
         | It truly was a curse. Bit by bit, he lost the fight. Was cruel
         | and hard to watch.
         | 
         | Sidebar: I am angered and lament the timing because I very
         | strongly feel some form of electrical stimulation could have
         | helped. I lacked means at the time. We both really wanted to
         | try. Doctors had nothing.
         | 
         | End sidebar.
         | 
         | These drugs have awesome potential, but they also come with
         | considerably greater risks than many of us know too.
         | 
         | Good PSA. Seconded.
         | 
         | Be careful peeps. We think we understand. Fact is we just don't
         | yet.
         | 
         | And that will improve with proper study using the scientific
         | method.
         | 
         | If you ask me, cutting those risks is the single most powerful
         | argument for permitting ongoing research and study of the
         | powerful things left for us in Mother Natures kitchen.
        
           | voisin wrote:
           | > And that will improve with proper study using the
           | scientific method.
           | 
           | How about just having supervised sites with trained trip
           | sitters so that people don't have the ability (under the
           | influence) to do irreversible things? Perhaps in a
           | therapist's/doctor's office.
        
             | ddingus wrote:
             | Did you read what I shared?
             | 
             | Yes, that would be better than a free for all. Of course.
             | 
             | The guy I lost had unique physiology that meant he was
             | unable to use a substance most can with far fewer worries.
             | 
             | We have that data point now, and I hope it made it into the
             | literature too.
             | 
             | But getting it was expensive! Cost one good person, and
             | left a family without a father and many other souls, myself
             | included, hurting.
             | 
             | More is needed.
             | 
             | And I am not saying your suggestion is bad. I sure do not
             | see it that way.
             | 
             | It is just inadequate in light of the real problem space,
             | that's all.
             | 
             | And remember, just taking it IS an irreversible thing. For
             | most, that is not a big deal.
             | 
             | For some, it is a HUGE deal and the hard fact is we do not
             | understand who is who in all that.
             | 
             | Peace, live well, play safe.
        
           | defgeneric wrote:
           | Why didn't they use a respirator?
        
             | ddingus wrote:
             | They did. But things slip, machines fail, etc.. it is quite
             | insidious.
        
         | kjkjadksj wrote:
         | Part of the lesson of this story is the danger of having a gun
         | in the home at all. He could have been sober and depressed and
         | did the same just as easily thanks to having access to a gun.
         | There's a lot of statistical evidence for how dangerous
         | situations like depression or domestic violence can become once
         | a gun is nearby.
        
           | psunavy03 wrote:
           | Your first statement is not supported by the second. Yes, in
           | a DV situation or a situation where someone has severe mental
           | illness, it's probably not a good idea to have easy access to
           | a firearm.
           | 
           | But if you actually look at the numbers, the average firearm
           | is not used in self-defense, nor is it used to endanger a
           | family member. The vast majority just . . . sit there.
           | They're machines which must be used respectfully and
           | responsibly, not magic evil talismans.
        
             | johnmaguire wrote:
             | > The vast majority just . . . sit there.
             | 
             | This is irrelevant to the statement that having a gun
             | around is more dangerous than not having a gun around.
             | 
             | https://med.stanford.edu/news/all-news/2020/06/handgun-
             | owner...
             | 
             | https://med.stanford.edu/news/all-news/2022/04/handguns-
             | homi...
        
             | 613style wrote:
             | Yet it remains true that not having magic evil talismans in
             | my house makes it very unlikely that my family or I get
             | cursed by accident.
        
             | jrussino wrote:
             | > if you actually look at the numbers, the average firearm
             | is not used in self-defense
             | 
             | Those aren't really the numbers you'd want to look at,
             | right? If you have a community with 1000 firearms and 499
             | of them end up being used in a shooting you could still
             | assert that "most firearms are never used".
             | 
             | I think what you'd care about in assessing risk is: what is
             | the likelihood of violent injury and/or death in household
             | with firearms vs households without? Controlled for other
             | relevant factors?
             | 
             | I've never seen this particular assessment presented in the
             | way I've described it, but then again it sounds like there
             | are some political hurdles to studying gun violence:
             | https://abcnews.go.com/US/federal-government-study-gun-
             | viole...
        
             | luluthefirst wrote:
             | Most landmines also just sit there.
        
         | jeremiahbuckley wrote:
         | A user named observationist made a response to this post, but
         | they responded to a troll, whose comment was nuked which
         | removed their very valuable comment (I was responding to them
         | at the time so I happened to have both in cache).
         | 
         | observationist
         | https://news.ycombinator.com/user?id=observationist original
         | comment:
         | 
         | Around 1% of people have schizophrenia. This holds over a
         | lifetime - there's a structural, unavoidable component to the
         | person's neural wiring or physiology that will result in a
         | schizophrenic break. Prior to the break, they may seem more or
         | less normal, but after, they will experience deficits in
         | cognition and perception, and may have significant barriers to
         | living a normal life. Schizophrenics, as a rule, will have a
         | psychotic break before they turn 45. Psychoactive substances,
         | and high doses of psychedelics, will trigger breaks from
         | reality earlier than they might otherwise happen. Stress,
         | caffeine, trauma, or significant excitement can also be
         | triggers, but psychedelic drug trips are a reliable trigger,
         | and in conjunction with other effects, can spiral a "bad trip"
         | into a much worse trauma.
         | 
         | Another 3 to 4% of the population have significant mental
         | disorders, ranging from those we know, to those we can observe
         | but don't have a good diagnostic criteria for. In these cases,
         | it can be very detrimental to use psychoactive substances
         | generally, and psychedelics in particular.
         | 
         | It's crucial to visit with a doctor to rule out the likelihood
         | that you're in the roughly one in twenty people that might have
         | a significant negative reaction to psychedelics. Some of the
         | people in that camp might be safe from harm later in life. I
         | know a person with significant family history of schizophrenia
         | and earlier life indicators he was at risk, who then started
         | using mushrooms in his 50s and seems very stable. He talked
         | things over with his doctors before deciding to take the risk -
         | apparently after you turn 45 it's incredibly rare, even with
         | significant trauma and stressors, for schizophrenic breaks to
         | occur, so if that's your main threat, it might be safe to
         | engage in psychedelics when you're older.
         | 
         | If you're not in the high risk camp, you should still have at
         | least one frank discussion with your doctor about pitfalls, and
         | do a metric ton of personal research about any substance you
         | intend to use. It can be a profound and wonderful departure
         | from the norm, or a mildly unpleasant experience, or a
         | stressful confrontation with your inner demons, depending on
         | the dose and preparation.
         | 
         | my response:
         | 
         | Thank you for this. I thought this was a very informative
         | comment; I am worried about schizophrenia as a disease that
         | might impact my kids. I wanted to ask you for more information,
         | but that is a burden, so I asked ChatGPT instead so at least
         | you wouldn't have to go find links. If you have Other reading
         | besides what is below I would be happy to hear about it.
         | 
         | Here is it's response from ChatGPT (Claude couldn't provide
         | links). My contribution is that I checked the links and skimmed
         | them to see if they supported the statement. They are
         | repetitive (there are only 7 articles linked actually), but
         | they generally support your comment. Of note the PLOS article
         | does not support your comment, and it seems that it doesn't
         | support what ChatGPT says (maybe I misunderstood when skimming
         | it). The stuff in parens below (Looks Like This), was a link in
         | ChatGPT, but the links didn't copy-paste, so I'm going to put
         | all the articles at the top here:
         | 
         | https://www.nature.com/articles/s41380-023-02138-4
         | 
         | https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12...
         | 
         | https://www.who.int/news-room/fact-sheets/detail/schizophren...
         | 
         | https://www.nimh.nih.gov/health/statistics/schizophrenia
         | 
         | https://www.psychiatrictimes.com/view/drug-psychosis-may-pul...
         | 
         | https://psychedelics.berkeley.edu/qa/understanding-your-risk...
         | 
         | https://journals.plos.org/plosone/article?id=10.1371/journal...
         | 
         | The comment you saw online contains some accurate points but
         | also could benefit from additional context and nuance based on
         | available research.
         | 
         | 1. Prevalence and Risk Factors of Schizophrenia:
         | 
         | - The lifetime prevalence of schizophrenia is approximately
         | 0.3% to 0.7% globally, which supports the 1% figure as an upper
         | bound (Nature) (BioMed Central) (World Health Organization
         | (WHO)) .
         | 
         | - Schizophrenia typically emerges in late adolescence to early
         | thirties, with men often experiencing onset earlier than women
         | (National Institute of Mental Health) (World Health
         | Organization (WHO)) .
         | 
         | - Factors such as genetic predisposition, prenatal exposures,
         | and psychosocial stressors contribute to the risk of developing
         | schizophrenia (National Institute of Mental Health) (World
         | Health Organization (WHO)) .
         | 
         | 2. Triggers for Psychotic Breaks:
         | 
         | - The statement that high doses of psychedelics can trigger
         | psychotic breaks in predisposed individuals is supported by
         | evidence. Drug-induced psychosis, particularly from
         | hallucinogens and cannabis, can lead to schizophrenia in some
         | cases (Psychiatric Times) .
         | 
         | - Other triggers include stress, trauma, and significant life
         | changes, which can exacerbate underlying vulnerabilities
         | (Berkeley Psychedelics) .
         | 
         | 3. Impact of Psychedelics on Mental Health:
         | 
         | - Psychedelics can pose significant risks for individuals with
         | a family history of schizophrenia or other major mental health
         | disorders. It is crucial for these individuals to consult
         | healthcare professionals before considering psychedelic use
         | (Berkeley Psychedelics) .
         | 
         | - Research has shown that about 25% of those with substance-
         | induced psychosis may transition to schizophrenia, with the
         | type of substance being a significant predictor of this
         | transition (Psychiatric Times) .
         | 
         | 4. General Mental Health Considerations:
         | 
         | - Around 3-4% of the population may experience significant
         | mental disorders other than schizophrenia. For these
         | individuals, the use of psychoactive substances, including
         | psychedelics, can be particularly detrimental (PLOS) . [NOTE:
         | This seems to be an error from ChatGPT, this PLOS article
         | doesn't seem to support this conclusion. As I haven't done
         | personal work on this yet, I don't know whether the statement
         | is supported by other research.]
         | 
         | - Mental health evaluation and professional consultation are
         | recommended before the use of psychedelics to identify
         | potential risks and ensure safety (Berkeley Psychedelics) .
         | 
         | 5. Later-Life Considerations:
         | 
         | - The risk of new-onset schizophrenia after the age of 45 is
         | indeed rare, which suggests that older individuals may have a
         | lower risk of experiencing a first psychotic episode triggered
         | by psychedelics (Berkeley Psychedelics) .
         | 
         | For further reading and to deepen your understanding, you may
         | refer to sources like the National Institute of Mental Health
         | (NIMH), the World Health Organization (WHO), and recent
         | research studies on the global burden and risk factors of
         | schizophrenia (National Institute of Mental Health) (World
         | Health Organization (WHO)) (Nature) . Additionally, the
         | Berkeley Center for the Science of Psychedelics (BCSP) provides
         | detailed information on the safety and risks associated with
         | psychedelic use (Berkeley Psychedelics) .
        
         | core_dumped wrote:
         | Similar thing. My good friend and early college roommate took
         | his own life with a gun after having a bad trip. I wasn't there
         | for it, but the way he described it he felt ridiculed and
         | deserted by his old high school friends during the trip. He was
         | left alone to deal with these feelings.
         | 
         | His mood post trip became increasingly abysmal. He became
         | highly paranoid, and started questioning the loyalty of the
         | people close to him like his family. I now know that this was a
         | sign of possible schizophrenia. I now know that dementia runs
         | in his family. He started creating simplistic yet disturbing
         | paintings. I wish I still had them.
         | 
         | This happened in March of 2020, COVID had just become a
         | national concern. I was dating long distance at the time and
         | she wanted me to come up before the airports closed down.
         | Sometimes I regret going. I wish he had gone somewhere so he
         | wasn't alone. He ended up shooting himself with his
         | grandfathers rifle.
         | 
         | I guess the lesson here is be cautious with drugs that can
         | accelerate mental illnesses if you have a family history of
         | them. Check up on your friends that have bad trips and seem
         | kinda off.
        
         | INTPenis wrote:
         | Everyone who has tripped hard and come out unscathed can
         | consider themselves lucky to have such a strong constitution. I
         | am a firm believer in that psychdelics are wonderful, but
         | powerful. And not everyone can handle the experience. At one
         | end might be a slightly anxious trip, but at the other end is a
         | complete breakdown of your reality.
        
       | lawlessone wrote:
       | >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 wrote:
         | No, they were separate dosages to compare FC effects.
        
         | titanomachy wrote:
         | "[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 wrote:
         | "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 wrote:
           | some kinds of mushrooms can grow tolerance fairly quickly,
           | also.. based on info from a friend
        
       | poikroequ wrote:
       | Reading this feels an awful lot like watching the video about the
       | retro encabulator.
        
       | empath75 wrote:
       | 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 wrote:
         | 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 wrote:
           | gleam -> glean
        
         | progmetaldev wrote:
         | I agree, they can already be mentally uncomfortable if you
         | don't like enclosed spaces. Perhaps there's some kind of
         | psychotherapeutic techniques used prior to getting in the MRI
         | during the come up period, to kind of boost positive emotion
         | about the whole process.
        
         | lucidrains wrote:
         | Indeed, the best setting is in nature on a beautiful day
        
       | Unbefleckt wrote:
       | 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 wrote:
         | 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.
        
         | loa_in_ wrote:
         | Mushrooms are very contradictory in their nature to the modern
         | "cog in the machine" lifestyle. It's a bit like being subjected
         | to a software fuzzer. I imagine if learning from one's inputs,
         | one will be afterwards less sure of concepts one was very sure
         | about, but also less sure about concepts thought previously to
         | be impossible. That will surely increase cognitive load,
         | especially when one's life is pretty straightforward.
        
           | brotchie wrote:
           | Agreed.
           | 
           | Before a controlled high dose Psilocybin experience I "felt"
           | my emotions: Anger, Fear, Frustration.
           | 
           | Afterwards, I gained the ability to observe and "catch" my
           | emotions in-flight. Not sure if it was neuroplasticity
           | induced by the substance, or "you don't know what your brain
           | can do until you know it".
           | 
           | I liken it to previously having Ring 1 access to my thoughts,
           | now I have Ring 0 access.
           | 
           | Definitely persistent: DRAMATIC improvement in my happiness
           | and wellbeing.
           | 
           | YMMV
        
         | briankelly wrote:
         | Sounds like it could be mild dissociation/depersonalization.
         | It's not typically considered a primary effect of psilocybin,
         | but there is a small mention here on classical psychedelics:
         | https://en.wikipedia.org/wiki/Dissociative
        
           | progmetaldev wrote:
           | I was already predisposed to anxiety, but after using LSD
           | quite a bit in my teens, my anxiety took over my waking life.
           | During high anxiety and panic attacks, I often experience
           | dissociation/depersonalization effects. I feel like I am
           | disconnected from myself, and watching what is happening,
           | like in a dream. The only thing I really connect with is the
           | anxiety and fear. Over the years, through therapy and
           | medication, this has become rarer.
        
       | trallnag wrote:
       | LSD is better, sorry :/
        
         | GuB-42 wrote:
         | 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 wrote:
           | 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.
        
       | mike_ivanov wrote:
       | 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 wrote:
         | Doubtful. Shrooms cause seizures.
        
           | CacheRules wrote:
           | Sources?
        
             | __MatrixMan__ wrote:
             | 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 wrote:
               | 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 !
        
           | asveikau wrote:
           | Something tells me seizures have multiple causes and if the
           | drugs is one cause it's not a cause for everybody.
        
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