24 ms·

Psilocybin bests SSRI for major depression in first long-term comparison

582 points by Thomvis 2y ago

EGreg 2y ago
Didnt a lot of studies finally come out by 2022 showing that SSRIs are not actually effective for most people, no more than a placebo? And the whole link between serotonin and depression was spurious… 2021: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2776611 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/... 2022: https://www.jwatch.org/na55225/2022/08/16/antidepressants-work-only-small-subset-patients https://www.jwatch.org/na55225/2022/08/16/antidepressants-wo... 2023: https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0 In any case, I believe that ADHD, Depression and many other “umbrella” psychiatric diagnoses are being overdiagnosed, much like “hysteria” was for hundreds of years (eg 1 in 4 middle-aged women is on antidepressants now, and the opioid epidemic in men was largely exacerbated by the pharma industry, as has the overdiagnosis of ADHD prescribing amphetamines to kids). To be fair, the actual incidence of phychiatric conditions from ADHD to autism to depression has increased, as well as autoimmune disorders, diabetes etc. although not as much as the pharma industry wants us to believe. It could very well be the result of upstream changes in nutrition (eg wild increases in sugars like fructose across the board, antibiotic overuse on factory farms, buildup of microplastics everywhere etc.), and to a large degree society (including loneliness, dating, relationships, work, etc) and medicating them downstream (eg with amphetamines or opioids) is just a bandaid. Late stage capitalism has had a direct role in exacerbating this. For example, the tech industry (which many on HN are involved in) has redefined dating, relationships, job searches, political discourse, and much more. All of these affect how people interact. A seminal book even back in 2001 was “Bowling Alone” by Robert Putnam, who noticed Americans aren’t attending communal activities like they used to. Corporations have co-opted many movements (like women’s lib) to make people work harder, neglect their kids, eat unhealthy food, become obese, develop diabetes, lose sleep, and now be part of the gig economy etc. I like to show this Cadillac commercial from 2014 as a great example of the corporate brainwashing: https://www.youtube.com/watch?v=xNzXze5Yza8 https://www.youtube.com/watch?v=xNzXze5Yza8
- seec 2y ago
  Yeah that's just society absolutely wants to label/categorize behavior that appear to fall outside of the normal, most of the time failing to understand that those behavior have roots in the genetic makeup of the person as well as his personal experience. Most of the time there is nothing really wrong with the diagnosed perso but capitalist/productive society push for normalized behavior so that individuals have less difference and more exploitable/interchangeable. Funny thing is that you can make the arguments that many of those behaviors are actually adaptation to the environment and may sometimes be the future of humanity. That do not please the productivistes who want to extract as much value of every individual as possible, like we do with cattle. Now they are some very crazy people out there but it's a very small part of the population and you can often trace the problem back to genetics or physical impairement (environmental or else). Solving that sort of thing with drugs or therapy is basically wishful thinking, but it makes money so I guess that's ok... As far as I can tell the whole field of psychology/psychiatry is basically just one step removed from full on charlatanism. We can learn some stuff about people's behavior, take some moral judgment about what's good or not (changes with time as well as political viewpoint) but the drive to specifically categorize is a bit crazy in itself...
  - neom 2y ago
    I read a bunch of your comments. For someone who has no idea what they're talking about you sure hold some dangerously belief. I'd strongly advise people to ignore folks who are clearly not experienced in something they profess to know about.
    - EGreg 2y ago
      What I said is factually-based The person who replied to me I think blew it out of proportion, and went beyond what is supported by facts While you may be right to caution people against the more reckless positions, I wish you’d also engage with what I actually said. Because the various industries thrive on exactly all of us policing each other and cautioning to not question all the convenient assumptions they are relying on us to perpetuate, to prop up the system.
jtrn 2y ago
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.
newsclues 2y ago
Taking LSD every few months was the best antidepressant I’ve ever tried and I’ve tried a bunch
- drcongo 2y ago
  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 2y ago
    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 2y ago
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 2y ago
  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.
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  - mtlmtlmtlmtl 2y ago
    Purely out of curiosity, which drug is this, if you don't mind me asking?
    - tootie 2y ago
      Sodium oxybate. Active ingredient is GHB. I was stunned to find out this was a therapeutic but apparently it was developed for potential therapies and was only coincidentally discovered to be intoxicating. I used to suffer debilitating cataplexy and sodium oxybate has nearly wiped it out.
      - mtlmtlmtlmtl 2y ago
        Right, GHB is an interesting one. It's always fascinated me how most recreational drugs are a wonderdrug for at least one medical condition. There are a couple of exceptions of course. Like synthetic cannabinoids. But even ethanol can be used as an antidote for methanol poisoning. For me it's amphetamine. I have severe dehabilitating ADHD-C and lisdexamphetamine has completely changed my life.
- pier25 2y ago
ValentinA23 2y ago
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor#Sexual_dysfunction 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/ https://www.pssdnetwork.org/ At least, the mushroom didn't steal my mojo
- cpucycling7 2y ago
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- bitcurious 2y ago
  Can psilocybin restore the mojo, or are you just commenting on the downside of SSRIs?
  - erie 2y ago
    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 2y ago
      happy ending?
cpucycling7 2y ago
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 2y ago
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/ 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 2y ago
  > 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 2y ago
  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 2y ago
    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-ketamine-placebo https://www.astralcodexten.com/p/does-anaesthesia-prove-keta...
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- BugsJustFindMe 2y ago
  > 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.
stefantalpalaru 2y ago
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dillydogg 2y ago
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 2y ago
  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 2y ago
    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 2y ago
  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 2y ago
  The doses of psilocybin being used were so low as to be barely perceptible.
deleted 2y ago
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jdietrich 2y ago
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 2y ago
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.
- rainclouds 2y ago
  Psilocybin has always made me not want to drink for extended periods of time after use. Always saw that as a great benefit.
- agumonkey 2y ago
  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 2y ago
    Psilocybin tolerance starts building immediately. Even if you microdose (100 mg), it will stop being effective after 3-4 days.
    - vlabakje90 2y ago
      100mg psilocybin is several times a heroic dose, but 100ug is far below a microdose. Do you mean 100mg of dried mushrooms?
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      - dymk 2y ago
        I think he means 100mg of mushroom body, which might be 1-2mg of psilocybin.
    - dymk 2y ago
      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.
8b16380d 2y ago
Funny, psilocybin has been largely detrimental to the mental health of everyone I know.
- api 2y ago
  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_ 2y ago
  my experience has been very different for everyone I know
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- joemazerino 2y ago
  Agreed with a caveat: SSRIs and other antidepressants are far worse.
- giantg2 2y ago
  "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 2y ago
  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 2y ago
    Thoughts on Mescaline/Peyote?
state_less 2y ago
> "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 2y ago
  > 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 2y ago
    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 2y ago
      The best thing to do is to consult with a physician on matters related to your health.
      - Wytwwww 2y ago
        Why? I mean it certainly depends but as far non severe mental health issues go physicians are just going to checklists since there is hardly anything else they can do (besides long-term therapy).
keepamovin 2y ago
But no patent, so this is "misinformation" haha
chiefalchemist 2y ago
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/ https://michaelpollan.com/books/how-to-change-your-mind/
sub7 2y ago
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 2y ago
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 2y ago
  You could compare against other psychedelics. I’d be interested in that.
  - zozbot234 2y ago
    You could also test it on severely sleep-deprived experimenters undergoing sensory isolation, but that would never get IRB approval.
    - roywiggins 2y ago
      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/september/sleep-deprivation-is-an-effective-antidepressant-for-nearly-half-of-depressed-patients https://www.pennmedicine.org/news/news-releases/2017/septemb...
  - cubefox 2y ago
    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.
iluvcommunism 2y ago
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 2y ago
  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 2y ago
    And it's mostly not legally acquired fentanyl that's killing people.
    - deleted 2y ago
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lumb63 2y ago
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 2y ago
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 2y ago
  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 2y ago
    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 2y ago
      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.)
_iaoo 2y ago
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 2y ago
  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?
  - _iaoo 2y ago
    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.
modeless 2y ago
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 2y ago
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 fiancée 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 2y ago
No shit.
debacle 2y ago
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 2y ago
  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 2y ago
Full research article: https://www.thelancet.com/action/showPdf?pii=S2589-5370%2824%2900378-X 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.
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thegrim33 2y ago
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 2y ago
  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 2y ago
    Often you’re not allowed on your medication for any of your other health issues.
    - londons_explore 2y ago
      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.
shadowtree 2y ago
Ah, but does it beat exercise, fresh air and sunlight? https://www.mayoclinic.org/diseases-conditions/depression/in-depth/depression-and-exercise/art-20046495 https://www.mayoclinic.org/diseases-conditions/depression/in...
Molitor5901 2y ago
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 https://news.ycombinator.com/item?id=41283493
xterminator 2y ago
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 2y ago
  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 2y ago
  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 2y ago
    "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 2y ago
      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 2y ago
anonymouse3112 2y ago
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 2y ago
  How do you even go about proper dosing and frequency of psilocybin use? Just random guess?
  - snek_case 2y ago
    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 2y ago
    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 2y ago
pessimizer 2y ago
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 2y ago
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 2y ago
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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ein0p 2y ago
I’m pretty sure getting repeatedly punched in the head would “best SSRIs” in a long term comparison too. Hasn’t the entire body of research that gave us SSRIs been exposed as fraud a couple of years ago?
torginus 2y ago
I have a theory that the medical community has a somewhat antagonistic view on mind-affecting drugs that work and have genuine positive effects - it's that healthy and/or undiagnosed people will take said drugs willingly, as they provide their positive effects for healthy individuals, and they'll instantly get labeled as abusable drugs, whose consumption is tied to heavy criminal charges. This reputation and the accompanying legal red tape makes medical research into said compounds very difficult. An ironclad rule for medically approved drugs is that no fun is allowed - approved drugs must not have any positive effects on mood or well-being or must come with such heavy side effects that no sane healthy person would willingly take them. For some reason, the medical profession considers the enhancement of one's quality of life beyond some arbitrarily chosen 'healthy' baseline to be forbidden, and is in cahoots with the executive branch to gatekeep it at all costs.
- hnlmorg 2y ago
  There are plenty of medical substances out there that are chemically similar to recreation drugs. Particularly in the fields of painkillers and anaesthesia.
- iancmceachern 2y ago
  Its not the medical professionals making these decisions. That's like soldiers choose what tanks they drive. They don't. These decisions are made by the hospital/insurance company "complex"
  - neilquinn 2y ago
    Nah that’s too recent This is all due to scientists having to obscure what they are doing to ameliorate the “don’t clone animals or build nuclear reactors” types. See the majority on the planet are intolerant religious groups. God has a natural plan types. We’re not to muck with it and to get jobs working for the rich God hand picked. So we had to invent jobs synthesizing drugs to get around stupid religion and the politics the religious controlled. And those innumerate politicians saw it as a way to make up a political agenda. There’s a whole lot going on in tech and science that’s just dumb jobs role play. Most of it just normalizing the math of relativity as physical science has bounded human story. Whole lot of people freaking out at that. System is falling apart with generational churn as experience is not evenly distributed; new people never experienced the past highs and feel the demands to not just use shrooms is corny af since no such ban really exists, it was just social paranoia of a prior generation.
mrangle 2y ago
Serenity Now, Insanity Later
more_corn 2y ago
One big problem with SSRIs is that they cause a massive down-swing when you’re coming off of them and they take two weeks to start working. I guess that’s two problems. If they were otherwise comparable and lacked those two negatives (which it seems they do) it’d be worth exploring them. They should certainly be reclassified away from schedule 1 since they clearly have a medical use. I think it’s also clear they’re not addictive.
homakov 2y ago
Every psychodelic experience is unique & random, even if the title was the opposite and in their study SSRI turned out to be better doesn't mean it will be better for you. From my personal experience, SSRI (zoloft) felt like a temporary coffee-like stimulant. Psilocybin (or easier to handle synthetic analog 4-aco-dmt) provided short-acting relief from depression and some new perspectives. But ketamine is truly a magic pill if done right. After glow is about a month, and the trip takes 2-3 hrs max. FDA-approved, see Spravato. I feel like at some point ketamine therapy at scale would make SSRIs obsolete, it's just better and faster.

582 points by Thomvis 2y ago

Didnt a lot of studies finally come out by 2022 showing that SSRIs are not actually effective for most people, no more than a placebo? And the whole link between serotonin and depression was spurious… 2021: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2776611 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/... 2022: https://www.jwatch.org/na55225/2022/08/16/antidepressants-work-only-small-subset-patients https://www.jwatch.org/na55225/2022/08/16/antidepressants-wo... 2023: https://www.nature.com/articles/s41380-022-01661-0 https://www.nature.com/articles/s41380-022-01661-0 In any case, I believe that ADHD, Depression and many other “umbrella” psychiatric diagnoses are being overdiagnosed, much like “hysteria” was for hundreds of years (eg 1 in 4 middle-aged women is on antidepressants now, and the opioid epidemic in men was largely exacerbated by the pharma industry, as has the overdiagnosis of ADHD prescribing amphetamines to kids). To be fair, the actual incidence of phychiatric conditions from ADHD to autism to depression has increased, as well as autoimmune disorders, diabetes etc. although not as much as the pharma industry wants us to believe. It could very well be the result of upstream changes in nutrition (eg wild increases in sugars like fructose across the board, antibiotic overuse on factory farms, buildup of microplastics everywhere etc.), and to a large degree society (including loneliness, dating, relationships, work, etc) and medicating them downstream (eg with amphetamines or opioids) is just a bandaid. Late stage capitalism has had a direct role in exacerbating this. For example, the tech industry (which many on HN are involved in) has redefined dating, relationships, job searches, political discourse, and much more. All of these affect how people interact. A seminal book even back in 2001 was “Bowling Alone” by Robert Putnam, who noticed Americans aren’t attending communal activities like they used to. Corporations have co-opted many movements (like women’s lib) to make people work harder, neglect their kids, eat unhealthy food, become obese, develop diabetes, lose sleep, and now be part of the gig economy etc. I like to show this Cadillac commercial from 2014 as a great example of the corporate brainwashing: https://www.youtube.com/watch?v=xNzXze5Yza8 https://www.youtube.com/watch?v=xNzXze5Yza8

seec 2y ago
Yeah that's just society absolutely wants to label/categorize behavior that appear to fall outside of the normal, most of the time failing to understand that those behavior have roots in the genetic makeup of the person as well as his personal experience. Most of the time there is nothing really wrong with the diagnosed perso but capitalist/productive society push for normalized behavior so that individuals have less difference and more exploitable/interchangeable. Funny thing is that you can make the arguments that many of those behaviors are actually adaptation to the environment and may sometimes be the future of humanity. That do not please the productivistes who want to extract as much value of every individual as possible, like we do with cattle. Now they are some very crazy people out there but it's a very small part of the population and you can often trace the problem back to genetics or physical impairement (environmental or else). Solving that sort of thing with drugs or therapy is basically wishful thinking, but it makes money so I guess that's ok... As far as I can tell the whole field of psychology/psychiatry is basically just one step removed from full on charlatanism. We can learn some stuff about people's behavior, take some moral judgment about what's good or not (changes with time as well as political viewpoint) but the drive to specifically categorize is a bit crazy in itself...
- neom 2y ago
  I read a bunch of your comments. For someone who has no idea what they're talking about you sure hold some dangerously belief. I'd strongly advise people to ignore folks who are clearly not experienced in something they profess to know about.
  - EGreg 2y ago
    What I said is factually-based The person who replied to me I think blew it out of proportion, and went beyond what is supported by facts While you may be right to caution people against the more reckless positions, I wish you’d also engage with what I actually said. Because the various industries thrive on exactly all of us policing each other and cautioning to not question all the convenient assumptions they are relying on us to perpetuate, to prop up the system.

jtrn 2y ago

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.

newsclues 2y ago

Taking LSD every few months was the best antidepressant I’ve ever tried and I’ve tried a bunch

drcongo 2y ago
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 2y ago
  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 2y ago

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 2y ago
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.
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- mtlmtlmtlmtl 2y ago
  Purely out of curiosity, which drug is this, if you don't mind me asking?
  - tootie 2y ago
    Sodium oxybate. Active ingredient is GHB. I was stunned to find out this was a therapeutic but apparently it was developed for potential therapies and was only coincidentally discovered to be intoxicating. I used to suffer debilitating cataplexy and sodium oxybate has nearly wiped it out.
    - mtlmtlmtlmtl 2y ago
      Right, GHB is an interesting one. It's always fascinated me how most recreational drugs are a wonderdrug for at least one medical condition. There are a couple of exceptions of course. Like synthetic cannabinoids. But even ethanol can be used as an antidote for methanol poisoning. For me it's amphetamine. I have severe dehabilitating ADHD-C and lisdexamphetamine has completely changed my life.
pier25 2y ago

ValentinA23 2y ago

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor#Sexual_dysfunction 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/ https://www.pssdnetwork.org/ At least, the mushroom didn't steal my mojo

cpucycling7 2y ago
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bitcurious 2y ago
Can psilocybin restore the mojo, or are you just commenting on the downside of SSRIs?
- erie 2y ago
  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 2y ago
    happy ending?

cpucycling7 2y ago

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 2y ago

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/ 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 2y ago
> 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 2y ago
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 2y ago
  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-ketamine-placebo https://www.astralcodexten.com/p/does-anaesthesia-prove-keta...
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BugsJustFindMe 2y ago
> 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.

stefantalpalaru 2y ago

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dillydogg 2y ago

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 2y ago
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 2y ago
  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 2y ago
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 2y ago
The doses of psilocybin being used were so low as to be barely perceptible.

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jdietrich 2y ago

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 2y ago

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.

rainclouds 2y ago
Psilocybin has always made me not want to drink for extended periods of time after use. Always saw that as a great benefit.
agumonkey 2y ago
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 2y ago
  Psilocybin tolerance starts building immediately. Even if you microdose (100 mg), it will stop being effective after 3-4 days.
  - vlabakje90 2y ago
    100mg psilocybin is several times a heroic dose, but 100ug is far below a microdose. Do you mean 100mg of dried mushrooms?
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    - dymk 2y ago
      I think he means 100mg of mushroom body, which might be 1-2mg of psilocybin.
  - dymk 2y ago
    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.

8b16380d 2y ago

Funny, psilocybin has been largely detrimental to the mental health of everyone I know.

api 2y ago
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_ 2y ago
my experience has been very different for everyone I know
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joemazerino 2y ago
Agreed with a caveat: SSRIs and other antidepressants are far worse.
giantg2 2y ago
"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 2y ago
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 2y ago
  Thoughts on Mescaline/Peyote?

state_less 2y ago

> "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 2y ago
> 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 2y ago
  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 2y ago
    The best thing to do is to consult with a physician on matters related to your health.
    - Wytwwww 2y ago
      Why? I mean it certainly depends but as far non severe mental health issues go physicians are just going to checklists since there is hardly anything else they can do (besides long-term therapy).

keepamovin 2y ago

But no patent, so this is "misinformation" haha

chiefalchemist 2y ago

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/ https://michaelpollan.com/books/how-to-change-your-mind/

sub7 2y ago

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 2y ago

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 2y ago
You could compare against other psychedelics. I’d be interested in that.
- zozbot234 2y ago
  You could also test it on severely sleep-deprived experimenters undergoing sensory isolation, but that would never get IRB approval.
  - roywiggins 2y ago
    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/september/sleep-deprivation-is-an-effective-antidepressant-for-nearly-half-of-depressed-patients https://www.pennmedicine.org/news/news-releases/2017/septemb...
- cubefox 2y ago
  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.

iluvcommunism 2y ago

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 2y ago
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 2y ago
  And it's mostly not legally acquired fentanyl that's killing people.
  - deleted 2y ago
    [deleted]

lumb63 2y ago

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 2y ago

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 2y ago
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 2y ago
  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 2y ago
    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.)

_iaoo 2y ago

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 2y ago
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?
- _iaoo 2y ago
  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.

modeless 2y ago

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 2y ago

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 fiancée 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 2y ago

No shit.

debacle 2y ago

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 2y ago
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 2y ago

Full research article: https://www.thelancet.com/action/showPdf?pii=S2589-5370%2824%2900378-X 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.

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thegrim33 2y ago

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 2y ago
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 2y ago
  Often you’re not allowed on your medication for any of your other health issues.
  - londons_explore 2y ago
    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.

shadowtree 2y ago

Ah, but does it beat exercise, fresh air and sunlight? https://www.mayoclinic.org/diseases-conditions/depression/in-depth/depression-and-exercise/art-20046495 https://www.mayoclinic.org/diseases-conditions/depression/in...

Molitor5901 2y ago

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 https://news.ycombinator.com/item?id=41283493

xterminator 2y ago

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 2y ago
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 2y ago
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 2y ago
  "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 2y ago
    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 2y ago

anonymouse3112 2y ago

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 2y ago
How do you even go about proper dosing and frequency of psilocybin use? Just random guess?
- snek_case 2y ago
  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 2y ago
  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 2y ago

pessimizer 2y ago

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 2y ago

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 2y ago

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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ein0p 2y ago

I’m pretty sure getting repeatedly punched in the head would “best SSRIs” in a long term comparison too. Hasn’t the entire body of research that gave us SSRIs been exposed as fraud a couple of years ago?

torginus 2y ago

I have a theory that the medical community has a somewhat antagonistic view on mind-affecting drugs that work and have genuine positive effects - it's that healthy and/or undiagnosed people will take said drugs willingly, as they provide their positive effects for healthy individuals, and they'll instantly get labeled as abusable drugs, whose consumption is tied to heavy criminal charges. This reputation and the accompanying legal red tape makes medical research into said compounds very difficult. An ironclad rule for medically approved drugs is that no fun is allowed - approved drugs must not have any positive effects on mood or well-being or must come with such heavy side effects that no sane healthy person would willingly take them. For some reason, the medical profession considers the enhancement of one's quality of life beyond some arbitrarily chosen 'healthy' baseline to be forbidden, and is in cahoots with the executive branch to gatekeep it at all costs.

hnlmorg 2y ago
There are plenty of medical substances out there that are chemically similar to recreation drugs. Particularly in the fields of painkillers and anaesthesia.
iancmceachern 2y ago
Its not the medical professionals making these decisions. That's like soldiers choose what tanks they drive. They don't. These decisions are made by the hospital/insurance company "complex"
- neilquinn 2y ago
  Nah that’s too recent This is all due to scientists having to obscure what they are doing to ameliorate the “don’t clone animals or build nuclear reactors” types. See the majority on the planet are intolerant religious groups. God has a natural plan types. We’re not to muck with it and to get jobs working for the rich God hand picked. So we had to invent jobs synthesizing drugs to get around stupid religion and the politics the religious controlled. And those innumerate politicians saw it as a way to make up a political agenda. There’s a whole lot going on in tech and science that’s just dumb jobs role play. Most of it just normalizing the math of relativity as physical science has bounded human story. Whole lot of people freaking out at that. System is falling apart with generational churn as experience is not evenly distributed; new people never experienced the past highs and feel the demands to not just use shrooms is corny af since no such ban really exists, it was just social paranoia of a prior generation.

mrangle 2y ago

Serenity Now, Insanity Later

more_corn 2y ago

One big problem with SSRIs is that they cause a massive down-swing when you’re coming off of them and they take two weeks to start working. I guess that’s two problems. If they were otherwise comparable and lacked those two negatives (which it seems they do) it’d be worth exploring them. They should certainly be reclassified away from schedule 1 since they clearly have a medical use. I think it’s also clear they’re not addictive.

homakov 2y ago

Every psychodelic experience is unique & random, even if the title was the opposite and in their study SSRI turned out to be better doesn't mean it will be better for you. From my personal experience, SSRI (zoloft) felt like a temporary coffee-like stimulant. Psilocybin (or easier to handle synthetic analog 4-aco-dmt) provided short-acting relief from depression and some new perspectives. But ketamine is truly a magic pill if done right. After glow is about a month, and the trip takes 2-3 hrs max. FDA-approved, see Spravato. I feel like at some point ketamine therapy at scale would make SSRIs obsolete, it's just better and faster.