[HN Gopher] Psilocybin bests SSRI for major depression in first ...
       ___________________________________________________________________
        
       Psilocybin bests SSRI for major depression in first long-term
       comparison
        
       Author : Thomvis
       Score  : 374 points
       Date   : 2024-10-12 11:46 UTC (11 hours ago)
        
 (HTM) web link (www.medscape.com)
 (TXT) w3m dump (www.medscape.com)
        
       | newsclues wrote:
       | Taking LSD every few months was the best antidepressant I've ever
       | tried and I've tried a bunch
        
         | drcongo wrote:
         | This is surely no surprise to anyone who's ever had a good
         | trip. I'd love to do this in a proper, controlled therapy
         | setting, I suspect it would do me the world of good.
        
           | abyssin wrote:
           | You're right to explicitly mention the part about the good
           | trip. As always in this kind of discussions, there has to be
           | a reminder that psychedelics should be used cautiously, being
           | conscious about the risks associated with a potential bad
           | trip.
           | 
           | My only bad trip was in a proper, controlled therapy setting
           | -- at least that's how it was presented to me.
        
       | awestroke wrote:
       | I wonder how much of an uphill battle it will be to get
       | psilocybin approved for therapeutic use compared to synthetic
       | psilocybin analogues that are being trialed right now. Psilocybin
       | can't be patented and it's already scheduled as a narcotic
       | everywhere.
        
         | tootie wrote:
         | I'm taking a prescription med that is basically a schedule 1
         | drug that's been very slightly modified and declared schedule 3
         | and prescribed through a tightly controlled program. I'm even
         | taking a generic version.
        
           | mtlmtlmtlmtl wrote:
           | Purely out of curiosity, which drug is this, if you don't
           | mind me asking?
        
         | pier25 wrote:
         | It's already being used in therapy. Oregon is giving licenses.
         | 
         | https://www.oregon.gov/oha/ph/preventionwellness/pages/psilo...
        
           | Der_Einzige wrote:
           | In Oregon enforcement of what passes for our drug laws here
           | is so lax (cops quiet quit long before covid) that it's de-
           | facto legalized.
           | 
           | I've literally walked down Portland and had random homeless
           | people unprompted yell out "Want to buy some shrooms?"
           | 
           | There have been unlicensed openly practicing shrooms
           | businesses which survived far longer than one would expect
           | for such a "regulated" industry.
        
         | Muromec wrote:
         | I doubt about everywhere, as shrooms are sold in shop around
         | here.
        
           | chiefalchemist wrote:
           | Where is here?
        
             | foolfoolz wrote:
             | california has mushroom stores
        
           | dymk wrote:
           | In the US, those aren't from mushrooms that contain
           | psilocybin or related neurotransmitter analogs
        
             | snozolli wrote:
             | It definitely happens:
             | 
             | https://www.seattletimes.com/business/oregon-store-
             | allegedly...
             | 
             | https://www.sfgate.com/cannabis/article/sf-magic-mushroom-
             | ch...
        
         | cpucycling7 wrote:
         | Geneva is home to the only Swiss hospital offering psychedelic-
         | assisted therapy. [0]
         | 
         | Also, Peter Gasser, a Swiss therapist acquainted with LSD
         | during the 1988-1993 window, was granted approval to carry out
         | the first controlled study of LSD-assisted psychotherapy in
         | more than 40 years. [1]
         | 
         | [0] https://www.swissinfo.ch/eng/science/can-psychedelics-
         | therap...
         | 
         | [1] https://theswisstimes.ch/lsd-and-magic-mushrooms-how-
         | switzer...
        
         | Jerrrrrrry wrote:
         | The 2018 Hemp Farm bill gave the balls back to the citizens
         | that the 2013 Analag act neutered.
         | 
         | Seeing mushroom extracts with all the alkaloids included
         | besides psilocybin at gas stations may be a temporary point of
         | stability until I can go to the "21+" store in 2030 to get my
         | preferred arylcyclohexylamine and phenylethylamine variant.
        
           | dymk wrote:
           | From what I understand, those "magic mushroom" edibles sold
           | in head shops and gas stations are amanita muscaria derived,
           | which is a completely different psychoactive substance with
           | different alkaloids. Toxic to the liver too, in ways that a
           | cubensis is not.
        
             | tastyfreeze wrote:
             | Northern shamans drank reindeer urine after the animals had
             | eaten amanita muscaria. Passing through the animals reduced
             | the toxic component but left enough alkaloid to trip balls.
             | Maybe the gas station edibles have removed the toxin.
        
               | roywiggins wrote:
               | signs point to no:
               | 
               | https://www.cbsnews.com/news/magic-mushrooms-found-in-
               | recall...
        
             | Jerrrrrrry wrote:
             | I was aware but I should know to put disclaimers in drug
             | posts on HN at this point, as others may not be; thank you.
             | 
             | That being said, it did have an uncomfortable but brief
             | 'burning/cleansing' feeling reminiscent of Lyseragmides
             | that that most tryptamines / 4-aco-DMT / penis envy /
             | cubensis / 5-MEO-[xxx] did not, and more visual distortions
             | with notably less headfuckery / low body load.
             | 
             | I recommend a single try; the tolerance seemed to eliminate
             | effects nearly immediately.
        
       | ValentinA23 wrote:
       | https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
       | 
       | >Post-SSRI sexual dysfunction (PSSD)[62][63] refers to a set of
       | symptoms reported by some people who have taken SSRIs or other
       | serotonin reuptake-inhibiting (SRI) drugs, in which sexual
       | dysfunction symptoms persist for at least three
       | months[64][65][66] after ceasing to take the drug. The status of
       | PSSD as a legitimate and distinct pathology is contentious;
       | several researchers have proposed that it should be recognized as
       | a separate phenomenon from more common SSRI side effects.[67]
       | 
       | >The reported symptoms of PSSD include reduced sexual desire or
       | arousal, erectile dysfunction in males or loss of vaginal
       | lubrication in females, difficulty having an orgasm or loss of
       | pleasurable sensation associated with orgasm, and a reduction or
       | loss of sensitivity in the genitals or other erogenous zones.
       | Additional non-sexual symptoms are also commonly described,
       | including emotional numbing, anhedonia, depersonalization or
       | derealization, and cognitive impairment.[64][68] The duration of
       | PSSD symptoms appears to vary among patients, with some cases
       | resolving in months and others in years or decades;
       | 
       | https://www.pssdnetwork.org/
       | 
       | At least, the mushroom didn't steal my mojo
        
         | bitcurious wrote:
         | Can psilocybin restore the mojo, or are you just commenting on
         | the downside of SSRIs?
        
           | erie wrote:
           | One dude recounted how psilocybin helped him have the best
           | experience with the happy ending , as being out of this
           | world, but the timing was perfect, not sure if it was 'How to
           | Change Your Mind | | Netflix, or another one there.
        
             | hackernewds wrote:
             | happy ending?
        
               | 1986 wrote:
               | the little death.
        
           | ValentinA23 wrote:
           | Not a cure but a treatment (sample size: 1)
           | 
           | https://www.reddit.com/r/pssdhealing/comments/10tjyen/a_trea.
           | ..
        
         | johnnybzane wrote:
         | Within a few hours of taking zoloft I lost all sensation in my
         | genitals and it's stayed that way for years
         | 
         | I've since gotten all my hormones tested (normal), and doctors
         | are suggesting I cycle between TRT HCG & Clomid + Dopamine
         | Agonists
         | 
         | I don't have ED. My symptoms are purely genital
         | numbness/anorgasmia/failure to finish.
         | 
         | I submitted a complaint to the FDA last year. I understand
         | they're currently being sued over this.
         | 
         | I don't understand how SSRIs aren't classified as reproductive
         | toxins.
        
       | cpucycling7 wrote:
       | This has been common knowledge among mushroom friends for a long
       | time now. But it's always nice when the mainstream population
       | gets "something official" that helps them open up to knowledge
       | that is otherwise being censored quite everywhere.
       | 
       | Also, SSRI can definitely kill your sex life - and by extension
       | your relationship(s) as well. And not just short-term
       | (physiological changes have been observed). SSRIs have never been
       | the best option (except for pharmaceutical companies).
        
       | Mistletoe wrote:
       | It's a neat study. I don't know how you account for the intense
       | placebo effect of a psychedelic experience for six hours though.
       | We know that traditional antidepressants may work through this
       | method already where you feel "different" and fix yourself.
       | Trials with an active placebo often have results very similar to
       | antidepressants.
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
       | 
       | I guess maybe it doesn't even matter in the end as long as people
       | feel better.
        
         | delichon wrote:
         | > I don't know how you account for the intense placebo effect
         | of a psychedelic experience for six hours though.
         | 
         | If what they discovered is a particularly powerful way of
         | applying a placebo effect, that could be just as clinically
         | useful. Maybe more so since it could apply to more conditions.
        
         | strken wrote:
         | For obvious reasons you probably can't put a patient under
         | general anaesthetic before giving them either the placebo or
         | the drug, but I wonder what would happen if you did. Does a
         | patient have to be awake to see the antidepressant effect? How
         | do sedation and sleep differ?
        
           | ajb wrote:
           | There has been a study of that on ketamine, where they used
           | patients who needed to be put under anaesthetic for other
           | reasons. I'll try and find it in a bit...
           | 
           | Edit: found it https://www.astralcodexten.com/p/does-
           | anaesthesia-prove-keta...
        
         | BugsJustFindMe wrote:
         | > _I don't know how you account for the intense placebo effect
         | of a psychedelic experience for six hours though._
         | 
         | You don't need to. It doesn't really matter whether it's the
         | trip itself that works, the belief that a trip will work, or
         | some other aspect of the molecule. The drug category it's being
         | compared to also has its own placebo effects. It is entirely
         | reasonable to compare the complete holistic experience of
         | taking each.
        
         | ulrikrasmussen wrote:
         | This might not be ethical, but given a psychedelic naive
         | population, I wonder if the control could be given a non-
         | serotonergic psychedelic such as salvinorin A. There would
         | definitely be a noticeable effect, but for someone who hasn't
         | studied the effects of psilocybin, they may not realize it. The
         | downside is that in order to keep the duration similar, you'd
         | probably have to administer the salvinorin using an IV drip,
         | and a six hour salvia trip could quite possibly be too
         | traumatic.
        
           | parpfish wrote:
           | It might be nice to also have a non-psychedelic non-sari as
           | well. Right now a patient could use whether they tripped or
           | not to determine exactly which treatment they received. But
           | if you had the full 2x2 design of {drug has trip, drug has no
           | trip} x {drug is supposedly therapeutic, drug is non
           | therapeutic} the existence of a trip wouldn't reveal their
           | exact treatment
        
         | chiefalchemist wrote:
         | This is true of most if not all drugs / studies. That is, the
         | drug gets "credit" for the placebo effect. Sure they took the
         | meds, but that's correlation in at least some. That is, in some
         | the drug did not actuay work but they still get to benefit from
         | the placebo effect.
         | 
         | I rarely see this discussed. I'm not sure why (short of actual
         | cellular test showing it was the drug that did triggered the
         | success some of the success even in the group taking the real
         | meds is still the placebo effect).
        
       | dillydogg wrote:
       | I think a major criticism of how this study is designed is that
       | it is not truly "blinded". I doubt many of the participants were
       | unsure if they received psilocybin vs escitalopram.
       | 
       | That being said, there are a number of studies that suggest this
       | is an effective treatment, so I hope this can become more
       | available to those who need it. However, for treatment resistant
       | depression (especially with a catatonia component), intranasal
       | ketamine is very hard to beat. Only topped by ECT in my
       | experience.
        
         | RobotToaster wrote:
         | How would you effectively blind a study on a drug with such
         | obvious "side effects"?
         | 
         | I can see such unreasonable objections being used to prevent
         | it's approval though.
        
           | keepamovin wrote:
           | That was the "reason" the FDA nuked the MDMA approval.
           | "Unblinded because people could tell if they were on placebo
           | or active therefore how do we know it wasn't just placebo
           | effect based on belief"
           | 
           | Seems spurious as:
           | 
           | - 1) how do you reliably measure "people could tell"?;
           | 
           | - 2) if people sensed it, likely they can sense when they are
           | on active in a whole range of effective medicines, so seems a
           | biased / moved-goalpost application of the "rules";
           | 
           | - 3) what does it matter if the strength of the drug effect
           | is greater than the strength of the placebo? Ie, surely they
           | can model and subtract and control, so what does it matter if
           | the actual effect is more than placebo?
           | 
           | Ugh...
        
         | Jerrrrrrry wrote:
         | Having tried all the drugs, Ketamine and its cousins are very
         | "preppy" - the idealization and ruminating seem to be more
         | side-steppable; as if they were intrusive thoughts that were a
         | minor annoyance.
         | 
         | With the after-glow lasting weeks however, it seems to
         | facilitate/allow a period of self-reflection (using whatever
         | else possibly as an aide) that is notably absent of self-pity.
        
         | fullspectrumdev wrote:
         | The doses of psilocybin being used were so low as to be barely
         | perceptible.
        
           | jdietrich wrote:
           | The participants received a 25mg dose; I can assure you that
           | such a dose is _very much_ perceptible.
           | 
           | https://www.thelancet.com/journals/eclinm/article/PIIS2589-5.
           | ..
        
             | fullspectrumdev wrote:
             | Ah, I made a calculation error by an entire order of
             | magnitude while converting that to "grams of dried
             | mushroom".
             | 
             | Yeah that dose you would notice a fair bit - it's
             | equivalent to about 2.5g dried cubes.
        
         | kjkjadksj wrote:
         | Being blinded isn't some gold standard. For example we know
         | exercise leads to good health outcomes from unblinded studies.
         | Every study on fitness ever done is unblinded and we consider
         | these results to be a ground truth.
        
           | hx8 wrote:
           | The randomized controlled double-blind study is a gold
           | standard. It solves for so many different biases. Without it
           | the burden of proof is higher. Luckily, the evidence that
           | exercise is healthy is so overwhelming that we have a
           | scientific conciseness.
        
           | dredmorbius wrote:
           | "Parachute use to prevent death and major trauma when jumping
           | from aircraft: randomized controlled trial" (2018)
           | 
           | <https://www.bmj.com/content/363/bmj.k5094>
        
         | NickM wrote:
         | _I think a major criticism of how this study is designed is
         | that it is not truly "blinded". I doubt many of the
         | participants were unsure if they received psilocybin vs
         | escitalopram._
         | 
         | This is already a problem for most psychiatric drug trials;
         | studies have found that most people can tell if they're on an
         | SSRI or in a control group, since the side effects are pretty
         | noticeable.
         | 
         | There is evidence that this skews study results, to the point
         | that some scientists believe that SSRIs may only be "effective"
         | because the obvious side effects make them a good active
         | placebo.
        
       | jdietrich wrote:
       | Obligatory notes of caution:
       | 
       | The primary outcome of depression symptoms (QIDS-SR-16) was not
       | significantly different between the groups. The sample size is
       | small and unrepresentative of the real-world population of
       | depression patients - the trial participants are very
       | disproportionately male and university-educated. There are
       | obvious and much-discussed issues with blinding in psychedelic
       | trials.
       | 
       | These results point to a treatment that may be superior to
       | treatment-as-usual for a minority of patients, but the results
       | certainly aren't revolutionary. There is still the potential for
       | significant risk in wider clinical populations who may have
       | psychiatric comorbidities that would exclude them from trials
       | like this, and in delivering psychedelic treatments in more
       | normal clinical settings that are likely to be far less carefully
       | controlled than a clinical trial.
        
       | neom wrote:
       | Psilocybin saved my life. I'm no longer suicidal, I'm no longer a
       | practicing alcoholic, and outside of a few things here and there,
       | I'm generally at peace with my life. I cannot express how
       | grateful I am for psilocybin.
        
         | agumonkey wrote:
         | Is it something that you still take here and there or was it a
         | time limited therapy ?
         | 
         | Congrats on finding a cure for your ailments
        
           | infamouscow wrote:
           | Psilocybin tolerance starts building immediately. Even if you
           | microdose (100 mg), it will stop being effective after 3-4
           | days.
        
             | vlabakje90 wrote:
             | 100mg psilocybin is several times a heroic dose, but 100ug
             | is far below a microdose. Do you mean 100mg of dried
             | mushrooms?
        
               | dymk wrote:
               | I think he means 100mg of mushroom body, which might be
               | 1-2mg of psilocybin.
        
             | dymk wrote:
             | Tolerance also wanes quickly. In 3 days of abstaining,
             | you're nearly entirely back to baseline tolerance. In 2
             | weeks you're entirely back to baseline.
        
             | hilux wrote:
             | Is there evidence of this?
        
           | neom wrote:
           | I did 3 sessions of 8 grams in silent darkness for 3 weekends
           | in a row and that basically "beat the devil out of me" as
           | they say - it was very very difficult, and a lot of work, but
           | well worth it.I've only felt the "brain haze" (I call it)
           | once since then, I took a gram and went for a long walk in
           | the forest, back to no haze. It's been about 7/8 months and I
           | can feel the "haze" building in my mind again, so I plan to
           | do another 1g in the forest sometime in the coming weeks.
           | 
           | However, my personal experience has been that Psilocybin !=
           | Psilocybin - the mushroom itself is super important to the
           | process, much like Indica and Sativa have different ways of
           | connecting you to the mind and the aether, Psilocybin (at
           | least for me) VERY much is the same thing, and it's much
           | starker than cannabis is. Getting into woo-woo land here so
           | apologize: I have some concern that just "Psilocybin" isn't a
           | good prescription, that the "spirit" that works on you is
           | unique to the mushroom family, and that both not knowing the
           | mushroom to prescribe and also being clinical about it
           | (Psilocybin vs Mushroom) may not be a good direction to go in
           | to help people with their issues. I also think that about
           | LSD, it might work a bit for a while, but imo it's not the
           | best tool.
        
             | samatman wrote:
             | Anecdotal case study involving a community of about a
             | hundred enthusiasts: many in this community held the
             | opinion you do, which is that something about the mushrooms
             | themselves is unique to the psilocin experience (psilocybin
             | is not always present, and in any case, metabolizes to
             | psilocin).
             | 
             | Then 4-actyl DMT, sometimes call psilacetin, became broadly
             | available. This is a synthetic pro-drug for psilocin, just
             | as psilocybin is a naturally-occurring pro-drug for
             | psilocin.
             | 
             | After that, the opinion that the mushroom _per se_ had
             | anything to do with the experience became very rare. It
             | turns out that psilocin is meaningfully different from, in
             | particular, LSD, 2C-B, and MD(M)A.
             | 
             | There's definitely something special about it. But that
             | something is also present when it comes in vitro, not just
             | in vivo.
        
             | tristanMatthias wrote:
             | Totally agree. The variance between species can be
             | dramatic! 2.5 grams of Golden teacher was a standard trip,
             | vs 0.5 grams of PES Amazonian was enough to send my friend
             | into a full blown "awakening" (physical responses and
             | everything).
             | 
             | It's fascinating how they can hit different.
             | 
             | Also important to keep in mind the same dose can hit
             | someone different each time depending on surrounding life
             | conditions. I'm a big believer that the mushrooms "show you
             | what you need to see" at any given moment, and that can
             | sometimes range considerably.
        
               | andoando wrote:
               | It's really hard to say because your mental state of
               | being, how tired/hungry/etc you are, and thr environment
               | you take it in are huge factors.
               | 
               | Taking it alone vs with friends is going to be a dramatic
               | difference on its own, just because of what neural
               | pathways are active when you take them.
        
             | namaria wrote:
             | I'm of the opinion that psychedelics can fulfill a similar
             | role to religious catharsis for the maintenance of mental
             | health.
        
             | andoando wrote:
             | 8 grams in one sitting? Im not even so worried about the
             | psychological response but even a gram can give me extreme
             | stomach pain and nausea that ruins the whole thing.
        
               | xkcd-sucks wrote:
               | making a tea with slightly acidic not-too-hot water helps
               | quite a lot
               | 
               | also chewing fresh ginger or ginger tea
               | 
               | starting on an empty stomach, of course
               | 
               | but surprisingly, sometimes a little bit of miso soup
               | midway can help with the "gastroparesis" type nausea that
               | can emerge late stage
               | 
               | and also a little bit of diphenhydramine if it's still
               | bad (like less than an antihistamine dose)
               | 
               | even if it is all kind of lipstick on a pig :)
        
         | M4v3R wrote:
         | Thanks for sharing this, you're not the only one. I have a
         | close friend who tried LSD as a last resort to get the best of
         | his severe depression and suicidal thoughts (after being on
         | SSRIs for his entire life) and just one session completely
         | removed his suicidal thoughts for _months_. After this
         | experience he repeats this whenever he feels the dark thoughts
         | are coming back and it always curbs them down almost
         | completely. It's mind-blowing how well it worked for him.
        
           | fsckboy wrote:
           | just consider, if it's so powerful in adjusting his brain,
           | it's probably equally powerful in adjusting anybody's brain,
           | and what if your brain doesn't need adjustment? there's no
           | reason to think it's "idempotent" so to speak.
           | 
           | https://en.wikipedia.org/wiki/Idempotence is the property of
           | certain operations in mathematics and computer science
           | whereby they can be applied multiple times without changing
           | the result beyond the initial application
        
         | foobiekr wrote:
         | Same. I came to them as an older person (late 40s) who
         | basically had only tried pot a few times prior, and nothing at
         | all before late thirties. I don't drink.
         | 
         | My few experiences, the first few times, over the course of a
         | year, spread apart by 3-4 months, went from extremely dark to
         | .. just positive, except the last one, where I had no visuals,
         | no bliss at all, and just came to terms with something else in
         | our lives that was going wrong.
         | 
         | The dark ones were rage and anger, and now it seems just gone,
         | like there's nothing there. Like a weight lifted, and seemingly
         | long term.
        
         | ghnws wrote:
         | SSRIs did the same for me.
        
         | whalesalad wrote:
         | Same. Grew them myself. Microdose regularly. Take big trips
         | once in a while. It completely changed my life.
        
         | hilux wrote:
         | That is so wonderful to hear!
        
         | andoando wrote:
         | Can you share some info on how much you took, and in what
         | setting you took them, what you did on the trip, etc? I have a
         | bunch of shrooms sitting in my cabinet but I havent had got any
         | life altering effect out of them.
        
       | 8b16380d wrote:
       | Funny, psilocybin has been largely detrimental to the mental
       | health of everyone I know.
        
         | api wrote:
         | In what way were they using it? In what dosages? Was it
         | pharmaceutically pure or bought from some dude?
         | 
         | Overdosing on SSRIs or using them haphazardly could be pretty
         | detrimental too.
        
         | mouse_ wrote:
         | my experience has been very different for everyone I know
        
         | joemazerino wrote:
         | Agreed with a caveat: SSRIs and other antidepressants are far
         | worse.
        
         | giantg2 wrote:
         | "Funny, psilocybin has been largely detrimental to the mental
         | health of everyone I know."
         | 
         | This statemwnt is true for the people I know who have used it
         | in a recreational manner. This statement is also false for the
         | people I who who have self-treated with it in a controlled
         | setting.
        
         | standardUser wrote:
         | I've have done a _lot_ of drugs and know a lot of people who
         | have done a lot of drugs, and psilocybin is far and away the
         | substance that is most loved and gets the best reviews. It 's
         | not even close.
        
           | Der_Einzige wrote:
           | Thoughts on Mescaline/Peyote?
        
             | standardUser wrote:
             | I've known far fewer people who have taken it. Unlike
             | mushrooms, I have heard stories of prolonged and difficult
             | trips that sound much more challenging and arguably
             | dangerous than a average-dose mushroom trip.
        
             | foobiekr wrote:
             | Mescaline is like the angry lover version of mushrooms. I
             | did it once, two years ago to understand why it has been
             | used, traditionally, as the baseline for comparison for
             | psychedelic substances, and it was enlightening; it is
             | certainly a tasting menu of the classical psychedelics,
             | having at different points in the experience the flavor of
             | stimulants, LSD, mushrooms and finally something all its
             | own, but it is also much grittier and less loving than
             | mushrooms.
             | 
             | Mescaline is _rough_. And honestly the "you are done with
             | it before it is done with you" thing is 100% true, it is
             | also very long lasting.
        
           | romseb wrote:
           | What are the more preferred plants/substances for personal
           | growth and mental health?
        
       | state_less wrote:
       | > "Psychiatrists really focus on negative symptoms of depression.
       | So, if you are not sad anymore, if your sleep or appetite is not
       | impaired, they think you're better. But if you look at what
       | patients define as important, they say it's the degree in which
       | their life is meaningful, in which they can connect with people
       | around them, in which they can function in everyday life," Barba
       | said.
       | 
       | A more wholistic approach to health care would be beneficial. For
       | folks looking for more depth or purpose, Psilocybin seems to help
       | reconnect people with a part of themselves they only dimly
       | remember.
       | 
       | I often hear people talk about the risks of psychedelics, which
       | are to be considered, but what's the risk of doing nothing or
       | withholding the best treatment?
        
         | phoronixrly wrote:
         | > I often hear people talk about the risks of psychedelics,
         | which are to be considered, but what's the risk of doing
         | nothing or withholding the best treatment?
         | 
         | The risk is to make things worse.
         | 
         | And I know that I am preaching to people that are of the
         | opinion that they know better than the FDA, scientists and
         | doctors and are all for self-medicating based off of the echo
         | chamber here and a few cherry-picked, limited and flawed by
         | default (like in the case of this one) studies on the first
         | page of Google.
        
           | HKH2 wrote:
           | I don't want people self-medicating with psilocybin, just
           | like I don't want people self-medicating with SSRIs.
           | 
           | Which is more dangerous?
        
             | phoronixrly wrote:
             | The best thing to do is to consult with a physician on
             | matters related to your health.
        
               | maeil wrote:
               | That's not clear cut. There clearly exist plenty of
               | combinations of "situation + physician" where this is
               | _not_ the best thing to do. To claim otherwise may as
               | well be religious dogma.
        
               | phoronixrly wrote:
               | I'm sorry, but how is trusting a person who dedicated 10+
               | years of their life studying/practicing this, and relying
               | on rigorous safety and effectiveness research of drugs
               | religious dogma? Are you sure you know what religion is?
               | Are you sure you know what science is? Are you just
               | trolling?
        
               | beagle3 wrote:
               | If you actually read the effectiveness and safety
               | research with a critical eye, you would realize
               | "rigorous" is often the wrong adjective, whereas "cherry
               | picked" to the point of "fraudulent" is often more in
               | line with reality.
               | 
               | Case in point: 50,000 people died, with about 5 times as
               | many suffering life-changing serious adverse events, from
               | "rigorous research" on the safety of Vioxx. Yes, it has
               | since been pulled from the market, which FDA apologists
               | often construe as "system working as designed". No, it
               | isn't, even in the least, when you go into the details.
               | 
               | Also: Purdue and OxyContin.
               | 
               | Regulatory capture of the FDA is decades old at this
               | point. Ignoring that is not a rational or healthy
               | position.
        
               | farts_mckensy wrote:
               | I don't know, why don't we ask my colon? Oh, wait, we
               | can't. I was prescribed accutane, subsequently got
               | ulcerative colitis so bad that they had to remove the
               | organ entirely. The surgeon said my colon was literally
               | falling apart in his hands as he took it out. Blind
               | deference to authority of doctors lead to this situation.
               | They do not always make great decisions, especially if
               | there is a financial incentive for them to do otherwise.
        
               | bobthepanda wrote:
               | At the very least, consulting with one or more physicians
               | gives more data points than you would otherwise have. If
               | your goal is to know more, having other opinions is
               | pretty fundamental.
        
               | dingnuts wrote:
               | that's easy to say when you forget about the state of
               | healthcare.. everywhere, actually. I was going to say the
               | US but in other countries it's not like you can just pop
               | in for a chat about taking shroomies, either.
               | 
               | I'm not sure having a ten minute meeting with a stranger
               | who has a PhD in internal medicine is going to yield
               | useful strategies for curing the existential dread
               | underpinning your depression whether you're there to
               | discuss getting zonked on LSD or something more
               | "traditional" like Xanax
        
               | phoronixrly wrote:
               | > it's not like you can just pop in for a chat about
               | taking shroomies
               | 
               | You sure can just pop in to discuss options for your
               | crippling depression though? And sorry, I do indeed live
               | in a country with a functioning healthcare system, not
               | the US.
        
               | dingnuts wrote:
               | In the US normally you talk to a therapist (not a doctor)
               | or psychologist (not a medical doctor) about your
               | depression at length, and then if you're deemed
               | sufficiently depressed you get a short consult with a
               | psychiatrist (finally a doctor) to prescribe medication.
               | This is when you would theoretically finally be able to
               | bring up shrooms, and your psychiatrist will laugh at
               | you, write an Rx for an SSRI, and you'll see him next
               | year when the Rx expires
               | 
               | I'm not sure how it is in most countries but I'd expect
               | the biggest difference is that it will cost you money in
               | the US, but I've read many many horror stories about
               | people waiting many months to have only a short chat with
               | a physician from other countries. The lack of time
               | available to spend taking to physicians seems to be a
               | problem in other places too
               | 
               | my point is that consulting a doctor with random
               | questions isn't a simple, casual thing people can easily
               | do in most places. in most places you have to plan ahead
               | and either wait a long time for an appointment, and/or
               | there is a cost barrier.
               | 
               | if you have examples of countries where people are able
               | to get to know their doctors on a personal level and can
               | afford in time and money to talk to their physicians for
               | more than a few minutes per year, please link them below
        
               | standardUser wrote:
               | The US government severely restricts research on Schedule
               | 1 drugs like psilocybin. Physicians don't have the data
               | they need to inform patients.
        
               | Der_Einzige wrote:
               | The idea that doctors aren't constantly "off base" and
               | must be deferred to uncritically is pretty terrible.
               | 
               | For example, it took literally two decades after it
               | became well known that peptic ulcers were mostly caused
               | by bacteria for the medical community to embrace giving
               | anti-biotics for GI pain. To this day, there are still
               | many American doctors who don't actually know about the
               | Nobel Prize given in 2000 for this discovery, and claim
               | it's "stress" and tell you to go home. Some claim they
               | "know" but than try to "change your gut PH" and still
               | refuse to give antibiotics due to "superbug" risk.
               | 
               | This is a "small" thing (GI pain is not small to those
               | who have it) - but if the doctors are screwing up such a
               | small thing institutionally, what else do they mess up
               | on?
               | 
               | One is travelers sickness. Doctors in the USA do not want
               | to perscribe front line antibiotics for it because of
               | fear of superbugs - but they'll uncritically go eat their
               | lunch at a McDonalds that same day, where they consume
               | meat bathed in antibiotic slop which is more likely to
               | contribute to superbugs then the amoxicillin that they
               | didn't give you would have.
               | 
               | Or what about right now, when it's become clear that
               | Ozempic is literally a super-drug. Every doctor on earth
               | should be trying to give that stuff to literally anyone.
               | 
               | I can go to "third world countries" with deregulated
               | health systems and get infinitely better care that I have
               | real control over for on the orders of 1 USD (that's how
               | much it cost for me in Thailand to get front line
               | antibiotics for travelers sickness INCLUDING THE DOCTORS
               | VISIT!)
               | 
               | Why do we still sell Neosporin despite doctors wanting it
               | off the market (also for risk of superbugs)? Why do few
               | people in America use Providone-iodine for wound
               | treatment despite it being by far the best solution
               | scientifically for it (and it stains yellow)? Maybe it's
               | because we're stupid. There really aren't better
               | explanations.
               | 
               | What about Circumcision? I'd straight up put doctors who
               | do it in jail and many European nations would do the
               | same. American doctors think circumcision is just fine,
               | and long, deeply bitter swaths of medical ethics journals
               | are dedicated to fighting over this again and again.
               | 
               | Or what about the widespread disagreement over even basic
               | stuff like digital rectal exams? There's no agreement on
               | if they are worth it because often sticking one's hand up
               | the butt of an old man does more damage to them than
               | finding out that they (like everyone else at old age)
               | have benign prostate cancer?
               | 
               | Doctors in America have not earned their position of
               | deference. The scientifically minded on HN who do their
               | own research can and often do know how to treat certain
               | conditions better than white-coats.
        
               | m_fayer wrote:
               | I really wish we would retire this chestnut already. As
               | if there's a reasonable grownup option here and
               | everything else is playing with matches.
               | 
               | No it's not the best thing to do to brave huge waiting
               | lists, call a hundred providers none of whom are taking
               | new patients, pay a fortune out of pocket, and/or be
               | faced with a distracted impatient person stuck to their
               | screen who has 10 minutes for you.
               | 
               | And I live in Germany, not the US.
        
             | striking wrote:
             | Psylocybin? Easily?
             | 
             | You have to put effort into making an experience with
             | psylocybin meaningful and helpful. It could go wrong very
             | easily, especially for those who are in a difficult
             | situation or headspace. (Speaking from experience.)
             | 
             | As for SSRIs? Safe, effective, with a handful of annoying
             | side effects. Straightforward to use, low potential for
             | misuse, requires sustained use for any intended effects. A
             | doctor who already has familiarity with a patient's mild or
             | moderate symptoms of anxiety or depression may very well
             | just prescribe one if asked and if not contraindicated. Not
             | that you should randomly start popping Prozac, but it's
             | unlikely to hurt you if you did.
             | 
             | Ask your doctor, try the things that doctors currently
             | believe are most likely to work first. If for whatever
             | reason you choose to go beyond the current medical
             | consensus, please stay safe and keep your doctor up to
             | date.
        
               | HKH2 wrote:
               | So are you okay with people choosing their own dose of
               | SSRIs?
        
               | standardUser wrote:
               | A prescribing doctor will not magically know the precise
               | amount of an SSRI a patient should be taking, or which
               | one to take. For most patients, finding the right drug
               | and dosage is a process. And just like with psilocybin,
               | no one would want to take a _random_ amount. Like with
               | any drug, a person would want to be informed and have
               | proper guidelines about dosage from the start.
        
               | jorvi wrote:
               | > Psylocybin? Easily?
               | 
               | Err.. no?
               | 
               | This is from the Dutch National Institute for Public
               | Health and the Environment:
               | https://www.rivm.nl/bibliotheek/rapporten/340001001.pdf
               | 
               | Page 19 onward has the charts. What do do we find at the
               | very low end in terms of chronic and acute toxicity?
               | Shrooms ("paddos") and LSD.
               | 
               | It always blows my mind how anti-drug people will do a
               | handwavey gesture to the authority of institutes like the
               | FDA, but never actually check up on what actual research
               | says.
               | 
               | > As for SSRIs? Safe, effective, with a handful of
               | annoying side effects.
               | 
               | Except the multitude of ways you can put yourself into a
               | serotonin coma.
               | 
               | I agree with your assessment that (first) use of
               | psychedelics should be under proper guidance. But what
               | you refer to, "going bad", can sometimes be a traumatic
               | past experience that people have stuffed away and by
               | surfacing and processing it they can move past it. It's
               | not always meant to be kumbaya and flowers.
               | 
               | Educate yourself, then talk.
        
               | striking wrote:
               | I'm not saying psylocybin can't be used safely, nor have
               | I made any claims about its relative toxicity or harm
               | relative to other scheduled drugs. If you're arguing
               | anything else, I don't think that report says what you
               | think it says. As for my position, I live in SF, it's
               | decriminalized here, I support that. So there's no need
               | for your rude presumption that I find it generally
               | unsafe.
               | 
               | I'm also unfamiliar with the dose of SSRIs that would
               | send you into a coma, but I'm fairly certain it's
               | shockingly large. Happy to be informed otherwise.
               | 
               | edit to reflect parent edit: yes, I'm aware that
               | breakthrough experiences can be helpful. I'm also saying
               | they should not be your first resort.
        
               | wizzwizz4 wrote:
               | > > You have to put effort into making an experience with
               | psylocybin meaningful and helpful. It could go wrong very
               | easily, especially for those who are in a difficult
               | situation or headspace. (Speaking from experience.)
               | 
               | > _What do do we find at the very low end in terms of
               | chronic and acute toxicity? Shrooms ("paddos") and LSD._
               | 
               | Breaking your mind doesn't count as toxicity. You're not
               | responding to the point you tried to refute.
        
               | worik wrote:
               | > Breaking your mind doesn't count.....
               | 
               | Hyperbole
        
               | hackernewds wrote:
               | toxicity is the least of _psychoactive_ drugs problems
        
               | farts_mckensy wrote:
               | Impotence and weight gain are not just "annoying" side
               | effects. They seriously impact your life. Just putting
               | that out there.
        
               | striking wrote:
               | I'm not claiming they don't. Everyone experiences SSRIs
               | differently and it's common to shop around until you find
               | one whose side effects impact your life in a more
               | tolerable way.
               | 
               | That's in contrast to psylocybin, which has substantially
               | more serious potential acute side effects, ones that are
               | more difficult to understand and treat should they occur.
               | 
               | I'm not saying psylocybin is unsafe or that SSRIs are
               | always preferable. But if I'm asked to compare their
               | safety? The choice is obvious, weight gain
               | notwithstanding.
        
               | NickM wrote:
               | _I 'm not claiming they don't._
               | 
               | You were clearly implying they don't when you downplayed
               | all SSRI downsides as "a handful of annoying side
               | effects".
               | 
               | Weight gain kills. Suicidal ideation also kills many
               | people when they start SSRIs. People have killed
               | themselves because of permanent sexual dysfunction caused
               | by SSRIs that never went away after stopping the drugs
               | (and yes, this is a known possible adverse effect listed
               | in the official prescribing information).
               | 
               | I don't think the choice is as "obvious" as you're making
               | it out to be.
        
               | striking wrote:
               | I wasn't aware of PSSD (I don't seem to be alone on that
               | front).
               | 
               | Leaving this link for others to pick up for more
               | information: https://annals-general-
               | psychiatry.biomedcentral.com/articles...
        
               | LocalH wrote:
               | I guarantee you the number of people who have died from
               | SSRI misuse is higher than the number of people who have
               | died from psilocybin misuse. I'm not referring to things
               | a person may do in a given state, I'm talking about
               | effects from the drugs themselves. I'm not aware of a
               | single recorded person who has taken _any_ dose of
               | psilocybin, and died from  "psilocybin overdose". While
               | it may be uncommon, it is possible to overdose on SSRIs.
        
               | striking wrote:
               | Sure, psylocybin won't kill you, but the threat of
               | inescapable psychological distress is real. Maybe it's
               | less likely if you aren't predisposed to psychosis, but
               | you can't easily know for sure that you're not.
               | 
               | And yes, it's possible to misuse SSRIs, but taking an
               | obviously oversize dose is still often a treatable
               | situation. Combining them with depressants I think is a
               | degree of misuse that is incomparable.
        
               | worik wrote:
               | > but the threat of inescapable psychological distress is
               | real.
               | 
               | Really?
               | 
               | That is true of any meaningful experience
               | 
               | The danger with psychedelic drugs is very low
               | 
               | They wear off
        
               | dustyventure wrote:
               | While fishing for that right dosage of SSRIs you have a
               | person with new boughts of mania and suicidal tendencies
               | where there's no clarity on how to stop the experiment
               | due to the complexity of blood level accumulation.
               | 
               | If SSRIs started as illegal drugs, with i.e. people
               | starting them dodging medical supervision, I think the
               | system would be telling us they are insanely risky and
               | well beyond many scheduled drugs.
        
             | dyauspitr wrote:
             | Definitely psilocybin. For instance, if you take psilocybin
             | and then spend some time in a cow slaughterhouse house, you
             | might go crazy. The same wouldn't be true of SSRIs.
        
           | tastyfreeze wrote:
           | Many people here are speaking from experience. I trust my own
           | judgment over some knob in the FDA that is steeped in a
           | culture of drug control.
        
             | phoronixrly wrote:
             | > Many people here are speaking from experience. I trust my
             | own judgment over some knob in the FDA that is steeped in a
             | culture of drug control.
             | 
             | Let me paraphrase this:
             | 
             | Many people here are parroting stuff based on a sample size
             | of 1, who lived to tell the tale. You trust your own
             | judgement based on those people before the rigorous safety
             | and effectiveness studies for the FDA, on a whim that the
             | FDA approves or rejects drugs based on their... ? Culture
             | of hating recreational drugs?
        
               | tastyfreeze wrote:
               | The FDA exists to tell you, a free individual, what you
               | are allowed to put in your body. It has been a very long
               | time since the FDA has been about safety only. It is
               | wholly captured by business interests in food and drug
               | industries. So yes, they, and the government culture as a
               | whole, hate recreational drugs that they don't control in
               | some way. No shooms for you but drugs that cause suicidal
               | ideation are prescribed by the millions.
               | 
               | I am wary of people "looking out for your safety" when
               | there is financial incentive to do otherwise.
        
               | tikhonj wrote:
               | Schedule I drugs specifically? The regulation around them
               | is inescapably rooted in a culture of hating recreational
               | drugs.
        
           | farts_mckensy wrote:
           | Is there any evidence that psilocybin "makes things worse" or
           | are you just concern trolling?
        
             | DiscourseFan wrote:
             | Probably not...the question is, does Psilocybin have a
             | higher incidence rate of users suffering episodes of severe
             | depression or psychosis than, say, SSRIs. Amongst all the
             | "spiritual" drugs, even counting THC, Psilocybin is the
             | most well tolerated--even so, SSRIs tend to still be very
             | safe, even if they are not very effective.
        
             | phoronixrly wrote:
             | The best thing to do is to consult with a physician on this
             | matter, even if side effects, drug interactions and
             | precautions are readily available and cardiac arrest and
             | death are among them. Idk, is this worse?
        
           | WhitneyLand wrote:
           | My suspicion has always been the majority of adverse
           | reactions have related to improper dosing.
           | 
           | Anyone can have a horrible response with too high of a dose
           | yet with self-medicating theres no sure way to know the
           | amount of medicine you've ingested even if weighing.
        
             | phoronixrly wrote:
             | Rigorously determining the proper effective and safe dose
             | is part of the approval process.
        
           | layer8 wrote:
           | > The risk is to make things worse.
           | 
           | That risk exists in many medical interventions. We need to
           | quantify that risk and weigh it against the chances of making
           | things better.
        
             | wizzwizz4 wrote:
             | This is generally what the regulatory system tries to
             | accomplish.
        
               | biorach wrote:
               | Right. But there was Oxycontin. So it's obviously got its
               | flaws.
        
           | dimal wrote:
           | And psychiatric drugs don't ever make things worse? As
           | someone who was severely injured by FDA approved,
           | scientifically validated medications, I'd say some healthy
           | distrust of a corporate-captured bureaucracy is warranted.
           | Remember, OxyContin was FDA approved. Did the FDA ever launch
           | an investigation into how they allowed that disaster to
           | happen? No. They didn't so much as say "whoops".
        
         | delusional wrote:
         | > A more wholistic approach to health care would be beneficial.
         | 
         | Maybe. My personal experience has been that those "negative
         | symptoms" were in fact the entire disorder. I didn't need
         | purpose or depth. I needed to not be so sad that I couldn't
         | function. I needed to be able to hold a coherent thought for 5
         | minutes without getting stuck into a negative spiral of self
         | loathing.
         | 
         | I want "purpose" and "connection", but those things are what
         | everybody on earth are looking for. The search for those things
         | is the _stuff_ that life is made of. I needed help to get back
         | to a place where I could pursue those things. Pursuing them is
         | my life.
        
         | photochemsyn wrote:
         | The article discusses the risks of treatment:
         | 
         | > 'He added a word of caution for therapists that "psilocybin
         | requires active confrontation of painful, negative emotions and
         | people who take this drug need to be open and prepared for the
         | idea that they are going into a state where they may probably
         | end up crying and confronting whatever they are maybe running
         | away from in their lives. Not everyone may want to do this."
         | 
         | The long-term consequences of trying to avoid such issues seem
         | considerable, e.g. it might lead to schizophrenia if people try
         | to wall off parts of their memories they find intolerable,
         | though that's just speculation at this point.
        
         | JumpCrisscross wrote:
         | > _Psilocybin seems to help reconnect people with a part of
         | themselves they only dimly remember_
         | 
         | Is there science behind this statement?
         | 
         | From what I know, we understanding psychedelics work. We don't
         | know precisely how.
        
         | roughly wrote:
         | > A more holistic approach to health care would be beneficial.
         | 
         | I've commented on this elsewhere, but with psychedelics in
         | particular we wind up in a weird space around our normal
         | approaches to health - for instance, there's a lot of effort
         | right now on finding the chemical mechanisms by which
         | psychedelics affect mood, with the goal of creating substances
         | which have the same impact on depression without the
         | phenomenology of the trip. My suspicion is the trip is the
         | treatment, or at least part of it - that the experience of
         | being in an entirely different mindstate, of reacting to the
         | world in a fundamentally different way using different mental
         | pathways for several hours - is a core part of the treatment.
         | Medicine has a bad habit of ignoring the patient's lived
         | experience - to look at the patient broadly as a mechanism, and
         | particularly as a collection of mechanisms, and to see things
         | like hypertension* as something to be treated with a chemical
         | offset and not a reflection of the full factors of a person's
         | life. My hope is that the psychedelics will help us recognize a
         | paradigm shift here (like, in data leading to changes in
         | practice, not just in their normal way), but I think they've
         | still got too much of the taint of the hippie on them to really
         | be taken seriously.
         | 
         | * I'm using hypertension as just an example of a particular
         | ailment, I'm not making a statement on the treatment
         | hypertension in particular.
        
       | keepamovin wrote:
       | But no patent, so this is "misinformation" haha
        
       | chiefalchemist wrote:
       | When this topic comes up on HN I'm always sure to mention the
       | book:
       | 
       | "How to Change Your Mind" by Michael Pollan
       | 
       | There's also a Netflix doc series based on the book.
       | 
       | https://michaelpollan.com/books/how-to-change-your-mind/
        
       | sub7 wrote:
       | I do LSD once a year with close friends and a beautiful view and
       | it's fantastic at making me appreciate beauty in the world and
       | feel like everything is in it's natural place.
       | 
       | Shrooms sadly do not agree with my digestive system.
        
       | cubefox wrote:
       | Unfortunately it's hardly possible to do proper case control
       | studies with psilocybin, since the psychedelic effects cause
       | unblinding. The participants know whether they are in the
       | treatment or control group.
       | 
       | > Normally the journey is quite inward, so patients do not
       | require active support during the psychedelic experience [around
       | 6 hours]. Sometimes they do require some hand-holding, or helping
       | them to 'let go', or breathing exercises. The important part is
       | the integration work that comes afterwards," Barba added. [...]
       | 
       | > However, [Rucker] noted, it is also possible that the results
       | reflect biased reporting between groups. This is more likely here
       | because studies involving psilocybin tend to attract those with
       | positive preconceptions about psilocybin and negative
       | preconceptions about conventional antidepressants
        
         | teaearlgraycold wrote:
         | You could compare against other psychedelics. I'd be interested
         | in that.
        
           | zozbot234 wrote:
           | You could also test it on severely sleep-deprived
           | experimenters undergoing sensory isolation, but that would
           | never get IRB approval.
        
             | roywiggins wrote:
             | Sleep deprivation is thought to temporarily relieve
             | depression in a lot of people, so it wouldn't really be a
             | placebo anyway.
             | 
             | https://www.pennmedicine.org/news/news-
             | releases/2017/septemb...
        
           | cubefox wrote:
           | Yeah. Especially a comparison with LSD seems interesting.
           | However, if both perform similarly, this could either mean
           | they both work or they both don't work.
        
         | kjkjadksj wrote:
         | Hardly an issue. When people do similar studies measuring say
         | the effects of prescribed exercise vs not they are also
         | unblinded but we still get good data.
        
         | hx8 wrote:
         | If there is a medical question that double-blind studies cannot
         | answer, that doesn't mean the question is unanswerable. It
         | means we should be more skeptical of non-blinded studies (or
         | worse studies that pretend to be blind), and we should look for
         | alternative ways to address biases.
        
         | dontwearitout wrote:
         | I've never found it compelling that blinding isn't possible for
         | drug-naive patients. There are other drugs that could induce a
         | "trip" and an unfamiliar individual could mistake for a minor
         | psychedelic experience.
        
         | NickM wrote:
         | _Unfortunately it 's hardly possible to do proper case control
         | studies with psilocybin, since the psychedelic effects cause
         | unblinding._
         | 
         | This is a problem with SSRIs as well; studies have found most
         | people can correctly guess if they're in the study group or
         | control group.
         | 
         | A true double blind study would require a drug that has similar
         | side effects via an unrelated mechanism, but nobody has
         | attempted that as far as I'm aware.
         | 
         | There was this interesting one though where they deceived
         | patients into believing they were taking an "active placebo"
         | instead of an SSRI, and found that the benefits went away,
         | which is very interesting and raises a lot of questions about
         | the true efficacy of these medications:
         | https://www.nature.com/articles/s41398-021-01682-3.pdf
        
       | iluvcommunism wrote:
       | It'll be good to find positive effects in natural remedies like
       | this. It is ironic we try to keep people safe from themselves but
       | end up dolling out ineffective or destructive drugs instead. A
       | case in point, opium being illegal, but a lab derivative 1k
       | stronger fentanyl, legal and 300k killed globally over the last
       | 10 years.
        
         | bobthepanda wrote:
         | Where are you that fentanyl is legal in a way opium is not? In
         | the US both are schedule II and approved for medicinal use.
        
           | thfuran wrote:
           | And it's mostly not legally acquired fentanyl that's killing
           | people.
        
       | lumb63 wrote:
       | Exercise also bests SSRIs. Having had multiple close family
       | members and friends try various cocktails of SSRIs and other
       | drugs for depression, bipolar disorder, and borderline
       | personality disorder, and having to see the side effects they
       | experience, and how many different dosings and combinations need
       | to be tried before they find something that doesn't _make them
       | worse_ , I would not recommend such medication to anyone with
       | similar issues without trying other more conservative approaches
       | first.
        
       | DiscourseFan wrote:
       | Ok like most of you I've taken psychedelic drugs. I've had bad
       | experiences sure, but I'm fine now.
       | 
       | The issue is that what people generally say, like, "oh sometimes
       | you need to encounter your demons," maybe that will be
       | temporarily traumatizing--in general people recover from that.
       | The real issues are...more complex. More complex than any
       | diagnoses in the DSM can cover. The brain is very complicated,
       | and everyone's brain is a bit different, and we do not know,
       | really, what goes on in there when you take a drug like
       | Psilocybin. Sometimes something gets a little knocked out of
       | place, and the system doesn't fully recover.
       | 
       | The last time I took a very high dose of psychedelics I couldn't
       | think straight for a few weeks after. Thoughts came out of
       | nowhere, I had no control over them; often the constant,
       | unceasing flow of thought was distressing and uncomfortable.
       | Thankfully I could still talk to people--talking made me better.
       | I got plenty of sleep, cut out all drugs, even caffiene, got
       | regular exercise and ate a very healthy diet: about a year and a
       | half later I was back to my old habits. But it wasn't an easy
       | recovery, and certainly not one any psychiatrist could've treated
       | adaquetely. But, now I know to be more careful in the future.
        
         | zozbot234 wrote:
         | Taking psychedelics is a bit like trying to fix a Swiss watch
         | with a sledgehammer: it might just work, but that's not the way
         | to bet. Therapy and well-guided meditative practice can be a
         | lot gentler than that.
        
           | bandyaboot wrote:
           | This is sort of how the mechanism of psychedelics fixing
           | depression comes across to me as well. But, surely there must
           | be much more to it, since, as you're of course aware, fixing
           | a Swiss watch with a sledgehammer will have a very low
           | success rate. The other end of the analogy spectrum could be
           | that it's a bit like a chemical catalyst. There's a lot of
           | resistance to a reaction happening on its own, but will very
           | likely happen if given the proper jolt.
        
             | wizzwizz4 wrote:
             | A better analogy might be "fixing a heart attack with your
             | fists". It _might_ work, if the problem is fibrillation or
             | a blocked artery and if the impact resolves it... or it
             | might just cause further injury without resolving anything.
             | (Or it might resolve the heart attack, but then cause a
             | stroke a few minutes later.)
        
           | earnesti wrote:
           | I agree, that taking psychedelics is likely not a good idea.
           | But the analogue gives in my opinion totally wrong picture of
           | the actual risks. Psychedelics, at least psilocybin, are
           | quite harmless compared to almost any other substances. The
           | reason for that is that they aren't very habit forming.
           | 
           | Personally I used psilocybin recreationally back in the days.
           | Got once bad experience and ended up in a psychosis and to
           | hospital. I got better in couple of days and long term
           | effects were nonexistent.
           | 
           | Then I have couple of friends whose basic substances are just
           | legal alcohol and cigarettes, and boy have they fucked their
           | lives with those. It just takes a long time to do it that but
           | psilocybin for sure does not lead to that kind of path.
        
           | phoronixrly wrote:
           | Thank you for the balanced opinion. It's a rarity here.
        
           | AnthonBerg wrote:
           | There is actually a ton of incredibly fascinating knowledge
           | about what psychedelics do - neuroimmunobiologically the
           | effects are profoundly interesting. It's a surprisingly sharp
           | and specific instrument, certainly double-edged though.
           | 
           | https://www.frontiersin.org/journals/immunology/articles/10..
           | ..
        
           | namaria wrote:
           | This isn't some erowid report. This is actually about studies
           | being made by professional researchers who are publishing
           | their results.
           | 
           | Evidence based medicine is always better than layman opinions
           | like 'psychedelics are a mental sledgehammer'.
        
           | jrflowers wrote:
           | Conversely, for some people trying to fix depression with
           | therapy and guided meditation can be a bit like trying to fix
           | a Swiss watch with therapy and guided meditation. Everybody
           | is different!
        
         | iancmceachern wrote:
         | Yeah, maybe don't take "very high doses". I've not done that.
         | And not had any seriously bad experiences. Maybe like
         | everything else is all about moderation?
        
           | DiscourseFan wrote:
           | It was 500ug of LSD mixed with probably 6 or 7 drinks of
           | alcohol. Suffered serotonin syndrome for a few days
           | afterwards.
           | 
           | Regardless I've heard stories of people having severe long
           | term psychological issues from even relatively light doses,
           | simply because of how their body in particular interacted
           | with the drug.
        
             | farts_mckensy wrote:
             | It's such a bad idea to combine alcohol with psychedelics.
             | You should lead off with exactly what you took so as not to
             | mislead others.
        
               | DiscourseFan wrote:
               | As I said my experience incurred more risk of severe long
               | term side effects, but those are possible in any
               | circumstance with any psychedelic with even a single, low
               | dose.
        
             | me551ah wrote:
             | 500ug of LSD isn't really a standard dose. It's almost
             | double your typical dose.
        
               | Galaxeblaffer wrote:
               | 250ug of good acid is still a very high dose! 500ug is
               | more like triple of a typical sane dose. milage may vary
               | i guess but 300ug sent me out of this world
        
               | Nesco wrote:
               | I know a guy who took 1000ug. He told me he had side
               | effects / visual glitches for about an entire week
        
               | notfed wrote:
               | According to Erowid, a "light" dose is 25ug-75ug, a
               | "standard" dose is 50ug-150ug, and a "heavy" dose is
               | 400ug+.
        
             | fluorinerocket wrote:
             | 500ug is nuts
        
             | AnthonBerg wrote:
             | Thank you for telling the story.
             | 
             | To me, it's interesting to consider the inflammatory
             | aspects - the immunomodulatory effects of LSD and other
             | psychedelics on one hand and alcohol on the other.
             | 
             | It's well established but little-known that psychedelics
             | have a very significant inflammation-reducing effect which
             | includes drastic reduction of neuroinflammation. (I'm
             | fairly sure that this is a primary reason why they work for
             | depression and anxiety; There's basically always elevated
             | inflammatory biomarkers with these disorders. Stress is
             | directly causative of neuroimflammation.)
             | 
             | Here's a really solid review paper from 2017 - today a lot
             | more knowledge has been accumulated: https://www.frontiersi
             | n.org/journals/immunology/articles/10....
             | 
             | Alcohol is known to be pro-inflammatory.
             | 
             | I have a hunch that these two disjoint forces on the same
             | physiological systems can have made things worse.
        
             | alemanek wrote:
             | That's a massive dose and you mixed it with alcohol. That
             | is in no way a responsible way to try out psychedelics. You
             | are right that everyone reacts differently which is why you
             | don't take a very large dose mixed with other drugs.
             | 
             | Anecdotally, ayuasca quite literally saved my life and
             | helped me tremendously when I was spiraling into a deep
             | depression. Psychedelics when taken responsibly in a
             | controlled environment under supervision can help a lot of
             | people.
        
             | AStonesThrow wrote:
             | > Suffered serotonin syndrome for a few days afterwards.
             | 
             | What sort of physician diagnosed you with Serotonin
             | Syndrome? What symptoms did you describe to them, and what
             | criteria/evidence did they use to arrive there? Were they
             | able to use differential diagnosis to rule out other
             | conditions?
             | 
             | Did you return to the same physician after the symptoms
             | ceased?
        
             | hmcq6 wrote:
             | You got serotonin syndrome from LSD?
             | 
             | That is incredibly rare, so rare I can't find any other
             | documented cases
             | 
             | Edit: did you test it to make sure it was real LSD?
        
               | Klonoar wrote:
               | I'm somewhat surprised there's only one comment here
               | asking this.
        
         | wnolens wrote:
         | Had a very similar experience. Took ~2y to fully go away.
        
         | farts_mckensy wrote:
         | I'm a little ambivalent about this response. It sounds like
         | you're describing invasive thoughts of some kind, though your
         | description is vague. At any rate, despite the perceived
         | negative effects, by your own account, it apparently spurred
         | you to lead a healthier life; in other contexts, this is
         | precisely the thing that is praised when it comes to
         | psilocybin.
        
           | DiscourseFan wrote:
           | > it apparently spurred you to lead a healthier life
           | 
           | No, I stopped mostly after I'd recovered. And I definitely
           | wasn't "healthier" then, just addled.
        
         | hackernewds wrote:
         | Did you take it in a controlled environment like the study
         | suggests? Every time serious conversation of medical progress
         | comes up, it's polluted by naysayers with anecdata about how
         | they took it while raving beside a live volcano.
         | 
         | We need to give psychedelics a fair chance, and sure after we
         | can discount them. The article suggests at scale there is
         | potential
        
           | phoronixrly wrote:
           | In my experience (this thread, too), the conversation gets
           | polluted by people that swear by their self-medication and
           | call more cautious people naysayers.
        
             | feoren wrote:
             | How come every time we try to have a conversion, it always
             | ends up all "point counterpoint" and "personal experience
             | with the topic" and "differing personal experience" and
             | "discussion of how those experiences relate to the topic"!?
             | EVERY TIME!
        
               | DiscourseFan wrote:
               | Its almost as if all experience is subjective...
        
               | phoronixrly wrote:
               | The only valuable conversation about such research is an
               | objective discussion of the quality of the study at hand.
        
               | worik wrote:
               | > The only valuable conversation about such research is
               | an objective discussion of the quality of the study at
               | hand.
               | 
               | No
               | 
               | People's lived experience is very useful
        
               | ants_everywhere wrote:
               | Those are called anecdotes.
               | 
               | Empirically, they're usually not nearly as useful as
               | people think. People are on average unreliable observers
               | of their own experiences.
               | 
               | Much better than individual anecdotes are collections of
               | anecdotes that are searchable and somewhat categorized. A
               | lot of old school drug forums provide this.
               | 
               | Much better still is systematically varying data and
               | taking statistics to separate signal from noise.
        
           | DiscourseFan wrote:
           | In the pre-modern world people had a very different
           | relationship to death and there wasn't anything like anxiety
           | as its experienced today. Psychedelics are essentially an
           | attempt to bring someone back to a more "authentic"
           | experience of life before technological controls settled in.
           | Perhaps its better to take the chance? I think so, but I want
           | others to recognize it as a genuine risk that is truly
           | unpredictable and not a personal failing on the part of the
           | user.
        
             | griffzhowl wrote:
             | I wonder what you mean by saying there wasn't anything like
             | anxiety as it's experienced today in the premodern world.
             | The term "anxiety" comes from Latin "anxietas", and Old
             | English had "angsumnes", both with apparently similar
             | meanings, so it seems the idea has been around for a while,
             | and most likely because it's a basic human emotional
             | condition that could occur in various circumstances
             | throughout history and prehistory.
             | 
             | As for a relationship to death, it's difficult to
             | generalise over all people throughout history, but for
             | example in medieval Europe where you had a seemingly quite
             | vivid belief in the possibility of hell after life, that
             | could result in some extreme anxiety of the most
             | inescapable kind. Maybe that accounts for some of the more
             | extreme behaviours of those times, who knows.
        
         | dimal wrote:
         | > we do not know, really, what goes on in there when you take a
         | drug like Psilocybin
         | 
         | FYI, same goes for SSRIs. The scientific consensus is that the
         | serotonin deficiency theory of depression was wrong. When SSRIs
         | actually work, we still don't know why.
         | 
         | I've had bad trips, too. Very bad, but I still think that
         | psilocybin (in a controlled, supportive setting) is a better
         | bet. My bad trips were all due to being in bad settings and
         | being completely unprepared for what could go wrong. I was
         | young and dumb and just fucking around. But tripping in
         | positive supportive settings was incredibly helpful. And if we
         | do find a way to do this right, then people don't have to take
         | drugs for the rest of their lives. Psychiatric drugs are
         | generally lifelong sentences, and negative side effects tend to
         | compound over time, which often leads to polypharmacy, and more
         | side effects.
        
           | DiscourseFan wrote:
           | I agree. But I don't think psychedelics are the end all be
           | all, that's all
        
           | Levitating wrote:
           | SSRIs barely work. For mild to moderate depression a placebo
           | works similarly or better. Only for severe cases of
           | depression are SSRIs found to be helpful because they
           | surpress all emotion.
        
             | grandpoobah wrote:
             | Worked great for me. Placebo might have worked too, but
             | doctors don't prescribe those!
        
             | drakonka wrote:
             | Maybe the effect is different when prescribed for something
             | other than depression, but I did not find my SSRI to
             | suppress my emotions. It simply helps me curb rumination
             | and negative thought spirals. Helps to feel "lighter" and
             | simultaneously more grounded. If anything, that allows me
             | to feel _more_ positive emotion rather than suppressing it.
        
               | hn_version_0023 wrote:
               | Cool, glad you had a positive experience. My experience
               | was the opposite: emotionally numb to the point where
               | awfully bad things happened in my presence and I barely
               | shrugged.
               | 
               | Being unable to feel joy or pain, being unable to cry
               | when a loved on passed on; these were the hallmarks of my
               | time on SSRIs. Never again will I subject myself to these
               | drugs.
               | 
               | It took me twice as long to get off them as I was on
               | them. Two years of prescribed meds, 4 years to get off
               | them. Six years of my life spent as a literal zombie
               | person.
               | 
               | We don't know why they work or don't. Our experiences are
               | just anecdata.
        
               | worik wrote:
               | > Our experiences are just anecdata.
               | 
               | Just?
               | 
               | Anecdotes matter
        
             | dymax78 wrote:
             | ~50% response rate for people with major depressive
             | disorder isn't "barely working" -- for millions of people,
             | SSRIs significantly improve their quality of life.
             | Unfortunately, there is no "one size fits all" solution and
             | often those of us with MDD have to try different
             | medications, in conjunction with a (good) therapist before
             | we find what works best.
             | 
             | Personally, I've run the gamut on SSRIs and they never
             | suppressed all emotion.
        
             | zdragnar wrote:
             | This is blatantly false. I've been on a few. Some didn't
             | help, some made me worse. The one I'm on now is extremely
             | helpful, and saved me.
             | 
             | None of them had any suppressant effects on my emotions at
             | all.
        
         | bugbuddy wrote:
         | > Ok like most of you I've taken psychedelic drugs.
         | 
         | I would like to see some actual data because my assumption has
         | always been that most people have never tried any. I personally
         | have not had any. I have always subscribed to the slippery
         | slope theory of vice.
        
           | DiscourseFan wrote:
           | Most people in this thread who are taking the position I'm
           | critiquing, then
        
           | worik wrote:
           | > I have always subscribed to the slippery slope theory of
           | vice
           | 
           | Me too
           | 
           | Come on over the skiing is great!
        
         | imwillofficial wrote:
         | "Like most of you"
         | 
         | "Objection, assuming facts not in evidence"
        
         | peepee1982 wrote:
         | Anyone who has ever tried to fine-tune medication for
         | psychological issues knows how challenging it can be to get the
         | dosages and combinations just right. In my experience, even
         | medications within the same class can have different effects on
         | different people, especially when combined with drugs from
         | other classes.
         | 
         | The interactions between medications, as well as the patient's
         | individual response, are hard to predict. These reactions can
         | change over time, too, as bodies and brains adapt, and
         | lifestyles shift.
         | 
         | Yet, you often hear oversimplified statements like "depression
         | means you have too little serotonin," "feeling sluggish means
         | you lack noradrenaline," or "difficulty focusing means you have
         | too little dopamine." These explanations are so reductive that
         | they barely make sense.
         | 
         | The more I read about drug trials, the more I realize how
         | little I -- and even many professionals -- truly understand
         | about how these medications work and the best way to make
         | informed treatment decisions.
        
         | washadjeffmad wrote:
         | I had a profoundly difficult trip that affected me deeply. It
         | felt eternal, and when I emerged, I could feel it in my head
         | like some antimemetic parasite that fed off disgust and terror.
         | I can still remember the feeling, twenty years later, if I try,
         | so I don't. I had to learn how not to be influenced by it, and
         | in doing so, learned about myself. And as I changed, because I
         | was aware of what I knew, I knew when I'd changed.
         | 
         | Our selves are not immutable, steady states. Our experiences
         | shape us. It's a lesson learned to guard that carefully and
         | jealously.
        
           | dingnuts wrote:
           | funny, I could have written the same post but about boring
           | old general anesthesia given before surgery
        
             | SoftTalker wrote:
             | How long ago?
             | 
             | Every general anesthesia I've had was basically "OK you'll
             | start to get sleepy now" and then "ok we're finished" and
             | zero awareness of any elapsed time.
        
               | johnmaguire wrote:
               | The paper here is worth a look:
               | https://news.ycombinator.com/item?id=36323275
               | 
               | Also this post has stuck with me through the years:
               | https://news.ycombinator.com/item?id=24566568
               | 
               | Be sure to scroll down to the comment thread started by
               | myself248.
        
         | brandall10 wrote:
         | Why did you take a very high dose?
         | 
         | As someone who was experienced with psilocybin some 20+ years
         | ago, I always took fairly consistent doses (roughly 3 grams),
         | as I could sense taking much more would be playing with fire.
         | This was pretty much a given amongst my circle of a dozen
         | friends who experienced these trips with me... hero doses were
         | almost never a good or healthy idea. Fun to read about on
         | Erowid though, mostly as cautionary tales.
         | 
         | My time with the substance ended after two bad trips (after a
         | few dozen great ones over a period of 5 years), but neither
         | produced any sort of even minor lasting effect.
        
           | appplication wrote:
           | > Why did you take a very high dose?
           | 
           | Hindsight is 20/20 but often it's not clear at the time if
           | it's a bad idea or how bad it can be. I think it's not such a
           | fair question to someone struggling to find effective
           | treatment for mental health issues to make a mistake on
           | dosing. Especially given both government and medical field
           | have historically not amenable to openly communicating harm
           | reduction or safe guidelines for experimentation with this
           | particular medicine.
        
         | jrflowers wrote:
         | For folks that are interested in anecdotes about psychedelics,
         | I recommend reading Erowid expertise vaults as what gets
         | volunteered here is very narrow and not representative of the
         | population as a whole.
         | 
         | I would know, as _my_ psychedelic mega dose stories are very
         | different from this and also completely unique to me.
         | 
         | I've done 500ug of LSD and it was great fun. I scheduled a day
         | off to rest ahead of time and was back to normal after that.
         | 
         | 250ug of LSD + 1 full ounce of golden teacher psilocybe
         | cubensis and had a somewhat spiritual experience, took a couple
         | days before I wanted to resume normal life.
         | 
         | + a dozen or more similar stories
         | 
         | There is a reason why "set and setting" is repeated so heavily
         | when instructing people on how to use these substances. Any
         | discussion of potential subjective benefits or harms of a
         | psychedelic in the context of an experience without specific
         | accounting for that is fundamentally incomplete.
         | 
         | That being said, if my experience sounds ridiculous to you,
         | that's because it's unique to me, just as others' are unique to
         | them. There isn't really much to be gained by talking about
         | individual experiences other than it's an entertaining topic of
         | discussion. It gets everybody exactly _nowhere_ closer to
         | establishing the objective clinical value of these things,
         | though.
        
           | sva_ wrote:
           | 'great fun' seems like a weird way to describe a 500ug trip.
           | Did you have some tolerance before this, and do you have very
           | high confidence that the dosage is accurate?
        
             | jrflowers wrote:
             | No tolerance, and yes the dosage was accurate.
             | 
             | I picked "great fun" as a description as a shorthand
             | because, while I could write more about it, it had little
             | to no net positive or negative impacts on my mental health.
             | For the purposes of this discussion, "Great fun" is kind of
             | meant to communicate that the story is neither a warning or
             | a recommendation regarding depression or any other mental
             | health condition.
        
         | rjbwork wrote:
         | >Thoughts came out of nowhere, I had no control over them;
         | often the constant, unceasing flow of thought was distressing
         | and uncomfortable.
         | 
         | I want to touch on this. "You" never have any control of your
         | thoughts, because "you" isn't really a thing. Psychedelics and
         | meditation teach us this if you pay close attention. The
         | thoughts arise from nowhere and we - the imagined, but illusory
         | - self are mere observers along for the ride that is
         | consciousness.
         | 
         | I can imagine that using a substance such a psilocybin could
         | cause your thought patterns to have both short and long term
         | changes in quality (in terms of substance, not of superior
         | gradation), however. It's also possible that your experience
         | led to your paying greater attention to the thoughts that did
         | arise, and over time the feedback loop of consciousness along
         | with taking better care of yourself led to greater moderation
         | of their genesis.
        
           | gmoot wrote:
           | "You" can learn to steer your mind by choosing which of these
           | thoughts to capture and dwell on, by monitoring them.
           | 
           | There is voluminous writing in the area of monastic
           | spiritually about this. On the one hand, they affirm that
           | these thoughts aren't chosen, using the vocabulary of sinful
           | thoughts introduced by demons. But it's also clear that
           | change is possible through prayer/meditation (not exactly
           | identical to modern ideas about mindfulness).
        
             | rjbwork wrote:
             | I tend to agree that change is possible and you can learn
             | to steer, but that too is no choice.
        
         | beardedwizard wrote:
         | This is a real risk I see overlooked and minimized often.
         | People should not assume it can't happen to them.
        
       | baxuz wrote:
       | What 2 decades of on & off therapies and meds couldn't fix, a
       | single psilocybin trip fixed in 5 hours. That's all the proof I
       | need.
       | 
       | Not even getting into the side-effects of SSRIs including PSSD,
       | brain zaps, lethargy, and a whole lot more.
       | 
       | I just don't understand people who do this shit recreationally,
       | as it was quite possibly the worst experience I had in my life.
        
         | jorgesborges wrote:
         | If you don't mind my asking, what about the experience was so
         | bad? Did it take time or work to process the experience for it
         | to have its beneficial effect?
        
           | baxuz wrote:
           | It's fine, I'm ok with sharing, although some of this might
           | sound gibberish as it's hard to explain. Note, that I am not
           | trying to impart any sort of mystical value to this, or
           | trying to be poetic.
           | 
           | It's an incredibly scary experience that makes you feel like
           | you're disintegrating in a metaphysical sense. Your mind,
           | perception, body. Yourself. Like you're falling apart, being
           | disassembled and that you will never be able to get yourself
           | together again. You have no agency. And then you are gone. I
           | believe this is what they call "ego death".
           | 
           | And then after you're gone, you're left with all these pieces
           | of yourself. Including a lot of them that you forgot ever
           | existed. Or how they fit together. Or some that you were
           | subconsciously aware of but never perceived them. Like
           | opening a shelf of Legos from your childhood. It's very
           | dream-like.
           | 
           | Then comes the awareness, understanding and grief. I've never
           | cried as much in my life, and I'm not a crying person.
           | 
           | Then comes hope.
           | 
           | And you get to assemble yourself back again. Feels like
           | something between waking up, coming back to reality and a
           | chain-reaction of those "AHA!" moments.
           | 
           | And then you're back, but you're not the same, and you
           | understand more about yourself.
           | 
           | While the next few months were some of the best I had in
           | decades, I'm extremely averse to repeating this experience,
           | as it feels really traumatic.
           | 
           | I was in a controlled, safe, although not a clinical
           | environment, and I am terribly aware how much this can fuck
           | your brain up in ways I can probably never imagine. We have
           | no idea how this machine works and this is basically
           | decompiling an incredibly complex binary during execution,
           | moving code around, recompiling, and hoping it works.
        
       | jtrn wrote:
       | This comment ignores the possible effectiveness of both
       | psilocybin and SSRIs and focuses on the usefulness of the
       | research itself. I actually believe that both have a role in
       | psychiatry, but this study tells me nothing with regards to
       | therapy.
       | 
       | Working as a clinical psychologist, who also reads a lot of
       | research, this study is just another brick in the wall that I am
       | banging my head against when it comes to doing actual evidence-
       | based therapy. I actually read the entire paper and the pre-
       | registration. The title on Medscape and the article are, to me,
       | completely reading the research wrong, and just another example
       | of the actual research design and findings living in a different
       | universe than the press release and subsequent discussion.
       | 
       | Let me try to communicate why I feel this way by summarizing the
       | research in my way, as opposed to the title: "Psilocybin Bests
       | SSRI for Major Depression in First Long-Term Comparison."
       | 
       | Hers my take: Research finds no significant difference between
       | psilocybin and SSRI in the primary outcome from pre-registration
       | (self-reported depression on an emailed form), even when only
       | administering SSRI for 6 weeks, where the maximum effect of SSRI
       | is expected at 12 weeks. As such, this does not even qualify as
       | standard treatment with SSRI. This is after excluding 90% of the
       | applicants for the study. The effectiveness is primary supported
       | by p-hacking, as seen by reporting additional measures not in the
       | registered, where some of them favor psilocybin. And SSRI
       | actually scores BETTER in the main outcome.
       | 
       | Now, someone might come along and call me cynical, mistaken, or
       | worse. But having been through this with biofeedback,
       | metacognitive therapy, light therapy, mindfulness therapy, and
       | ketamine treatment already, I can clearly see the same pattern:
       | lying by omission, p-hacking, not taking into account the
       | "decline effect," borderline acceptable results. It all
       | culminates in a big nothingburger, and any progress for my field
       | remains stagnant. Based on the quality of this study, I am
       | certain that if we just aggressively started treating depression
       | with psilocybin, I just know that it wouldn't make much
       | difference, because I have been through it before with the exact
       | same numbers and effect sizes, just different treatment
       | modalities.
       | 
       | Here is the best indication I found for SSRI: Resistant phobic
       | anxiety (panic attacks that don't stop even after long exposure),
       | and burnout-related depression (person worked normally their
       | whole life but is suddenly just empty of energy and does not look
       | forward to anything with joy). These are examples that very often
       | make a big difference with SSRI, in conjunction with therapy.
       | 
       | Psilocybin seems to work best for existential depression and
       | anxiety that is driven by pathological self-focus (not egotism,
       | but inability to stop focusing on one's own inner states).
       | 
       | But these personal theories are just that, and the studies that
       | keep getting funding are very seldom useful, at least for me, as
       | I genuinely am trying my best to help my patients.
        
         | zozbot234 wrote:
         | > ... burnout-related depression (person worked normally their
         | whole life but is suddenly just empty of energy and does not
         | look forward to anything with joy) ... existential depression
         | and anxiety that is driven by pathological self-focus (not
         | egotism, but inability to stop focusing on one's own inner
         | states)
         | 
         | Is there any rigorous operationalization of these concepts,
         | that might be explored in further studies? Unless one can be
         | found, these fuzzy, heavily qualitative descriptions are
         | unlikely to be helpful for future researchers.
        
           | jtrn wrote:
           | It's counterintuitive to me that a more specific
           | concept/subgroup of a phenomenon would be less useful than a
           | larger catch-all category. Is the self-rated questionnaire
           | depression scale used in this study a good "rigorously
           | operationalized concept"?
           | 
           | We are successfully treating people with this exact kind of
           | indication/operationalization with real success already. For
           | instance, the indication criteria for ECT basically follow
           | the "burnout profile" I described above, with the addition of
           | "treatment resistant to therapy and medication," and it has
           | shown by far the best effectiveness for that kind of
           | depression.
           | 
           | I completely disagree that it's not possible to
           | operationalize the concepts above, for instance with standard
           | BDI or MADRS, supplemented with a ratio with a cutoff to
           | indicate a large fall in everyday functioning. Like an
           | extremely large fall in Global Functioning Scale (GAF)
           | localized to a distinct and pattern-breaking period in a
           | person's life. If you think that these concepts are fuzzy and
           | qualitative, I really hope you have even greater criticism
           | towards this study, not to speak of concepts like anxiety,
           | trauma, and ADHD, which are completely off the rails when it
           | comes to diffuseness and subjectivity.
           | 
           | But even if you are right, that burnout-depression and
           | existential anxiety are not possible to study because of
           | their vagueness, it still would not make this study helpful
           | as it's presented. Or am I mistaken? Do you think it's a good
           | and helpful study, whose implications I should fight for in
           | our clinic? And would I see a marked improvement in our
           | patients, compared to SSRIs for the "Depression" group?
           | 
           | I am willing to admit I am wrong. The only goal is to
           | actually help people.
        
         | krzat wrote:
         | Psychiatry seems to be very symptom based, depression is an
         | umbrella term for many completely different problems that show
         | as "big sad".
         | 
         | Maybe it would be more productive to base diagnosis on some
         | kind of brain imaging.
        
       | modeless wrote:
       | Bad headline. Psilocybin was not significantly different for
       | depression symptoms. Also there was no control group. Confidence
       | intervals were very large. Yet another unconvincing study with
       | bad journalism.
        
       | el_nahual wrote:
       | Will add a personal anecdote on my mental-health journey and the
       | impact psylocibin has had on my life.
       | 
       | Bio:
       | 
       | - Late 30s.
       | 
       | - Long history of depression my entire life. "Melancholic" child.
       | Bad drunk teenager. Suicidal in college (failed attempt).
       | 
       | - No drugs except alcohol until I was in my mid 20s.
       | 
       | I've been prone to major bouts of depression my entire life. I
       | went to therapy multiple times a week for years and got on SSRI's
       | towards the end of university as a response to a failed (but
       | serious) suicide attempt.
       | 
       | SSRI's never did anything for me except make me feel like shit
       | (and not be able to take one). Eventually I went off them and
       | sort of got by, and I managed to stay safe by drinking no
       | alcohol. Therapy twice a week was an utter waste of time and
       | money.
       | 
       | Then, sort of on a whim, I grew some mushrooms at home with my
       | then fiancee and we took them together. I was mid 20s and had no
       | prior experience with any drug but alcohol. Not knowing what I
       | was doing, we took a BIG dose. I had a trip that was fun at first
       | and then became quite unenjoyable.
       | 
       | For the next twelve months I felt like myself again. The change
       | was subtle but, over a long term, quite obvious.
       | 
       | After about 18 to 24 months, my depression came back. We took
       | mushrooms again and the same thing happened. A year of well being
       | in exhcange for 2 fun hours and 6 tough ones.
       | 
       | So about every two years I'll take a big (2-4g dry) dose of
       | mushrooms and...it's like magic. I feel like myself again. I'm
       | "back." Life is not happy, none of my problems go away, but I
       | feel like I'm an agent in my own life as opposed to a spectator.
       | 
       | The well being lasts about a year or 18 months (less if I've been
       | drinking alcohol). It's almost never as bad as when I was
       | suicidal, but it still sucks. For me depression is like being a
       | professional chef and one day your taste buds make everything
       | taste like ash. Or a painter and one day you see colors less and
       | less.
       | 
       | Last year I went into a VERY deep depression, so deep that I
       | _refused_ to take mushrooms until my wife basically forced me to.
       | Same thing. The very next day I felt like  "I was back."
       | 
       | Those things changed my life.
       | 
       | I've since had fun with other drugs maybe 5 times. Acid a couple
       | times, molly a couple times. Cheap (wtf) fun for a half a day,
       | but nothing like the impact mushrooms have on my mind.
       | 
       | I've had one bad trip while taking mushrooms recreationally. I
       | don't understand who would take those things for fun, at night.
       | 
       | Strictly during the day, well-rested, with loved ones, and in
       | nature!
       | 
       | I'm also convinced that the impact they have on me is purely
       | chemical. It has nothing to do with "facing my demons" or
       | "connecting with a higher spirit" or anything like that. I just
       | get off my stupid rut.
       | 
       | "Neurons that fire together wire together" as they say, and when
       | I'm depressed it's the stupid neurons that fire together.
       | Mushrooms makes a whole different set fire, and fire hard, and
       | that seems to be enough.
       | 
       | The deepeest lesson I've gotten while on shrooms is:
       | 
       | "I'm trying my best. Everything is actually fine."
       | 
       | Pretty good lesson.
        
       | Grandeculio wrote:
       | No shit.
        
       | debacle wrote:
       | I have been taking seratonin precursors (5-HTP, a supplement) for
       | about 4 months at a very low dosage (.3 of the "normal dose").
       | 
       | My chronic depression is mostly gone, but I have noticed an
       | uptick in physiological signs of anxiety (though no mental
       | signs).
       | 
       | But more importantly, my gut health is better than it has been in
       | 12 years. I am eating more and losing weight. My energy levels
       | have skyrocketed. My impulsiveness has catered so hard that I was
       | worried my libido was impacted. My executive function issues and
       | ADHD are greatly minimized.
       | 
       | All from a supplement. Utterly life changing.
        
         | Ey7NFZ3P0nzAe wrote:
         | Good for you. I'll just add that there is a non zero chance
         | that getting checked out or mentionning at least to your closed
         | ones about what you noticed would be a net benefit in plausible
         | futures, as thyroid issues, bipolar disorder, various
         | endocrinoloical disorders etc could also cause what you
         | perceive as benefits.
        
       | photochemsyn wrote:
       | Full research article:
       | 
       | https://www.thelancet.com/action/showPdf?pii=S2589-5370%2824...
       | 
       | Study design and methods:
       | 
       | > "All the patients provided written informed consent and after
       | discontinuing any pre-trial antidepressants, enrollees received
       | two oral doses of psilocybin (1 mg or 25 mg) with accompaniment
       | from two experienced therapists for ~6-8 h, separated by 3 weeks,
       | as well as daily pills (escitalopram 10-20 mg or placebo
       | capsules). Thirty patients were randomised to PT and 29 to ET."
       | 
       | > 'The PT condition consisted of two high-dose (25 mg) treatment
       | sessions with the serotonergic psychedelic psilocybin,
       | administered with support from two study therapists...and daily
       | placebo capsules. The ET condition consisted of daily doses of
       | the selective serotonin reuptake inhibitor (SSRI) escitalopram -
       | 10 mg for three weeks followed by 20 mg for a further three weeks
       | --as well as equivalent psychological support including dosing
       | sessions with placebo-like doses of psilocybin (1 mg)."
       | 
       | This is an interesting way to address the placebo issue, giving a
       | noticeable microdose of psilocybin (1 mg) versus the active dose
       | (25 mg) for the non-control group.
       | 
       | Fundamentally I think psilocybin's main overall psychological
       | effect is to push subconscious issues up into the mind's
       | conscious processing space. Large doses can generate visual
       | hallucinations related to those subconscious issues which can be
       | unpleasant, even terrifying, for many people, so that's why
       | caution is warranted. Extremely large doses cause complete
       | dissociation from external sensory input, which is of course very
       | dangerous for the unprepared individual in an uncontrolled
       | situation - an experience unlikely for any herbivore to want to
       | repeat, hence the evolutionary selection pressure for
       | biosynthesis of such compounds by plants and fungi.
        
       | thegrim33 wrote:
       | The results are based on a grand total of 25 people in the
       | psilocybin group and 21 people in the SSRI group. The sample size
       | is pretty small.
       | 
       | The methodology is also kind of strange, the psilocybin group got
       | a total of 20 hours of in-person therapy during their 'treatment'
       | and 6 follow-up skype calls, whereas the SSRI didn't get anything
       | other than the 6 month questionaire. Those 20 hours of
       | personalized therapy while they were dosing had no effect on
       | their psychology? Any change was all a result of the psilocybin
       | and not the 20 hours of therapy?
       | 
       | They also measured results by a self-administered 16 question
       | "quick inventory" depression survey. To enter the study they had
       | to be officially diagnosed with major depression by a doctor, but
       | the results of the study were based completely around a self-
       | reported 16 question questionaire?
        
         | notfed wrote:
         | If that's true, I'm confused how this is a "double-blind,
         | randomized, controlled trial"?
         | 
         | Also, what's up with drug studies always having such a low
         | sample size? Is it really that hard to find people who'd
         | volunteer to get free drugs?
        
           | Affric wrote:
           | Often you're not allowed on your medication for any of your
           | other health issues.
        
             | londons_explore wrote:
             | We need a new approach to randomly controlled trials.
             | 
             | I propose a new approach: Rather than given treatment vs
             | not given treatment, we instead vary the dose _slightly_ ,
             | and we include the whole world in the trial.
             | 
             | Ie. instead of taking 100mg of Advil, instead you will
             | receive somewhere between 95mg and 105mg of Advil. You
             | won't be told how much you got - but the barcode on the box
             | will encode that info. That already might be the case due
             | to allowed inaccuracies, but now we're gonna measure and
             | record it.
             | 
             | Later, the data of which box was dispensed is combined with
             | any other relevant medical records, and across the hundreds
             | of millions of people involved, any benefit/disadvantage of
             | a small increase or decrease in dose will become apparent.
        
               | refulgentis wrote:
               | This doesn't sound very helpful
        
               | malfist wrote:
               | That's not generally how drugs work. There's wide margins
               | on how much dose is required for clinically significant
               | results. Not only is the 110 pouns petite woman taking
               | the same dose of aspirin as a 400lb elite powerlifter,
               | but the effects can't be quantified in high resolution.
               | The woman can't say her pain was 5% less than the
               | powerlifter, and they can't say their pain was 5% more.
        
           | andoando wrote:
           | Its expensive. Statistically speaking its really not that
           | small. You can always argue p hacking but these are always
           | useful as a means to do further research
        
         | napoleongl wrote:
         | The article states that both groups received psychological
         | support though. The only mention of 20 hours I find in the
         | article is as an option to psilocybin. Does the original
         | research article say something else?
        
         | luckydata wrote:
         | Therapy is such a wash statistically that I'm not particularly
         | confused or concerned by that, and everyone that has ever taken
         | psylocibin knows the results are typical.
        
           | arcticbull wrote:
           | It's kinda interesting you say that because studies show that
           | SSRIs are not much better than placebo for treating
           | depression, and that therapy plus SSRIs is the best treatment
           | available right now.
           | 
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592645/
        
         | fsckboy wrote:
         | > _The results are based on a grand total of 25 people in the
         | psilocybin group and 21 people in the SSRI group._
         | 
         | Statistical significance is based on sample size, and is
         | independent of population size. Let that sink in, doesn't
         | matter if your population is 100K or 8 billion, when you sample
         | you are trying to understand the probabilities in your sample,
         | not in the population.
         | 
         | Therefore, (think about the birthday paradox, doesn't matter
         | how many people in the world, a few dozen in the room with you
         | is an adequate sample), it should not surprise you that
         | statistical significance is achieved through a much smaller
         | sample size than most non-statisticians have intuition for.
        
           | seeknotfind wrote:
           | The issue your parent comment raises is that this random
           | group may not represent someone that's trying to evaluate
           | what techniques can help them, regardless of the statistical
           | significance within that group. It makes me sad that they
           | introduce other random variables, as incontrovertible
           | evidence of efficacy could help a lot of people!
        
       | shadowtree wrote:
       | Ah, but does it beat exercise, fresh air and sunlight?
       | 
       | https://www.mayoclinic.org/diseases-conditions/depression/in...
        
       | Molitor5901 wrote:
       | Very much related. Many people are getting shrooms through
       | establishments selling it in the form of chocolate. However it is
       | apparent that much of that is adulterated and synthetic.
       | 
       | https://news.ycombinator.com/item?id=41283493
        
       | xterminator wrote:
       | Psychedelics are nice and powerful - maybe too powerful. I don't
       | trust the system to use them responsibly. I'd rather obtain and
       | use them on my own than as part of some private - or governmental
       | - initiative. There's no one to trust more than a good friend to
       | be there for you when the ride gets bumpy, not some guy in a suit
       | doing it for the money.
        
         | throwup238 wrote:
         | Thankfully it's just mushrooms. It must be one of the easiest
         | drugs to grow yourself after just dropping a cannabis seed in
         | the ground. As long as spores are accessible it'll be
         | "democratized" and even in places like California where they're
         | illegal to ship, they're still easy to get.
         | 
         | It's a lot harder to accurately dose in its natural form
         | though.
        
         | the_gorilla wrote:
         | As an outside observer, I have to notice that doctors and "the
         | system" have lost such trust that people prefer self-medicating
         | with illegal drugs.
        
           | SoftTalker wrote:
           | "The system" has no interest in curing your depression. They
           | want you to keep making therapy appointments, and they want
           | you to keep refilling prescriptions.
           | 
           | Individual doctors may or may not have this view. I'm talking
           | about "the system." Just consider the incentives. That tells
           | you all you need to know.
        
             | Sharlin wrote:
             | When "the system" subsidizes your therapy and your
             | prescription drugs (as in most civilized societies), and
             | indeed pays for your medical leave and loses value in the
             | form of lost workdays, it definitely doesn't have much of
             | an incentive to keep you in therapy or on drugs.
        
               | iknowSFR wrote:
               | I get the impression that there's misalignment on what
               | "the system" is to each commenter here. One side views it
               | as the larger society and the other as the pharmaceutical
               | industry.
        
             | lovethevoid wrote:
             | I don't think you've really considered the incentives
             | either.
             | 
             | The system has as much interest in curing your depression
             | as it does curing obesity. Long term, these conditions are
             | very costly. It takes people out of peak condition, reduces
             | labor pool, increases number of patients taking up
             | resources at hospitals and doctors offices, and so on. A
             | system which encourages these things is a failing one, as
             | taxpayer costs would only continue to balloon.
             | 
             | Additionally, since the thread is about psilocybin, people
             | would still be filling up prescriptions for those.
             | 
             | Also, self-medicating is also very costly. Not only to the
             | system, as people often wind up in hospitals due to laced
             | products or incorrect doses (see marijuana in a lot of
             | states where dealers really aren't concerned about
             | quality), but also to the individual. People are spending
             | absurd amounts of money on vitamins and mushroom teas and
             | all that in hopes it helps, but rarely is that the case due
             | to these categories not being strictly regulated.
        
           | detourdog wrote:
           | I think the advertising of pharmaceutical is big loss of
           | faith. Not to mention the opioid crisis.
           | 
           | If medicine was an honorable industry in the USA the might be
           | more faith.
        
         | crazygringo wrote:
         | > _There 's no one to trust more than a good friend to be there
         | for you when the ride gets bumpy, not some guy in a suit doing
         | it for the money._
         | 
         | I couldn't disagree more.
         | 
         | Your good friend most likely doesn't have the slightest idea
         | how to handle things if your trip goes south. Especially when
         | they're on their own "ride". That's not to disparage anyone,
         | but just to state the fact that there is training around these
         | things that comes from lots of experience.
         | 
         | And therapists are not "some guy in a suit doing it for the
         | money". You don't get rich doing psychotherapy -- you do it
         | because you genuinely want to help people. And never in my life
         | have I seen a therapist in a suit.
         | 
         | This isn't to say that every therapist is great or that every
         | friend is terrible -- just that the relative success rates of
         | being able to help someone on a bad trip, both during and
         | after, are going to be a lot higher on the side of trained
         | therapists. Because of the training.
        
           | xterminator wrote:
           | >Your good friend most likely doesn't have the slightest idea
           | how to handle things if your trip goes south.
           | 
           | Yes they can, everyone experienced can. It's part of having
           | empathy.
           | 
           | >Especially when they're on their own "ride".
           | 
           | The trip sitter doesn't trip while sitting.
        
       | anonymouse3112 wrote:
       | Anecdotally: worked for me, would absolutely do it again.
       | 
       | People worry about various side-effects: I work extremely hard
       | and know others who have done psychedelics and continue with b2b
       | saas and similar.
       | 
       | That said, it's serious stuff. I think it permanently increased
       | the amount that I like music; other studies show longtitudinal
       | changes to big-five personality traits. Proceed with caution.
        
         | sedatk wrote:
         | How do you even go about proper dosing and frequency of
         | psilocybin use? Just random guess?
        
           | snek_case wrote:
           | You can look at studies done using psylocybin for a start,
           | but also, adjust based on your own experience. Most people
           | use between one and two grams of mushrooms, with two grams
           | being quite strong strong for many people.
           | 
           | Some people are tempted to push the dosage so far as they can
           | take it to experience "ego death", and I don't think that's
           | necessary for therapeutic effects. Not quite sure how safe it
           | is to push the dosage as high as you can either. There's some
           | kind of esoteric belief in some circles that you'll get some
           | magic enlightenment, connecting with another realm if you
           | trip hard enough, but imo that mostly attracts people who
           | already have fragile mental health.
        
           | staticvoidstar wrote:
           | Not totally random, but yeah it's kind of a crap shoot. But
           | to be fair it's no different than a lot of other
           | pharmaceuticals where it's just trial and error until you
           | figure out what works for you.
           | 
           | So like pharmaceuticals, you figure out your goals, go with
           | something in the range that works for most people. It doesn't
           | hurt to start very small (0.25g), which some people do every
           | day. There's a lot of variables including strains and even
           | when/what you ate last, where you are in any kind of hormone
           | swing (men have them too), so trial and error is about as
           | best we can get for now (recreationally). This is why I'm
           | really excited by these new pharmaceuticals.
        
           | wisemang wrote:
           | Anecdotal but whenever I've been asked for this guidance
           | (having been around the block, but not a shaman by any means)
           | I ask about the person's dreams. Do they usually remember
           | them, how intense are they? More intense = start with lower
           | dose (maybe .5g). Less so maybe start with 1 or 1.5g. Of
           | course this is subjective and relative but a rule of thumb
           | that has worked reasonably well.
           | 
           | For frequency, that depends on a variety of factors I
           | suppose.
        
       | pessimizer wrote:
       | From what I recall, SSRIs only show an effect greater than
       | placebo in major depression, and that effect goes away if the
       | placebo is active (i.e. the placebo makes you a little sick, so
       | you can "feel it working.")
       | 
       | Great idea to compare a new trendy treatment with promise of
       | potential financial windfalls to another treatment that barely
       | works. If you kept feeding them cocaine under medical
       | supervision, they'd probably report feeling slightly better, too.
       | They're recreational drugs. People take them because they feel
       | good. The most common symptom of depression is to take refuge in
       | drug consumption.
        
       | black_puppydog wrote:
       | Lol, I opened this in a tab in background and until I
       | foregrounded the tab it reloaded every 2 seconds or so. I hate
       | the modern web... :)
        
       | AI_beffr wrote:
       | in 2020 i was very interested in psychedelics because of the
       | breakthrough with PTSD and MDMA via MAPS. so i read pihkal and
       | tihkal and i started reading a biochemistry textbook and
       | generally took an intense interest in that area. and i went to
       | oakland when i had the chance to be back in the bay area and i
       | went to zide door and bought a small amount of psilocybin. at a
       | bohemian friends house (it has since been cleaned out and sold,
       | perhaps the last such house in the bay area at the time!) i took
       | the little capsule in my palm and contemplated if i really wanted
       | to take the risk. and i did. it was not a large enough dose to
       | produce a psychoactive effect -- i think i had read that a
       | psychoactive dose was not necessary to see benefits in mental
       | health. there is one effect that i remember very clearly. it was
       | when it got later into the night that i noticed something subtle
       | but extremely strange. i felt awake or energized in some way. and
       | i realized that my whole life, during the evening and late hours
       | i would be sort of depressed and not feeling good. and so that
       | was the first time that i felt lucid and energized after dusk. my
       | whole life i had always known that i feel very depressed and
       | agitated at dusk. but this experience really showed me how
       | abnormal it was. later on i made a connection that is very oddly
       | absent in medical circles that explains this. you know how when
       | someone is having a deadly allergic reaction they are meant to
       | use what is known as an "epi-pen?" thats because epinephrine,
       | whats inside the pen, reduces inflammation. but what isnt
       | mentioned or connected anywhere to anything is that when you go
       | to sleep at night your body massively reduces the level of
       | epinephrine that circulates in your blood so that you can sleep.
       | inflammation therefore must increase. and inflammation is
       | implicated in many psychiatric disorders including and perhaps
       | most of all with depression.
       | 
       | one time much later i was in the hospital because i had a bad
       | fever. maybe i was being kind of paranoid for going in. but as i
       | was laying in the hospital bed my fever suddenly broke. and a
       | wave of intense depression, unmistakable, washed over me. i
       | thought this might be turning into an emergency but soon enough
       | it passed as if nothing had happened. it was very useful to know
       | about the connection between inflammation and depression during
       | that little journey.
       | 
       | why is the connection between inflammation and various
       | psychiatric diseases not taken seriously by the medical
       | establishment? because its too complicated of a subsystem for a
       | statistical study to tease it out. even if it were the sole cause
       | of depression it still wouldnt lend itself to any study that is
       | not exploring directly the biochemical mechanism. expect some
       | breakthroughs in this area.
        
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