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?
>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.
They got 'matched' support, which reads to me as 'equivelent':
"Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET)."
>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?
This is only the follow up portion, and as secondary measure at 6 weeks. The original study (https://clinicaltrials.gov/study/NCT03429075) says the primary measure was; "Change in blood oxygen level dependent (BOLD) signal during fMRI in response to emotional faces during an emotional faces paradigm done inside the fMRI scanner." at 6 weeks vs baseline.
>The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group.
Statistical significance is based on sample size, and is independent of population size. Let that sink in, doesn't matter if your population is 100K or 8 billion, when you sample you are trying to understand the probabilities in your sample, not in the population.
Therefore, (think about the birthday paradox, doesn't matter how many people in the world, a few dozen in the room with you is an adequate sample), it should not surprise you that statistical significance is achieved through a much smaller sample size than most non-statisticians have intuition for.
> few dozen in the room with you is an adequate sample
It's not, though? Unless you're fine with a very high margin of error... Also the sample in studies like this is hardly ever close to being random anyway.
> it should not surprise you that statistical significance is achieved through a much smaller sample size
Margin of error only occurs when you expect high variability and a very large population of measurements. When the set of potential measurements is of size 2, having enough statistical power can be achieved with very low sample size. Anyways, many results have survived stage 4 analysis (real world, observational, administrative documents sourced), even when their OG sample size is relatively small.
No, psychology studies have been traditionally very poor because most of the theory was literally out of someone ass, without proper design. Newer studies have been shown to be very robust, public freakout notwithstanding.
>Therefore, (think about the birthday paradox, doesn't matter how many people in the world, a few dozen in the room with you is an adequate sample), it should not surprise you that statistical significance is achieved through a much smaller sample size than most non-statisticians have intuition for.
This response on the supposed the lack of importance of a sample size is completely wrong on just about every claim. The parent comment had a valid point. Just because a population may fit a certain distribution, does not mean that any given sample size will also fit that distribution. Samples are used to ideally create a representative group of a population, that is smaller than the population. However, the sample size required to come close to a representative distribution can vary between populations and variables being examined. Also, using the birthday paradox is a terrible example and has nothing to do with statistical significance, as the so-called birthday paradox is just a simple function.
Except that sample size doesn't matter if the set of potential results/measurements of the dependent variable are very large. Someone pointed out that you can demonstrate that alcohol impairs executive functions, balance, etc. with a very small sample size, because the effects would be so large and evident that your statistical power would be. On very large variance, where the results are dichotomous in nature (can a subject walk straight in a 10 meters line, without walking outside: yes/no) can have a very small sample size.
Use this calculator, set options to: two independent groups, dichotomous, group 1 = 90%, group 2 = 10%, incidence, enrollment ratio = 1, alpha = 0.05 and power = 80%. The sample size is 10, 5 for each group. https://clincalc.com/stats/samplesize.aspx
That other comment on alcohol is by the same guy that made the comment that I responded to here. The same issue there is that result reliability can be influenced by the effect size of the variables being tested, but this still is far from a guarantee that the results will generalize, which is more likely to be an issue with a smaller sample.
An issue with the comment I previously responded to, as I mentioned above, is that they made it out as if a small sample size could be reliable to determine a reliable statistical significance irrespective of the variables under study and tried to prove this by using an absurd analogy between statistical significance and the birthday paradox. The problem with their attempted point was that it didn't even respond to the comment above it, which pointed out that a high statistical significance is not a guarantee of reproducibility, especially with a low sample size.
Sample size only matters for statistical power. After certain point, the diminishing returns will fall of a cliff. Lay persons seems to have mistrust of seemly small sample sizes, but they need to understand that doubling the size of the study only improves statistical in 5-10% for dichotomous studies. If we mandated a bigger sample size without taking into account why it's relevant and how it's calculated, it will make every study cost prohibited.
The issue your parent comment raises is that this random group may not represent someone that's trying to evaluate what techniques can help them, regardless of the statistical significance within that group. It makes me sad that they introduce other random variables, as incontrovertible evidence of efficacy could help a lot of people!
except it was completely non-specific about what those flaws might be, simply saying "sample is too small" when the sample is not a priori too small for a properly designed study of something that has "noticeable" effect. For example, "does alcohol get people drunk" is not hard to show on a sample of 10 people.
A larger sample size isn't inherently better, but if a large sample size from a diverse enough pool of people can be used to eliminate and/or identify confounding variable and distortions.
Just the first line alone "Statistical significance is based on sample size, and is independent of population size", was bizarrely silly in its description of the use of sample sizes, before they even got to their nonsensical analogy to the birthday paradox.
> 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?
They try to make for no comorbidities and and for MDD that is pretty rare. It also means that we’re often studying rare configurations compared to those commonly seen in actual practice. Statistics doesn’t like confounding elements and humans are very confounding. So either you get “bad” statistics, or you get “bad” data. And why you have front line drugs that only have a helpful effect for 33% of people.
Just to add one minor detail to this very good explanation: even if you could find 500 participants matching the criteria instead of 50, you wouldn’t want to “waste” all of them on your first study design.
Its expensive. Statistically speaking its really not that small. You can always argue p hacking but these are always useful as a means to do further research
> If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"?
Those are design descriptions.
Double blind means that neither patient nor the one administering the treatment knows which is which. Randomized only means that each subject is assigned randomly a treatment group. Controlled trial just means that the study design made sure that other variables that are not under experiment are also under control. Nothing about this preclude actions done to the subjects nor sample sizes.
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.
That's not generally how drugs work. There's wide margins on how much dose is required for clinically significant results. Not only is the 110 pouns petite woman taking the same dose of aspirin as a 400lb elite powerlifter, but the effects can't be quantified in high resolution. The woman can't say her pain was 5% less than the powerlifter, and they can't say their pain was 5% more.
I mean it sounds like a way to trick people into letting a giant company build a surveillance system, and I imagine aliens observing humans in this moment in history might conclude that's what we want, but for science or the benefit of the people "surveyed" it's mostly downsides
TBH there's no way to have a double blind trial of drugs like psilocybin (Scott Alexander has written a little bit about this [1] with respect to controlled trials for MDMA), for any reasonable dose size of psilocybin. Both the patient and the person administering the drug will become very aware, very quickly, if they're in the psilocybin group.
Unsurprisingly, the way around it is to introduce a third treatment or fourth, with classical psychedelic 5-HT2 action. There are a few such choices and some are also registered antidepressants, one being DXM/bupropion, another being an ergoloid derivative or a psychedelic amphetamine like DOM.
But then you need to run a trial in a hundred or two hundred N.
This is wrong. You can absolutely dose psylocybin at levels that make a meaningful difference in experience (certainly enough to have an anti-depressant effect) without “tripping” or being in any way impaired. For many adults, this will be around 100-200mg of psilocybin.
Microgram, not milligram, of psilocybin. 100mg of psilocybin would be about 50-200 grams of dried cubensis mushroom.
There have been studies on microdosing, but it’s also valuable to know what happens at perceptible doses as well. It’s certainly a different experience.
Therapy is such a wash statistically that I'm not particularly confused or concerned by that, and everyone that has ever taken psylocibin knows the results are typical.
It’s kinda interesting you say that because studies show that SSRIs are not much better than placebo for treating depression, and that therapy plus SSRIs is the best treatment available right now.
The article states that both groups received psychological support though. The only mention of 20 hours I find in the article is as an option to psilocybin. Does the original research article say something else?
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.
Thanks for sharing this, you’re not the only one. I have a close friend who tried LSD as a last resort to get the best of his severe depression and suicidal thoughts (after being on SSRIs for his entire life) and just one session completely removed his suicidal thoughts for months. After this experience he repeats this whenever he feels the dark thoughts are coming back and it always curbs them down almost completely. It’s mind-blowing how well it worked for him.
just consider, if it's so powerful in adjusting his brain, it's probably equally powerful in adjusting anybody's brain, and what if your brain doesn't need adjustment? there's no reason to think it's "idempotent" so to speak.
https://en.wikipedia.org/wiki/Idempotence is the property of certain operations in mathematics and computer science whereby they can be applied multiple times without changing the result beyond the initial application
My experience with psychedelics is the following: they shift your perception of things temporarily. The way the "adjustment" works is that you are able to "see" and "touch" experiences you could not before, because they would have annihilated you. They open a door to re-living things and re-processing. Hard for me to see that you would come out of that "broken", if there's nothing to process your trip will be a pleasant high.
Which is not to say that psychedelics (LSD, 2C-B, Mescaline, Psilocybin) are not powerful stuff and that they allow for mental states that would be unlivable otherwise (clinically that would be schizophrenia or something like it). I do believe that their therapeutical and recreational benefits do outweigh the drawbacks though. There must be a better way to handle this than Schedule-1'ing the whole bunch.
Powerful they are indeed. Depends on general personality, current mental situation, dosage taken, environment and/or people setting up the vibe. That's why I think they should be 100% available but 100% only under professional supervision, who has chemistry and skills to stop the trip gracefully if needed.
I've only ever done them (mushrooms) alone, mixed with fresh lemon juice that somehow makes them more intense and shorter-acting (say 2.5h very intense trip I prefer much more than 6h of less intensity). A profound, maybe a bit life-changing experience. Laying down, eyes closed, listening to some mellow shamanic music, I went far and beyond anything I can explain with my words, dissolving senses, myself, and putting it back again afterwards piece by piece.
It was pure goodness and positivity, but I can imagine if it was so strong but negative it could have been soul-crushing. Pair it with already fragile personality and the need for professional oversight is always a good idea IMHO. Educate on top. Ignore on your own risk.
I suspect there’s a lot of self selection at work already. The vast majority of people don’t jump straight into psilocybin and LSD, they progress to them by taking softer drugs like alcohol and cannabis. I think a lot of people who don’t need “adjustment” figure out drugs don’t do much for them and stop before they take the intense psychedelics, or they figure it out at lower doses and stop before they take the intense dose.
Are you saying the claim that psychedelics are effective treatment for depression, PTSD, addiction etc. are simply because those who try it suffer those conditions? What about the part where they say it works effectively? Because I don't think alcohol or cannabis are claimed to be an effective treatment for these conditions in the same way that psychedelics are. The idea that it works seems irrelevant to your conclusion.
sounds like a reasonable hypothesis, that people who are unhappy with their emotional/mental state might be more attracted to altering it, or might experience results they consider more positive.
how do our brains decide to do anything, like eat ice cream? "hey, I loved that last time". We know that drugs are not experienced as universally positive because many people who try them in college do not go on use them throughout their adult lives.
But the part you miss is that it works. This is anecdotal for now but people are looking at evaluating that more objectively.
It's not even a stretch if you squint at this. The currently accepted treatment is SSRIs, the second S standing for serotonin. Psychedelics work on serotonin receptors. Why would it be surprising that if you tweak your serotonin receptors, you get treatment for depression? Again, this is not true of alcohol or cannabis.
everyone considers that, but because they’ll be dead by the time the studies narrow down anything they chose the substance that moves them towards results - or doesn’t
everyone can perceive that psychedelic is doing many highly variable things at once and probably shouldn't be recommended, so they just say their experience
the vast majority of people who try psychedelics are not trying to escape untreatable clinical depression, they are doing it recreationally, for a roller coaster ride which they believe connects them with the Almighty or the Unknowable or the Dao or the All-loving Everpresent or the "insert word that sounds profound" <-- oh, the Profundity!
These people are inspired—perhaps by the Almighty, i'm not judging—to preach The Gospel of psychedelics and praise any confirmation of these miracles. I'm simply pointing out that what appears to be the Omnipotence of the Almighty might very well be Selling Your Soul to the Devil for all you know. I'm an atheist, simply using metaphor to get the point across to you.
When you talk about how powerful medication is in warping the brain to cure intractable mental problems, that is not at all an endorsement of recreational use. Heroin makes you feel like your mother not only loves you, but makes up for her not loving when she abandoned you as a baby. Is heroin therefore a good idea? (and if you say "that's chemical dependency", you completely miss the point)
Idk how many people trying psychedelics for the first time are that interested in the shamanic gods or whatever as much as they want life altered in a fun weird way. In college when people did LSD or mushrooms, they were usually most interested in the visuals.
what point do you think needed to get across to me? did you think you were replying to someone else? my response was sufficiently broad to factor in non-positive and negative experiences and had nothing to do with the hyperbolic praise of some psychedelic users and that community
turns out I don't write my comments just for you. what did you write that you think so clearly showed you understood what I originally said that I wouldn't think other people suffered the same misapprehensions?
I have tried and use those things (mushrooms, LSD, MDMA) just for fun and I think they are alright if you understand that it is just that: a fun experience, like alcohol or cannabis can be.
But I agree that there is a large amount of people taking those things and coming up with large amount of bullshit to justify taking it, in an attempt at pretending that they are more than just fun. It's always people who are very status conscious, hipster like, with narcissistic tendencies who want to impose their viewpoint in a way that makes them feel superior.
As far as I'm concerned, I think those things should be legal because not only sourcing them is easy anyway but it also escapes all quality control and regulation even though we still agree to sell much worse things as a society (like tobacco) and that's very incoherent.
I don't think any of the new age bullshit theory about healing mental illness (an already loosely defined thing) or whatever else is correct, but what is probably true, is that most of the stuff sold by the pharmaceutical companies is not any better (when it's not much worse) yet it is legal.
This is a classic case of capitalism bullshit: if you are having fun, you can't be a productive individual so that's not right, but in the meantime please buy our very similar drugs that's supposedly have the same results, without the fun.
One reason the advocates are going overboard with all the claims is probably because the industry is allowed to do the same with much less scrutiny, so it is an attempt at equilibrium, I guess.
I doubt they will be successful at fighting fire with fire but it is annoying that it is such a political issue, people should be allowed to take those things if they want to...
although I criticize the same people, I think your viewpoint is too dismissive
without prior knowledge of what psychonauts say, I also experienced increased empathy or ability to relate to more people and animals. body language, cues, things that maybe come with mental development or maturity but seemed more refined and accelerated. on the empathy and EQ, it seems to wear off. so noticing that is a shared experience is fascinating to me, I wish it could be controlled for specifically to refine that aspect of the substance or trigger in our minds instead of jumping into the debate about legalizing that specific substance, and I understand the limitations in testing it, both from a legal and regulatory standpoint and from a control group and study standpoint
this leaves us at square one, where I can appreciate others experiencing it but I cant quite recommend either due to how varied the experience is
Same. I came to them as an older person (late 40s) who basically had only tried pot a few times prior, and nothing at all before late thirties. I don't drink.
My few experiences, the first few times, over the course of a year, spread apart by 3-4 months, went from extremely dark to .. just positive, except the last one, where I had no visuals, no bliss at all, and just came to terms with something else in our lives that was going wrong.
The dark ones were rage and anger, and now it seems just gone, like there's nothing there. Like a weight lifted, and seemingly long term.
If you are in the sf bay area, you can just go get what seems to be a variety of high quality, and some tested and stamped (Netherlands) mushroom products at Church of the Zide Door
Can you share some info on how much you took, and in what setting you took them, what you did on the trip, etc? I have a bunch of shrooms sitting in my cabinet but I havent had got any life altering effect out of them.
Yes, that's pretty normal, that's actually expected behavior. I think people saying it changed stuff are the ones having a problem in the first place (reality perception, lack of sensitivity or whatever).
Just like alcohol, those things are basically a poison, that you do not die from, provided you don't overdose (you probably have more chance dying of alcohol than mushrooms but still...).
People should take them to have a bit of fun, just like getting inebriated with alcohol and moving on with their life.
Beware of people who tries to pretend more, that are most likely full of shit and you can probably ignore most things they say if they lie about that...
This would actually be my preferred trip. I just want to have fun, its been so long since I had genuine good fun. Im tired of all the mental reflection.
I did 3 sessions of 8 grams in silent darkness for 3 weekends in a row and that basically "beat the devil out of me" as they say - it was very very difficult, and a lot of work, but well worth it.I've only felt the "brain haze" (I call it) once since then, I took a gram and went for a long walk in the forest, back to no haze. It's been about 7/8 months and I can feel the "haze" building in my mind again, so I plan to do another 1g in the forest sometime in the coming weeks.
However, my personal experience has been that Psilocybin != Psilocybin - the mushroom itself is super important to the process, much like Indica and Sativa have different ways of connecting you to the mind and the aether, Psilocybin (at least for me) VERY much is the same thing, and it's much starker than cannabis is. Getting into woo-woo land here so apologize: I have some concern that just "Psilocybin" isn't a good prescription, that the "spirit" that works on you is unique to the mushroom family, and that both not knowing the mushroom to prescribe and also being clinical about it (Psilocybin vs Mushroom) may not be a good direction to go in to help people with their issues. I also think that about LSD, it might work a bit for a while, but imo it's not the best tool.
Totally agree. The variance between species can be dramatic! 2.5 grams of Golden teacher was a standard trip, vs 0.5 grams of PES Amazonian was enough to send my friend into a full blown “awakening” (physical responses and everything).
It’s fascinating how they can hit different.
Also important to keep in mind the same dose can hit someone different each time depending on surrounding life conditions. I’m a big believer that the mushrooms “show you what you need to see” at any given moment, and that can sometimes range considerably.
> The variance between species can be dramatic! 2.5 grams of Golden teacher was a standard trip, vs 0.5 grams of PES Amazonian was enough to send my friend into a full blown “awakening” (physical responses and everything).
Hallucinogenic experiences are rarely the same. So you can use the same amount of the same batch 3 different times and have 3 totally different experiences.
Some people claim that you can control experiences by contolling "set and setting." I don't buy even that; all we can really say is that the experiences are not consistent between trips and we don't know why.
Anecdotal case study involving a community of about a hundred enthusiasts: many in this community held the opinion you do, which is that something about the mushrooms themselves is unique to the psilocin experience (psilocybin is not always present, and in any case, metabolizes to psilocin).
Then 4-actyl DMT, sometimes call psilacetin, became broadly available. This is a synthetic pro-drug for psilocin, just as psilocybin is a naturally-occurring pro-drug for psilocin.
After that, the opinion that the mushroom per se had anything to do with the experience became very rare. It turns out that psilocin is meaningfully different from, in particular, LSD, 2C-B, and MD(M)A.
There's definitely something special about it. But that something is also present when it comes in vitro, not just in vivo.
8 grams in one sitting? Im not even so worried about the psychological response but even a gram can give me extreme stomach pain and nausea that ruins the whole thing.
LSD has somewhat the same effect but in a cleaner way. It's not really about the mushroom itself or the way you ingest it.
That being said, mushrooms are not very good regardless so you can process them in a way that makes it palatable (teas, blended smoothies, etc).
But that won't make that weird nausea feeling disappear, you just get used to it and it slowly becomes unnoticeable as you progress on the "experiment".
The nausea is a response of your body, telling you that you ingested something bad, because that basically what those things are: a poison, just a non-lethal one, and we know the positive fun effects so it makes it worth it, otherwise you would just want to throw up !
I havent had the same effect from LSD, I also didnt have it the first few times I took it weirdly enough. I think how anxious you are seems to determine how much attention you give to the stomach pain.
Last time I was sitting there miserable for an hour and I started thinking this is life in general. I can either continue to cry about the bad or try and fill my time with something positive. I started to take a walk and think more positively and it seemed to do the trick, for a bit anyway
8g dried, overnight in lemon juice in the fridge then in the blender, chug a small glass of some type of smoothie from the store, chug the mix, chug a bit more smoothie, get into bed totally naked, wait. I did a looot of research and talked to a lot of people who have been down this trip and decided just to remove the variance of middle dose land and just put myself in "not aware" set. It worked well for me, ymmv.
My friend once described to me how mushrooms differ from alcolhol: With mushroom you get the hangover first and then the high. With alcohol it is the opposite.
^^^ much like the terpenes in weed different mushrooms have different chemical compositions that alter the way your body interprets the psilocybin. Cubensis make me laugh/most folks I know get the giggles on them. Blue meanies make you see things (super visual). Or atleast this has been mine and others experience over eh, probably around 20 to 30 trips over the years.
Lsd is good but definitely not as good or as easy on the brain as mushrooms. Dmt is wild, dmt with a maoi I'm too scared to try.
I've tripped a lot. It's my preferred way to party, but these days I party rarely. Mdma,ket,coke,heroin,speed all leave me feeling gross and the risk factors for addiction are far too high for my liking.
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.
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"
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.
There are plenty of medical substances out there that are chemically similar to recreation drugs. Particularly in the fields of painkillers and anaesthesia.
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
Unfortunately it's hardly possible to do proper case control studies with psilocybin, since the psychedelic effects cause unblinding.
This is a problem with SSRIs as well; studies have found most people can correctly guess if they’re in the study group or control group.
A true double blind study would require a drug that has similar side effects via an unrelated mechanism, but nobody has attempted that as far as I’m aware.
There was this interesting one though where they deceived patients into believing they were taking an “active placebo” instead of an SSRI, and found that the benefits went away, which is very interesting and raises a lot of questions about the true efficacy of these medications: https://www.nature.com/articles/s41398-021-01682-3.pdf
If there is a medical question that double-blind studies cannot answer, that doesn't mean the question is unanswerable. It means we should be more skeptical of non-blinded studies (or worse studies that pretend to be blind), and we should look for alternative ways to address biases.
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.
There are many hints at psilocybin not being different to LSD, some researchers opted for psilocybin for trials just because it was less known to the wide audience and had less cultural baggage than LSD. There are some comparisons, e.g. https://www.nature.com/articles/s41386-023-01607-2
Hardly an issue. When people do similar studies measuring say the effects of prescribed exercise vs not they are also unblinded but we still get good data.
I've never found it compelling that blinding isn't possible for drug-naive patients. There are other drugs that could induce a "trip" and an unfamiliar individual could mistake for a minor psychedelic experience.
When you don't know what a psychedelic experience is, any mind altering substance could do. For someone who never got drunk, it could even include alcohol.
It is very hard to describe in words what a psychedelic experience is, so without a reference point, it is hard to tell if what you experienced is one or not.
Is alcohol the best you could do? I have a feeling that alcohol can definitely help with depression Probably one of the oldest drugs used in that regard
of course there aren’t actually that many drugs.. you clearly couldn’t give another tryptamine they are kindof all the same. I guess you could give a phenethylamine but obviously those are probably good at treating depression too so your studies gone to shit I suppose you could give a deliriant but that just sounds mean.
Suggestion alone can make you feel high. I remember someone telling me that he got high just by touching sweaty people in a music festival where most people were high, clearly, that's placebo. And that guy was far from drug-naive.
And they sometimes give active substances to the control arm to have an effect. I remember in a covid vaccine trial, they gave the meningitis vaccine to the control group to mimic the side effects of the covid vaccine they tried. Here, they actually gave a microdose of psilocybin (1mg) to the SSRI arm. I don't know why, but maybe it was enough for them to feel something without having the full effect.
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.
> we do not know, really, what goes on in there when you take a drug like Psilocybin
FYI, same goes for SSRIs. The scientific consensus is that the serotonin deficiency theory of depression was wrong. When SSRIs actually work, we still don’t know why.
I’ve had bad trips, too. Very bad, but I still think that psilocybin (in a controlled, supportive setting) is a better bet. My bad trips were all due to being in bad settings and being completely unprepared for what could go wrong. I was young and dumb and just fucking around. But tripping in positive supportive settings was incredibly helpful. And if we do find a way to do this right, then people don’t have to take drugs for the rest of their lives. Psychiatric drugs are generally lifelong sentences, and negative side effects tend to compound over time, which often leads to polypharmacy, and more side effects.
SSRIs barely work. For mild to moderate depression a placebo works similarly or better. Only for severe cases of depression are SSRIs found to be helpful because they surpress all emotion.
~50% response rate for people with major depressive disorder isn't "barely working" -- for millions of people, SSRIs significantly improve their quality of life. Unfortunately, there is no "one size fits all" solution and often those of us with MDD have to try different medications, in conjunction with a (good) therapist before we find what works best.
Personally, I've run the gamut on SSRIs and they never suppressed all emotion.
Maybe the effect is different when prescribed for something other than depression, but I did not find my SSRI to suppress my emotions. It simply helps me curb rumination and negative thought spirals. Helps to feel "lighter" and simultaneously more grounded. If anything, that allows me to feel _more_ positive emotion rather than suppressing it.
Cool, glad you had a positive experience. My experience was the opposite: emotionally numb to the point where awfully bad things happened in my presence and I barely shrugged.
Being unable to feel joy or pain, being unable to cry when a loved on passed on; these were the hallmarks of my time on SSRIs. Never again will I subject myself to these drugs.
It took me twice as long to get off them as I was on them. Two years of prescribed meds, 4 years to get off them. Six years of my life spent as a literal zombie person.
We don’t know why they work or don’t. Our experiences are just anecdata.
For folks that are interested in anecdotes about psychedelics, I recommend reading Erowid expertise vaults as what gets volunteered here is very narrow and not representative of the population as a whole.
I would know, as my psychedelic mega dose stories are very different from this and also completely unique to me.
I’ve done 500ug of LSD and it was great fun. I scheduled a day off to rest ahead of time and was back to normal after that.
250ug of LSD + 1 full ounce of golden teacher psilocybe cubensis and had a somewhat spiritual experience, took a couple days before I wanted to resume normal life.
+ a dozen or more similar stories
There is a reason why “set and setting” is repeated so heavily when instructing people on how to use these substances. Any discussion of potential subjective benefits or harms of a psychedelic in the context of an experience without specific accounting for that is fundamentally incomplete.
That being said, if my experience sounds ridiculous to you, that’s because it’s unique to me, just as others’ are unique to them. There isn’t really much to be gained by talking about individual experiences other than it’s an entertaining topic of discussion. It gets everybody exactly nowhere closer to establishing the objective clinical value of these things, though.
I very much disagree, the effects are extremely similar, to the point where if one could match the active substance dosage as well as absorption rate, you would be very hard pressed to tell the difference.
The relative difference is because people generally don't process their shrooms very well and they take much longer to digest (slower release over time) and also its very impossible to judge the potency of the shrooms beforehand (so most go on the safe side dosage); as a starter shrooms are more unpredictable than truffles.
I had the same argument with a friend who gave me a bit of LSD (total dosage unknown, it was edible) and I tried a few days ago, it was basically the same as good shrooms. In fact, I believe the dose was on the low side, it was faster to take action but the "core" experience was shorter and "lower" than just 15 grams of good truffles.
The only thing with LSD is that it takes longer to completely clear out of your system (because it is already extracted in pure form, while shrooms have to be digested/processed by your system in a less efficient/effective way) but I don't like that very much because you end up in this in-between state where you are clearly not high anymore but also restless with secondary effects that are not really cool/interesting.
In any case it would be rather surprising if it was different, because molecularly they are extremely close.
None of this is true, for various reasons. Psilocybin and LSD are qualitatively different above very low doses. They have a lot in common, but only a person that is basically unfamiliar with one or both would call them identical. The experiences become more distinct the higher the dose.
Psilocybin/psilocin has different binding affinities than LSD, is metabolized differently etc. They are, quite simply, different drugs.
>The only thing with LSD is that it takes longer to completely clear out of your system (because it is already extracted in pure form, while shrooms have to be digested/processed by your system in a less efficient/effective way
This is borderline gibberish. The “purity” of the “extraction” (???) has nothing to do with metabolism, protein binding or excretion. The LSD expense typically lasts longer because… it is a different drug. Your body treats it differently than psilocybin because it is different from psilocybin.
And the molecules do not look that much alike, unless you think that all indoles look alike. Even if they did, molecules that look alike do not necessarily act alike (eg H2O and H2O2)
'great fun' seems like a weird way to describe a 500ug trip. Did you have some tolerance before this, and do you have very high confidence that the dosage is accurate?
I picked “great fun” as a description as a shorthand because, while I could write more about it, it had little to no net positive or negative impacts on my mental health. For the purposes of this discussion, “Great fun” is kind of meant to communicate that the story is neither a warning or a recommendation regarding depression or any other mental health condition.
500µg is an immense dose, unless you have tolerance. Tabs usually have much less than the claimed amount. What was the source and form that makes you think 500µg is accurate? When it's 250µg or more, it's so overwhelming that many people don't have recollections from the trip after some point.
I didn’t write an extended trip report of a massive dose of LSD because this isn’t erowid and the details of the trip itself aren’t relevant. I brought it up as an example to contrast the post I responded to, as my experience was different regarding long-term effects
I was very aware of and confident about the dosage and I had not had any psychedelics for months previous, so tolerance was impossible (also no medication or other drugs etc)
I believe there is a point after which the higher dosage doesn't change much, but the duration of the trip.
I have noticed the same effect with mushrooms (truffles) where basically doubling the dose didn't do much.
I'm not even sure it lasted that much longer, because of course you don't take them in a fixed reproducible setting where you could correctly compare stuff.
I think there is a lot of bullshit around those substances, pushed by shamanic type of people who just invent and repeat nonsense to appear unique/interesting.
The "reports" on Erowid, while interesting in a way, are also so full of nonsense that it's largely irrelevant as a source...
I was just pointing out (mostly to other users who read this) that the alleged dose is immense and would be overwhelming for most people. Wasn't questioning your experience, only asking out of curiosity about the kind of source and form that makes you confident about the dose.
I did various journeys - initially alone, then with an experience guide.
Mostly to explore a childhood trauma - mild, but traumatic enough to leave me with a stutter.
There were indeed some "bad" trips, although I really do not like the term "bad". IMHO there is no bad journey, it is stuff that needs that wants to be seen.
Nor is the journey itself what counts, one cannot expect a quick fix from a 4 or 5 hour journey. What really counts is the preparation (4 to 8 weeks) before, and integration afterwards (again 4 to 8 weeks). In my case I also paired it with years of therapy and meditation.
It takes a lot of courage, especially to continue after an unpleasant experience (fear, grief and loneliness in my case). In my case I kept coming back and allowed myself more and more to let the bad experiences happen. Finally I just learned to be with what is, and accept things and myself the way it all is. With that came a measure of peace and insights I had not experienced before. Along with visions about the structure of existence.
But I'll stress again, just popping a mushroom won't get you there :)
Did you take it in a controlled environment like the study suggests? Every time serious conversation of medical progress comes up, it's polluted by naysayers with anecdata about how they took it while raving beside a live volcano.
We need to give psychedelics a fair chance, and sure after we can discount them. The article suggests at scale there is potential
In my experience (this thread, too), the conversation gets polluted by people that swear by their self-medication and call more cautious people naysayers.
How come every time we try to have a conversion, it always ends up all "point counterpoint" and "personal experience with the topic" and "differing personal experience" and "discussion of how those experiences relate to the topic"!? EVERY TIME!
Empirically, they're usually not nearly as useful as people think. People are on average unreliable observers of their own experiences.
Much better than individual anecdotes are collections of anecdotes that are searchable and somewhat categorized. A lot of old school drug forums provide this.
Much better still is systematically varying data and taking statistics to separate signal from noise.
In the pre-modern world people had a very different relationship to death and there wasn’t anything like anxiety as its experienced today. Psychedelics are essentially an attempt to bring someone back to a more “authentic” experience of life before technological controls settled in. Perhaps its better to take the chance? I think so, but I want others to recognize it as a genuine risk that is truly unpredictable and not a personal failing on the part of the user.
I wonder what you mean by saying there wasn't anything like anxiety as it's experienced today in the premodern world. The term "anxiety" comes from Latin "anxietas", and Old English had "angsumnes", both with apparently similar meanings, so it seems the idea has been around for a while, and most likely because it's a basic human emotional condition that could occur in various circumstances throughout history and prehistory.
As for a relationship to death, it's difficult to generalise over all people throughout history, but for example in medieval Europe where you had a seemingly quite vivid belief in the possibility of hell after life, that could result in some extreme anxiety of the most inescapable kind. Maybe that accounts for some of the more extreme behaviours of those times, who knows.
As someone who was experienced with psilocybin some 20+ years ago, I always took fairly consistent doses (roughly 3 grams), as I could sense taking much more would be playing with fire. This was pretty much a given amongst my circle of a dozen friends who experienced these trips with me… hero doses were almost never a good or healthy idea. Fun to read about on Erowid though, mostly as cautionary tales.
My time with the substance ended after two bad trips (after a few dozen great ones over a period of 5 years), but neither produced any sort of even minor lasting effect.
Hindsight is 20/20 but often it’s not clear at the time if it’s a bad idea or how bad it can be. I think it’s not such a fair question to someone struggling to find effective treatment for mental health issues to make a mistake on dosing. Especially given both government and medical field have historically not amenable to openly communicating harm reduction or safe guidelines for experimentation with this particular medicine.
Anyone who has ever tried to fine-tune medication for psychological issues knows how challenging it can be to get the dosages and combinations just right. In my experience, even medications within the same class can have different effects on different people, especially when combined with drugs from other classes.
The interactions between medications, as well as the patient’s individual response, are hard to predict. These reactions can change over time, too, as bodies and brains adapt, and lifestyles shift.
Yet, you often hear oversimplified statements like "depression means you have too little serotonin," "feeling sluggish means you lack noradrenaline," or "difficulty focusing means you have too little dopamine." These explanations are so reductive that they barely make sense.
The more I read about drug trials, the more I realize how little I — and even many professionals — truly understand about how these medications work and the best way to make informed treatment decisions.
> Ok like most of you I’ve taken psychedelic drugs.
I would like to see some actual data because my assumption has always been that most people have never tried any. I personally have not had any. I have always subscribed to the slippery slope theory of vice.
I literally take psychedelics once every few months to keep myself healthy and avoiding the dopamine chasing that I otherwise slip into over time. Shockingly not all drugs are the same, or even that similar and the propaganda about drug use escalation is, I'm sorry, silly.
>Thoughts came out of nowhere, I had no control over them; often the constant, unceasing flow of thought was distressing and uncomfortable.
I want to touch on this. "You" never have any control of your thoughts, because "you" isn't really a thing. Psychedelics and meditation teach us this if you pay close attention. The thoughts arise from nowhere and we - the imagined, but illusory - self are mere observers along for the ride that is consciousness.
I can imagine that using a substance such a psilocybin could cause your thought patterns to have both short and long term changes in quality (in terms of substance, not of superior gradation), however. It's also possible that your experience led to your paying greater attention to the thoughts that did arise, and over time the feedback loop of consciousness along with taking better care of yourself led to greater moderation of their genesis.
"You" can learn to steer your mind by choosing which of these thoughts to capture and dwell on, by monitoring them.
There is voluminous writing in the area of monastic spiritually about this. On the one hand, they affirm that these thoughts aren't chosen, using the vocabulary of sinful thoughts introduced by demons. But it's also clear that change is possible through prayer/meditation (not exactly identical to modern ideas about mindfulness).
I believe that our minds are much like Large Language Models. Our brains put together and combine and mix up sentences that on average have some benefit to us. We speculate to explore possible outcomes. We practice saying sentences within our heads and then explore their possible consequencees.
It is a random (but not totally random of course) process where one thought gives rise to new ones. I think that depression means being in an indirect loop of negative thoughts which amplify each other. Phychedelics might be a way to break out of such loops. But, I'm just speculating here of course.
> Ok like most of you I’ve taken psychedelic drugs. I’ve had bad experiences sure, but I’m fine now.
I guess people with really bad experiences don’t talk about them as readily as the lucky ones. I don’t know the scale, but there must be some selection bias at work here.
I'm a little ambivalent about this response. It sounds like you're describing invasive thoughts of some kind, though your description is vague. At any rate, despite the perceived negative effects, by your own account, it apparently spurred you to lead a healthier life; in other contexts, this is precisely the thing that is praised when it comes to psilocybin.
I had a profoundly difficult trip that affected me deeply. It felt eternal, and when I emerged, I could feel it in my head like some antimemetic parasite that fed off disgust and terror. I can still remember the feeling, twenty years later, if I try, so I don't. I had to learn how not to be influenced by it, and in doing so, learned about myself. And as I changed, because I was aware of what I knew, I knew when I'd changed.
Our selves are not immutable, steady states. Our experiences shape us. It's a lesson learned to guard that carefully and jealously.
Every general anesthesia I've had was basically "OK you'll start to get sleepy now" and then "ok we're finished" and zero awareness of any elapsed time.
Yeah, maybe don't take "very high doses". I've not done that. And not had any seriously bad experiences. Maybe like everything else is all about moderation?
It was 500ug of LSD mixed with probably 6 or 7 drinks of alcohol. Suffered serotonin syndrome for a few days afterwards.
Regardless I’ve heard stories of people having severe long term psychological issues from even relatively light doses, simply because of how their body in particular interacted with the drug.
That’s a massive dose and you mixed it with alcohol. That is in no way a responsible way to try out psychedelics. You are right that everyone reacts differently which is why you don’t take a very large dose mixed with other drugs.
Anecdotally, ayuasca quite literally saved my life and helped me tremendously when I was spiraling into a deep depression. Psychedelics when taken responsibly in a controlled environment under supervision can help a lot of people.
250ug of good acid is still a very high dose! 500ug is more like triple of a typical sane dose. milage may vary i guess but 300ug sent me out of this world
As I said my experience incurred more risk of severe long term side effects, but those are possible in any circumstance with any psychedelic with even a single, low dose.
To me, it’s interesting to consider the inflammatory aspects – the immunomodulatory effects of LSD and other psychedelics on one hand and alcohol on the other.
It’s well established but little-known that psychedelics have a very significant inflammation-reducing effect which includes drastic reduction of neuroinflammation. (I’m fairly sure that this is a primary reason why they work for depression and anxiety; There’s basically always elevated inflammatory biomarkers with these disorders. Stress is directly causative of neuroimflammation.)
> Suffered serotonin syndrome for a few days afterwards.
What sort of physician diagnosed you with Serotonin Syndrome? What symptoms did you describe to them, and what criteria/evidence did they use to arrive there? Were they able to use differential diagnosis to rule out other conditions?
Did you return to the same physician after the symptoms ceased?
Not OP, but the answer is probably what you expected. That being said, as someone prescribed multiple serotenergic drugs concurrently who was knocked on their ass by an errant Vit D dose, the symptoms are pretty obvious (and terrible) and do a good job of convincing one to “not do THAT again”.
I know, right? This is why we must be extra cautious with anyone's claim of disorder or disease, because just because someone thinks they are ill with a particular thing, doesn't mean that they, or even their HCPs have done due diligence -- modern health care is nothing like House or Doc Martin.
In fact, Wikipedia's fatal flaw is that we're forced to take medical claims at face-value when they're made by the subject himself.
Personally, my HCPs are very conservative and reluctant to diagnose -- particularly something they can't treat, and especially adverse, untreatable side effects such as "gynecomastia" or "tardive dyskinesia", etc. (Those could contribute to material grounds for lawsuits!) What physician in their right mind would formally diagnose "Serotonin Syndrome", other than one who's on the payroll of a tort/malpractice attorney?
It's interesting for me to balance a distinct tendency for Somatic Symptom Disorder (also shall never be formally diagnosed) with an impulse for self-knowledge, but an aversion to shitty "treatments" that invariably do more harm than good.
Very high doses used to be my jam. I have no real way to tell what the actual dosages were with LSD, but anywhere from 5-10 blotters was pretty typical for me, and had many positive experiences this way. Conversely, my 2 worst experiences were 2 tabs and 1.5, with the second being one of my least fond memories from my life.
I wrote out a lot more detail for this comment, but pruned to just attempt to make these points 1) generalization here is (generally) not very helpful and also 2) I've come to believe "set, setting, & dosage" are typically listed in that order because that is the order of importance.
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.
Conversely, for some people trying to fix depression with therapy and guided meditation can be a bit like trying to fix a Swiss watch with therapy and guided meditation. Everybody is different!
I agree, that taking psychedelics is likely not a good idea. But the analogue gives in my opinion totally wrong picture of the actual risks. Psychedelics, at least psilocybin, are quite harmless compared to almost any other substances. The reason for that is that they aren't very habit forming.
Personally I used psilocybin recreationally back in the days. Got once bad experience and ended up in a psychosis and to hospital. I got better in couple of days and long term effects were nonexistent.
Then I have couple of friends whose basic substances are just legal alcohol and cigarettes, and boy have they fucked their lives with those. It just takes a long time to do it that but psilocybin for sure does not lead to that kind of path.
There is actually a ton of incredibly fascinating knowledge about what psychedelics do – neuroimmunobiologically the effects are profoundly interesting. It’s a surprisingly sharp and specific instrument, certainly double-edged though.
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.
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.)
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.
Anecdotal but whenever I’ve been asked for this guidance (having been around the block, but not a shaman by any means) I ask about the person’s dreams. Do they usually remember them, how intense are they? More intense = start with lower dose (maybe .5g). Less so maybe start with 1 or 1.5g. Of course this is subjective and relative but a rule of thumb that has worked reasonably well.
For frequency, that depends on a variety of factors I suppose.
I don't plan on ever taking psilocybin- but why dreams?- Asking cause I almost never remember any- unless I wake up at a weird time- or sleep in a weird circumstance.
Is it indicative of anything?- I sleep really well, never had any issues with sleep- and wake up well-rested. Is it better to remember more dreams?- if so what are the benefits and how to go about doing it?
I’d love to have an answer to this! As I said this is anecdotal, based on many years of experiences with friends, and the ones tending to have more vivid dreams seem to have more intense trips given equivalent dosage. It became a bit of a pet theory at some point so I ask about it. I wouldn’t be surprised if there’s some confirmation bias or something like that at play, but given the kind of hallucinatory nature of dreams I can also imagine some sort of linked mechanism.
I also rarely remember dreams and despite occasional exceptions wouldn’t consider most of them vivid. So I tend toward heavier dosages :)
Note that most of the responses you're receiving, while accurate, are in terms of units of dried cubensis mushrooms, not pure psilocybin. A fresh cubensis mushroom weighs about one-tenth its original weight once it's fully dried, and when dried they usually contain about 0.7-1.0% psilocybin by weight. So 2.5 grams of dried mushrooms will contain about 25mg of psilocybin, which is the "25-mg oral dose[] of psilocybin" given in the study under discussion.
A practical approach is to take about 1.25 grams of dried cubensis, wait about an hour to see how you feel, then try another 0.5 grams if you're up for it, and then another 0.5 in half an hour. By that point you'll have ingested enough to notice effects for sure, and you'll have confidence what your personal right dose is.
Beware of tryptamine tolerance: wait 2 weeks between doses to reset your sensitivity.
Each mushroom contains a different amount of psilocybin. You can calibrate a batch by grinding them all up at once in a coffee grinder and trying a sample. (Always be careful taking powdered mushrooms that someone else has ground up, because you don't know whether anything else has been mixed in.)
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.
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.
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.
The 2018 Hemp Farm bill gave the balls back to the citizens that the 2013 Analag act neutered.
Seeing mushroom extracts with all the alkaloids included besides psilocybin at gas stations may be a temporary point of stability until I can go to the "21+" store in 2030 to get my preferred arylcyclohexylamine and phenylethylamine variant.
From what I understand, those “magic mushroom” edibles sold in head shops and gas stations are amanita muscaria derived, which is a completely different psychoactive substance with different alkaloids. Toxic to the liver too, in ways that a cubensis is not.
I was aware but I should know to put disclaimers in drug posts on HN at this point, as others may not be; thank you.
That being said, it did have an uncomfortable but brief 'burning/cleansing' feeling reminiscent of Lyseragmides that that most tryptamines / 4-aco-DMT / penis envy / cubensis / 5-MEO-[xxx] did not, and more visual distortions with notably less headfuckery / low body load.
I recommend a single try; the tolerance seemed to eliminate effects nearly immediately.
Northern shamans drank reindeer urine after the animals had eaten amanita muscaria. Passing through the animals reduced the toxic component but left enough alkaloid to trip balls. Maybe the gas station edibles have removed the toxin.
Geneva is home to the only Swiss hospital offering psychedelic-assisted therapy. [0]
Also, Peter Gasser, a Swiss therapist acquainted with LSD during the 1988-1993 window, was granted approval to carry out the first controlled study of LSD-assisted psychotherapy in more than 40 years. [1]
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.
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.
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.
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.
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.
> "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?
> A more holistic approach to health care would be beneficial.
I've commented on this elsewhere, but with psychedelics in particular we wind up in a weird space around our normal approaches to health - for instance, there's a lot of effort right now on finding the chemical mechanisms by which psychedelics affect mood, with the goal of creating substances which have the same impact on depression without the phenomenology of the trip. My suspicion is the trip is the treatment, or at least part of it - that the experience of being in an entirely different mindstate, of reacting to the world in a fundamentally different way using different mental pathways for several hours - is a core part of the treatment. Medicine has a bad habit of ignoring the patient's lived experience - to look at the patient broadly as a mechanism, and particularly as a collection of mechanisms, and to see things like hypertension* as something to be treated with a chemical offset and not a reflection of the full factors of a person's life. My hope is that the psychedelics will help us recognize a paradigm shift here (like, in data leading to changes in practice, not just in their normal way), but I think they've still got too much of the taint of the hippie on them to really be taken seriously.
* I'm using hypertension as just an example of a particular ailment, I'm not making a statement on the treatment hypertension in particular.
> A more wholistic approach to health care would be beneficial.
Maybe. My personal experience has been that those "negative symptoms" were in fact the entire disorder. I didn't need purpose or depth. I needed to not be so sad that I couldn't function. I needed to be able to hold a coherent thought for 5 minutes without getting stuck into a negative spiral of self loathing.
I want "purpose" and "connection", but those things are what everybody on earth are looking for. The search for those things is the _stuff_ that life is made of. I needed help to get back to a place where I could pursue those things. Pursuing them is my life.
> 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.
> Many people here are speaking from experience. I trust my own judgment over some knob in the FDA that is steeped in a culture of drug control.
Let me paraphrase this:
Many people here are parroting stuff based on a sample size of 1, who lived to tell the tale. You trust your own judgement based on those people before the rigorous safety and effectiveness studies for the FDA, on a whim that the FDA approves or rejects drugs based on their... ? Culture of hating recreational drugs?
The FDA exists to tell you, a free individual, what you are allowed to put in your body. It has been a very long time since the FDA has been about safety only. It is wholly captured by business interests in food and drug industries. So yes, they, and the government culture as a whole, hate recreational drugs that they don't control in some way. No shooms for you but drugs that cause suicidal ideation are prescribed by the millions.
I am wary of people "looking out for your safety" when there is financial incentive to do otherwise.
And psychiatric drugs don’t ever make things worse? As someone who was severely injured by FDA approved, scientifically validated medications, I’d say some healthy distrust of a corporate-captured bureaucracy is warranted. Remember, OxyContin was FDA approved. Did the FDA ever launch an investigation into how they allowed that disaster to happen? No. They didn’t so much as say “whoops”.
You have to put effort into making an experience with psylocybin meaningful and helpful. It could go wrong very easily, especially for those who are in a difficult situation or headspace. (Speaking from experience.)
As for SSRIs? Safe, effective, with a handful of annoying side effects. Straightforward to use, low potential for misuse, requires sustained use for any intended effects. A doctor who already has familiarity with a patient's mild or moderate symptoms of anxiety or depression may very well just prescribe one if asked and if not contraindicated. Not that you should randomly start popping Prozac, but it's unlikely to hurt you if you did.
Ask your doctor, try the things that doctors currently believe are most likely to work first. If for whatever reason you choose to go beyond the current medical consensus, please stay safe and keep your doctor up to date.
I'm not claiming they don't. Everyone experiences SSRIs differently and it's common to shop around until you find one whose side effects impact your life in a more tolerable way.
That's in contrast to psylocybin, which has substantially more serious potential acute side effects, ones that are more difficult to understand and treat should they occur.
I'm not saying psylocybin is unsafe or that SSRIs are always preferable. But if I'm asked to compare their safety? The choice is obvious, weight gain notwithstanding.
You were clearly implying they don’t when you downplayed all SSRI downsides as “a handful of annoying side effects”.
Weight gain kills. Suicidal ideation also kills many people when they start SSRIs. People have killed themselves because of permanent sexual dysfunction caused by SSRIs that never went away after stopping the drugs (and yes, this is a known possible adverse effect listed in the official prescribing information).
I don’t think the choice is as “obvious” as you’re making it out to be.
I guarantee you the number of people who have died from SSRI misuse is higher than the number of people who have died from psilocybin misuse. I'm not referring to things a person may do in a given state, I'm talking about effects from the drugs themselves. I'm not aware of a single recorded person who has taken any dose of psilocybin, and died from "psilocybin overdose". While it may be uncommon, it is possible to overdose on SSRIs.
Sure, psylocybin won't kill you, but the threat of inescapable psychological distress is real. Maybe it's less likely if you aren't predisposed to psychosis, but you can't easily know for sure that you're not.
And yes, it's possible to misuse SSRIs, but taking an obviously oversize dose is still often a treatable situation. Combining them with depressants I think is a degree of misuse that is incomparable.
While fishing for that right dosage of SSRIs you have a person with new boughts of mania and suicidal tendencies where there's no clarity on how to stop the experiment due to the complexity of blood level accumulation.
If SSRIs started as illegal drugs, with i.e. people starting them dodging medical supervision, I think the system would be telling us they are insanely risky and well beyond many scheduled drugs.
A prescribing doctor will not magically know the precise amount of an SSRI a patient should be taking, or which one to take. For most patients, finding the right drug and dosage is a process. And just like with psilocybin, no one would want to take a random amount. Like with any drug, a person would want to be informed and have proper guidelines about dosage from the start.
Page 19 onward has the charts. What do do we find at the very low end in terms of chronic and acute toxicity? Shrooms (“paddos”) and LSD.
It always blows my mind how anti-drug people will do a handwavey gesture to the authority of institutes like the FDA, but never actually check up on what actual research says.
> As for SSRIs? Safe, effective, with a handful of annoying side effects.
Except the multitude of ways you can put yourself into a serotonin coma.
I agree with your assessment that (first) use of psychedelics should be under proper guidance. But what you refer to, “going bad”, can sometimes be a traumatic past experience that people have stuffed away and by surfacing and processing it they can move past it. It’s not always meant to be kumbaya and flowers.
I'm not saying psylocybin can't be used safely, nor have I made any claims about its relative toxicity or harm relative to other scheduled drugs. If you're arguing anything else, I don't think that report says what you think it says. As for my position, I live in SF, it's decriminalized here, I support that. So there's no need for your rude presumption that I find it generally unsafe.
I'm also unfamiliar with the dose of SSRIs that would send you into a coma, but I'm fairly certain it's shockingly large. Happy to be informed otherwise.
edit to reflect parent edit: yes, I'm aware that breakthrough experiences can be helpful. I'm also saying they should not be your first resort.
> I don't think that report says what you think it says.
The report also speaks to personal, social and populational damage.
> I'm also unfamiliar with the dose of SSRIs that would send you into a coma
Its not the SSRI itself, but rather anything that messes with your reuptake can put you into some deep problems. And of course the bog-standard grapefruit+medicine interaction.
> I'm also saying they should not be your first resort.
My point was that if we are talking drugs, yes, treatment with psilocybin should definitely be higher up the list than SSRIs. SSRIs would most likely be for life, daily. Psilocybin could be bi-annually or perhaps even as spot treatment only.
> So there's no need for your rude presumption that I find it generally unsafe.
Apologies for coming off too strong. I just feel that, reasonable as it is, the “let’s all just take a minute” attitude gives too much ammunition to conservative hoohas to stymie these alternate treatments for another few decades. Imagine if marijuana had been more accessible to people like this in the 80’s-10’s:
> > You have to put effort into making an experience with psylocybin meaningful and helpful. It could go wrong very easily, especially for those who are in a difficult situation or headspace. (Speaking from experience.)
> What do do we find at the very low end in terms of chronic and acute toxicity? Shrooms (“paddos”) and LSD.
Breaking your mind doesn't count as toxicity. You're not responding to the point you tried to refute.
It’s rather difficult to “break your mind” on psychedelics.
Unless you either A) already have a predisposition to something like, say, schizophrenia, or B) take stupendous amounts, you’ll be fine. And vis a vis point B, in the older days there were people who did multiple LSD hero doses, without frying their brain.
Definitely psilocybin. For instance, if you take psilocybin and then spend some time in a cow slaughterhouse house, you might go crazy. The same wouldn’t be true of SSRIs.
I really wish we would retire this chestnut already. As if there’s a reasonable grownup option here and everything else is playing with matches.
No it’s not the best thing to do to brave huge waiting lists, call a hundred providers none of whom are taking new patients, pay a fortune out of pocket, and/or be faced with a distracted impatient person stuck to their screen who has 10 minutes for you.
That's not clear cut. There clearly exist plenty of combinations of "situation + physician" where this is not the best thing to do. To claim otherwise may as well be religious dogma.
At the very least, consulting with one or more physicians gives more data points than you would otherwise have. If your goal is to know more, having other opinions is pretty fundamental.
Doing a rain dance and concluding that it doesn't help also gives you another data point. Praying as prescribed in 50 different religions a whole lot more data points. And so on.
I'm not a nut screaming "It's all a scam, don't participate in modern healthcare!". Just noting that it's complicated, and the idea that going to a physician is always the best option should receive more scrutiny, because it's not black and white.
I'm sorry, but how is trusting a person who dedicated 10+ years of their life studying/practicing this, and relying on rigorous safety and effectiveness research of drugs religious dogma? Are you sure you know what religion is? Are you sure you know what science is? Are you just trolling?
If you actually read the effectiveness and safety research with a critical eye, you would realize “rigorous” is often the wrong adjective, whereas “cherry picked” to the point of “fraudulent” is often more in line with reality.
Case in point: 50,000 people died, with about 5 times as many suffering life-changing serious adverse events, from “rigorous research” on the safety of Vioxx. Yes, it has since been pulled from the market, which FDA apologists often construe as “system working as designed”. No, it isn’t, even in the least, when you go into the details.
Also: Purdue and OxyContin.
Regulatory capture of the FDA is decades old at this point. Ignoring that is not a rational or healthy position.
I don't know, why don't we ask my colon? Oh, wait, we can't. I was prescribed accutane, subsequently got ulcerative colitis so bad that they had to remove the organ entirely. The surgeon said my colon was literally falling apart in his hands as he took it out. Blind deference to authority of doctors lead to this situation. They do not always make great decisions, especially if there is a financial incentive for them to do otherwise.
Do you not know anyone who has spent many years of their life doing something and are still rather poor at it? You probably do. You may even have such a skill yourself - I certainly do!
that's easy to say when you forget about the state of healthcare.. everywhere, actually. I was going to say the US but in other countries it's not like you can just pop in for a chat about taking shroomies, either.
I'm not sure having a ten minute meeting with a stranger who has a PhD in internal medicine is going to yield useful strategies for curing the existential dread underpinning your depression whether you're there to discuss getting zonked on LSD or something more "traditional" like Xanax
> it's not like you can just pop in for a chat about taking shroomies
You sure can just pop in to discuss options for your crippling depression though? And sorry, I do indeed live in a country with a functioning healthcare system, not the US.
In the US normally you talk to a therapist (not a doctor) or psychologist (not a medical doctor) about your depression at length, and then if you're deemed sufficiently depressed you get a short consult with a psychiatrist (finally a doctor) to prescribe medication. This is when you would theoretically finally be able to bring up shrooms, and your psychiatrist will laugh at you, write an Rx for an SSRI, and you'll see him next year when the Rx expires
I'm not sure how it is in most countries but I'd expect the biggest difference is that it will cost you money in the US, but I've read many many horror stories about people waiting many months to have only a short chat with a physician from other countries. The lack of time available to spend taking to physicians seems to be a problem in other places too
my point is that consulting a doctor with random questions isn't a simple, casual thing people can easily do in most places. in most places you have to plan ahead and either wait a long time for an appointment, and/or there is a cost barrier.
if you have examples of countries where people are able to get to know their doctors on a personal level and can afford in time and money to talk to their physicians for more than a few minutes per year, please link them below
> You sure can just pop in to discuss options for your crippling depression though
To get a prescription for one of the the handful of drugs are are available and are considered to be effective. What else can you learn by just "popping in"?
> with a functioning healthcare system, not the US.
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).
The idea that doctors aren't constantly "off base" and must be deferred to uncritically is pretty terrible.
For example, it took literally two decades after it became well known that peptic ulcers were mostly caused by bacteria for the medical community to embrace giving anti-biotics for GI pain. To this day, there are still many American doctors who don't actually know about the Nobel Prize given in 2000 for this discovery, and claim it's "stress" and tell you to go home. Some claim they "know" but than try to "change your gut PH" and still refuse to give antibiotics due to "superbug" risk.
This is a "small" thing (GI pain is not small to those who have it) - but if the doctors are screwing up such a small thing institutionally, what else do they mess up on?
One is travelers sickness. Doctors in the USA do not want to perscribe front line antibiotics for it because of fear of superbugs - but they'll uncritically go eat their lunch at a McDonalds that same day, where they consume meat bathed in antibiotic slop which is more likely to contribute to superbugs then the amoxicillin that they didn't give you would have.
Or what about right now, when it's become clear that Ozempic is literally a super-drug. Every doctor on earth should be trying to give that stuff to literally anyone.
I can go to "third world countries" with deregulated health systems and get infinitely better care that I have real control over for on the orders of 1 USD (that's how much it cost for me in Thailand to get front line antibiotics for travelers sickness INCLUDING THE DOCTORS VISIT!)
Why do we still sell Neosporin despite doctors wanting it off the market (also for risk of superbugs)? Why do few people in America use Providone-iodine for wound treatment despite it being by far the best solution scientifically for it (and it stains yellow)? Maybe it's because we're stupid. There really aren't better explanations.
What about Circumcision? I'd straight up put doctors who do it in jail and many European nations would do the same. American doctors think circumcision is just fine, and long, deeply bitter swaths of medical ethics journals are dedicated to fighting over this again and again.
Or what about the widespread disagreement over even basic stuff like digital rectal exams? There's no agreement on if they are worth it because often sticking one's hand up the butt of an old man does more damage to them than finding out that they (like everyone else at old age) have benign prostate cancer?
Doctors in America have not earned their position of deference. The scientifically minded on HN who do their own research can and often do know how to treat certain conditions better than white-coats.
Probably not…the question is, does Psilocybin have a higher incidence rate of users suffering episodes of severe depression or psychosis than, say, SSRIs. Amongst all the “spiritual” drugs, even counting THC, Psilocybin is the most well tolerated—even so, SSRIs tend to still be very safe, even if they are not very effective.
The best thing to do is to consult with a physician on this matter, еven if side effects, drug interactions and precautions are readily available and cardiac arrest and death are among them. Idk, is this worse?
What would be the point of that? I'm pretty certain that almost any physician would tell you not to consume psilocybin (especially if you are suffering from mental issues).
My suspicion has always been the majority of adverse reactions have related to improper dosing.
Anyone can have a horrible response with too high of a dose yet with self-medicating theres no sure way to know the amount of medicine you’ve ingested even if weighing.
> 'He added a word of caution for therapists that "psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this."
The long-term consequences of trying to avoid such issues seem considerable, e.g. it might lead to schizophrenia if people try to wall off parts of their memories they find intolerable, though that's just speculation at this point.
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.
> 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.
> 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.
This is true of most if not all drugs / studies. That is, the drug gets "credit" for the placebo effect. Sure they took the meds, but that's correlation in at least some. That is, in some the drug did not actuay work but they still get to benefit from the placebo effect.
I rarely see this discussed. I'm not sure why (short of actual cellular test showing it was the drug that did triggered the success some of the success even in the group taking the real meds is still the placebo effect).
This might not be ethical, but given a psychedelic naive population, I wonder if the control could be given a non-serotonergic psychedelic such as salvinorin A. There would definitely be a noticeable effect, but for someone who hasn't studied the effects of psilocybin, they may not realize it. The downside is that in order to keep the duration similar, you'd probably have to administer the salvinorin using an IV drip, and a six hour salvia trip could quite possibly be too traumatic.
It might be nice to also have a non-psychedelic non-sari as well. Right now a patient could use whether they tripped or not to determine exactly which treatment they received. But if you had the full 2x2 design of {drug has trip, drug has no trip} x {drug is supposedly therapeutic, drug is non therapeutic} the existence of a trip wouldn’t reveal their exact treatment
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?
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...
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.
I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocybin vs escitalopram.
This is already a problem for most psychiatric drug trials; studies have found that most people can tell if they’re on an SSRI or in a control group, since the side effects are pretty noticeable.
There is evidence that this skews study results, to the point that some scientists believe that SSRIs may only be “effective” because the obvious side effects make them a good active placebo.
Being blinded isn’t some gold standard. For example we know exercise leads to good health outcomes from unblinded studies. Every study on fitness ever done is unblinded and we consider these results to be a ground truth.
The randomized controlled double-blind study is a gold standard. It solves for so many different biases. Without it the burden of proof is higher. Luckily, the evidence that exercise is healthy is so overwhelming that we have a scientific conciseness.
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?
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.
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.
> There's no one to trust more than a good friend to be there for you when the ride gets bumpy, not some guy in a suit doing it for the money.
I couldn't disagree more.
Your good friend most likely doesn't have the slightest idea how to handle things if your trip goes south. Especially when they're on their own "ride". That's not to disparage anyone, but just to state the fact that there is training around these things that comes from lots of experience.
And therapists are not "some guy in a suit doing it for the money". You don't get rich doing psychotherapy -- you do it because you genuinely want to help people. And never in my life have I seen a therapist in a suit.
This isn't to say that every therapist is great or that every friend is terrible -- just that the relative success rates of being able to help someone on a bad trip, both during and after, are going to be a lot higher on the side of trained therapists. Because of the training.
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 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.
I don't think you've really considered the incentives either.
The system has as much interest in curing your depression as it does curing obesity. Long term, these conditions are very costly. It takes people out of peak condition, reduces labor pool, increases number of patients taking up resources at hospitals and doctors offices, and so on. A system which encourages these things is a failing one, as taxpayer costs would only continue to balloon.
Additionally, since the thread is about psilocybin, people would still be filling up prescriptions for those.
Also, self-medicating is also very costly. Not only to the system, as people often wind up in hospitals due to laced products or incorrect doses (see marijuana in a lot of states where dealers really aren't concerned about quality), but also to the individual. People are spending absurd amounts of money on vitamins and mushroom teas and all that in hopes it helps, but rarely is that the case due to these categories not being strictly regulated.
I think your argument is as valid as the one you're responding to.
>The system has as much interest in curing your depression as it does curing obesity.
Ironically enough, the system hasn't cured obesity (if you believe obesity is primarily caused by a poor environment) and seems to instead to be headed towards managing symptoms by hacking our hormones and brains with semaglutides, etc. But at least you can work.
If you use a similar train of thought applied to depression - we're now in a situation where something like 50 million Americans are on antidepressants or antianxiety medication. 1 in 6. This is also treating symptoms and putting people into a state of being able-bodied without being so well as to remove their dependency on the drug. But at least you can work.
So I think the original idea fits with the concerns you outline. Mass producing a few drugs to keep a majority of the population able-bodied might not be that much money in the big picture.
I'm not a firm believer in this theory, but I can totally believe an overly complex system with poor incentives and no absolute oversight can lead to these outcomes.
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.
I get the impression that there’s misalignment on what “the system” is to each commenter here. One side views it as the larger society and the other as the pharmaceutical industry.
> society and the other as the pharmaceutical industry
The market is huge and executives usually care much more about short-term (or at the most medium-term) growth. A company that actually found some magical cure for depression they would have no reason to not undercut their competitors and still make massive amounts of money even if that would destroy their target market would disappear over the next 10-20 years.
Also aren't pretty much all the most popular antidepressants and related drugs relatively very chip. Nobody is making that much money selling SSRIs. Why would pharmaceutical companies forego hundreds of billions on purpose?
>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;
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.
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.
"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.
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.
If someone is unfamiliar with psychoactive drugs, I would suggest they eat a single mushroom cap in a safe, private, comfortable environment and with another person who has some experience. I think it is a more pleasurable and worthwhile experience than marijuana, which can actually be more intense and is more prone to generating anxiety and paranoia. There's lots of resources online and there are communities in a lot of cities that advocate mushroom use.
Mescaline is like the angry lover version of mushrooms. I did it once, two years ago to understand why it has been used, traditionally, as the baseline for comparison for psychedelic substances, and it was enlightening; it is certainly a tasting menu of the classical psychedelics, having at different points in the experience the flavor of stimulants, LSD, mushrooms and finally something all its own, but it is also much grittier and less loving than mushrooms.
Mescaline is _rough_. And honestly the "you are done with it before it is done with you" thing is 100% true, it is also very long lasting.
Never tried it. Seems like it's vaguely hard to consume safely since it is tied to shaman woo culture overseas. Supposedly there are sessions in the bay area, but I'm not cool enough to know people who know about them, or for that matter the other things I'd like to try.
I have a plan to try it, DMT, LSD, 2-CB and 5-MeO-DMT before I'm 60, so I guess I'd better get cracking as that isn't far away for me.
I've known far fewer people who have taken it. Unlike mushrooms, I have heard stories of prolonged and difficult trips that sound much more challenging and arguably dangerous than a average-dose mushroom trip.
As someone who has personally dealt with mental health issues I attribute to use of cannabis, I agree with the underlying sentiment here.
The people in this thread saying things like, "they wear off" or dismissing clinical treatment for depression as "suits ripping people off" are delusional and embodying bad stereotypes. Just because you and your bros took mushrooms, had a few laughs and carried on "working hard on saas" or even had a beneficial, religious-type experience doesn't mean that there aren't also risks or that everyone will have a similarly beneficial experience. It's been known for decades -- both empirically and scientifically -- that psychoactive substances can surface latent or bring about psychological issues (e.g. cannabis and schizophrenia) in some people.
Now, I'm not against use of these substances medicinally or recreationally but to pretend like there is no risk and that they're a one-size-fits-all miracle cure is reckless, naive and dumb. As mushrooms and cannabis become more widely available and more powerful (in the latter case), I suspect we'll be hearing a lot more about this class of issues in the coming years.
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.
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).
> "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.
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.
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.
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.
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."
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.
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.
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.
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.
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.
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?
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?
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.
What you're describing sounds very much like the impact ketamine has on the default mode network (DMN), which plays a central role in your sense of self and how you process thoughts about yourself and the world. The DMN is typically overactive in conditions like depression, leading to persistent negative self-reflection or rumination.
Ketamine temporarily disrupts or disintegrates the activity of the DMN, which is likely where the sensation of "disintegration" or "ego death" comes from. This can feel like a profound loss of agency, as the very part of the brain responsible for your sense of self is being deconstructed. The disorienting part—being left with fragments of yourself—is also consistent with how the DMN breaks down, exposing subconscious thoughts or patterns you may have repressed or forgotten.
But this isn’t just a random break—it’s part of why ketamine can be so therapeutic for some people. By breaking the DMN's rigid structure, it allows for a kind of mental reset, where you can reorganize those "pieces" in new ways, often leading to the clarity or "AHA!" moments you described. The months of renewed understanding and hope after the experience fit well with ketamine's fast-acting antidepressant effects.
That said, I understand the hesitation to repeat such experience. While it can be transformative, it can also feel traumatic, precisely because it’s messing with such a fundamental part of how your brain organizes reality. We’re still in the early stages of understanding this, and while it can be deeply healing for some, it’s definitely not something to take lightly.
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…
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.
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...
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.
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.
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.
> ... burnout-related depression (person worked normally their whole life but is suddenly just empty of energy and does not look forward to anything with joy) ... existential depression and anxiety that is driven by pathological self-focus (not egotism, but inability to stop focusing on one's own inner states)
Is there any rigorous operationalization of these concepts, that might be explored in further studies? Unless one can be found, these fuzzy, heavily qualitative descriptions are unlikely to be helpful for future researchers.
It's counterintuitive to me that a more specific concept/subgroup of a phenomenon would be less useful than a larger catch-all category. Is the self-rated questionnaire depression scale used in this study a good "rigorously operationalized concept"?
We are successfully treating people with this exact kind of indication/operationalization with real success already. For instance, the indication criteria for ECT basically follow the "burnout profile" I described above, with the addition of "treatment resistant to therapy and medication," and it has shown by far the best effectiveness for that kind of depression.
I completely disagree that it's not possible to operationalize the concepts above, for instance with standard BDI or MADRS, supplemented with a ratio with a cutoff to indicate a large fall in everyday functioning. Like an extremely large fall in Global Functioning Scale (GAF) localized to a distinct and pattern-breaking period in a person's life. If you think that these concepts are fuzzy and qualitative, I really hope you have even greater criticism towards this study, not to speak of concepts like anxiety, trauma, and ADHD, which are completely off the rails when it comes to diffuseness and subjectivity.
But even if you are right, that burnout-depression and existential anxiety are not possible to study because of their vagueness, it still would not make this study helpful as it's presented. Or am I mistaken? Do you think it's a good and helpful study, whose implications I should fight for in our clinic? And would I see a marked improvement in our patients, compared to SSRIs for the "Depression" group?
I am willing to admit I am wrong. The only goal is to actually help people.
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?
>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.
They got 'matched' support, which reads to me as 'equivelent': "Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET)."
>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?
This is only the follow up portion, and as secondary measure at 6 weeks. The original study (https://clinicaltrials.gov/study/NCT03429075) says the primary measure was; "Change in blood oxygen level dependent (BOLD) signal during fMRI in response to emotional faces during an emotional faces paradigm done inside the fMRI scanner." at 6 weeks vs baseline.
>The results are based on a grand total of 25 people in the psilocybin group and 21 people in the SSRI group.
Statistical significance is based on sample size, and is independent of population size. Let that sink in, doesn't matter if your population is 100K or 8 billion, when you sample you are trying to understand the probabilities in your sample, not in the population.
Therefore, (think about the birthday paradox, doesn't matter how many people in the world, a few dozen in the room with you is an adequate sample), it should not surprise you that statistical significance is achieved through a much smaller sample size than most non-statisticians have intuition for.
> few dozen in the room with you is an adequate sample
It's not, though? Unless you're fine with a very high margin of error... Also the sample in studies like this is hardly ever close to being random anyway.
> it should not surprise you that statistical significance is achieved through a much smaller sample size
Sure... just with a very low confidence level.
Margin of error only occurs when you expect high variability and a very large population of measurements. When the set of potential measurements is of size 2, having enough statistical power can be achieved with very low sample size. Anyways, many results have survived stage 4 analysis (real world, observational, administrative documents sourced), even when their OG sample size is relatively small.
Statistical analysis in psychology is traditionally very poor, because there is an exceptionally high amount of variability. This is a known problem.
No, psychology studies have been traditionally very poor because most of the theory was literally out of someone ass, without proper design. Newer studies have been shown to be very robust, public freakout notwithstanding.
Newer studies [0] show us that
a) p-hacking is still alive and well in the psychological community.
b) p-curves are not sufficient for detecting this.
That isn't a lack of proper design. It's a case of statistics being abused to show significance when there is none.
[0] https://psycnet.apa.org/doi/10.1027/2151-2604/a000383
>Therefore, (think about the birthday paradox, doesn't matter how many people in the world, a few dozen in the room with you is an adequate sample), it should not surprise you that statistical significance is achieved through a much smaller sample size than most non-statisticians have intuition for.
This response on the supposed the lack of importance of a sample size is completely wrong on just about every claim. The parent comment had a valid point. Just because a population may fit a certain distribution, does not mean that any given sample size will also fit that distribution. Samples are used to ideally create a representative group of a population, that is smaller than the population. However, the sample size required to come close to a representative distribution can vary between populations and variables being examined. Also, using the birthday paradox is a terrible example and has nothing to do with statistical significance, as the so-called birthday paradox is just a simple function.
Except that sample size doesn't matter if the set of potential results/measurements of the dependent variable are very large. Someone pointed out that you can demonstrate that alcohol impairs executive functions, balance, etc. with a very small sample size, because the effects would be so large and evident that your statistical power would be. On very large variance, where the results are dichotomous in nature (can a subject walk straight in a 10 meters line, without walking outside: yes/no) can have a very small sample size.
Use this calculator, set options to: two independent groups, dichotomous, group 1 = 90%, group 2 = 10%, incidence, enrollment ratio = 1, alpha = 0.05 and power = 80%. The sample size is 10, 5 for each group. https://clincalc.com/stats/samplesize.aspx
That other comment on alcohol is by the same guy that made the comment that I responded to here. The same issue there is that result reliability can be influenced by the effect size of the variables being tested, but this still is far from a guarantee that the results will generalize, which is more likely to be an issue with a smaller sample.
An issue with the comment I previously responded to, as I mentioned above, is that they made it out as if a small sample size could be reliable to determine a reliable statistical significance irrespective of the variables under study and tried to prove this by using an absurd analogy between statistical significance and the birthday paradox. The problem with their attempted point was that it didn't even respond to the comment above it, which pointed out that a high statistical significance is not a guarantee of reproducibility, especially with a low sample size.
Sample size only matters for statistical power. After certain point, the diminishing returns will fall of a cliff. Lay persons seems to have mistrust of seemly small sample sizes, but they need to understand that doubling the size of the study only improves statistical in 5-10% for dichotomous studies. If we mandated a bigger sample size without taking into account why it's relevant and how it's calculated, it will make every study cost prohibited.
The issue your parent comment raises is that this random group may not represent someone that's trying to evaluate what techniques can help them, regardless of the statistical significance within that group. It makes me sad that they introduce other random variables, as incontrovertible evidence of efficacy could help a lot of people!
except it was completely non-specific about what those flaws might be, simply saying "sample is too small" when the sample is not a priori too small for a properly designed study of something that has "noticeable" effect. For example, "does alcohol get people drunk" is not hard to show on a sample of 10 people.
A larger sample size isn't inherently better, but if a large sample size from a diverse enough pool of people can be used to eliminate and/or identify confounding variable and distortions.
This comment is a shining example of the phrase "not even wrong".
Just the first line alone "Statistical significance is based on sample size, and is independent of population size", was bizarrely silly in its description of the use of sample sizes, before they even got to their nonsensical analogy to the birthday paradox.
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?
> 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?
They try to make for no comorbidities and and for MDD that is pretty rare. It also means that we’re often studying rare configurations compared to those commonly seen in actual practice. Statistics doesn’t like confounding elements and humans are very confounding. So either you get “bad” statistics, or you get “bad” data. And why you have front line drugs that only have a helpful effect for 33% of people.
Just to add one minor detail to this very good explanation: even if you could find 500 participants matching the criteria instead of 50, you wouldn’t want to “waste” all of them on your first study design.
Its expensive. Statistically speaking its really not that small. You can always argue p hacking but these are always useful as a means to do further research
> If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"?
Those are design descriptions.
Double blind means that neither patient nor the one administering the treatment knows which is which. Randomized only means that each subject is assigned randomly a treatment group. Controlled trial just means that the study design made sure that other variables that are not under experiment are also under control. Nothing about this preclude actions done to the subjects nor sample sizes.
Often you’re not allowed on your medication for any of your other health issues.
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.
That's not generally how drugs work. There's wide margins on how much dose is required for clinically significant results. Not only is the 110 pouns petite woman taking the same dose of aspirin as a 400lb elite powerlifter, but the effects can't be quantified in high resolution. The woman can't say her pain was 5% less than the powerlifter, and they can't say their pain was 5% more.
This doesn't sound very helpful
I mean it sounds like a way to trick people into letting a giant company build a surveillance system, and I imagine aliens observing humans in this moment in history might conclude that's what we want, but for science or the benefit of the people "surveyed" it's mostly downsides
TBH there's no way to have a double blind trial of drugs like psilocybin (Scott Alexander has written a little bit about this [1] with respect to controlled trials for MDMA), for any reasonable dose size of psilocybin. Both the patient and the person administering the drug will become very aware, very quickly, if they're in the psilocybin group.
1: https://slatestarcodex.com/2017/06/05/is-pharma-research-wor...
Unsurprisingly, the way around it is to introduce a third treatment or fourth, with classical psychedelic 5-HT2 action. There are a few such choices and some are also registered antidepressants, one being DXM/bupropion, another being an ergoloid derivative or a psychedelic amphetamine like DOM.
But then you need to run a trial in a hundred or two hundred N.
This is wrong. You can absolutely dose psylocybin at levels that make a meaningful difference in experience (certainly enough to have an anti-depressant effect) without “tripping” or being in any way impaired. For many adults, this will be around 100-200mg of psilocybin.
It's not a question of impairment, it's a question of whether you come to some determination of whether you are in the control group or not.
Microgram, not milligram, of psilocybin. 100mg of psilocybin would be about 50-200 grams of dried cubensis mushroom.
There have been studies on microdosing, but it’s also valuable to know what happens at perceptible doses as well. It’s certainly a different experience.
Therapy is such a wash statistically that I'm not particularly confused or concerned by that, and everyone that has ever taken psylocibin knows the results are typical.
It’s kinda interesting you say that because studies show that SSRIs are not much better than placebo for treating depression, and that therapy plus SSRIs is the best treatment available right now.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592645/
The article states that both groups received psychological support though. The only mention of 20 hours I find in the article is as an option to psilocybin. Does the original research article say something else?
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.
Thanks for sharing this, you’re not the only one. I have a close friend who tried LSD as a last resort to get the best of his severe depression and suicidal thoughts (after being on SSRIs for his entire life) and just one session completely removed his suicidal thoughts for months. After this experience he repeats this whenever he feels the dark thoughts are coming back and it always curbs them down almost completely. It’s mind-blowing how well it worked for him.
just consider, if it's so powerful in adjusting his brain, it's probably equally powerful in adjusting anybody's brain, and what if your brain doesn't need adjustment? there's no reason to think it's "idempotent" so to speak.
https://en.wikipedia.org/wiki/Idempotence is the property of certain operations in mathematics and computer science whereby they can be applied multiple times without changing the result beyond the initial application
My experience with psychedelics is the following: they shift your perception of things temporarily. The way the "adjustment" works is that you are able to "see" and "touch" experiences you could not before, because they would have annihilated you. They open a door to re-living things and re-processing. Hard for me to see that you would come out of that "broken", if there's nothing to process your trip will be a pleasant high.
Which is not to say that psychedelics (LSD, 2C-B, Mescaline, Psilocybin) are not powerful stuff and that they allow for mental states that would be unlivable otherwise (clinically that would be schizophrenia or something like it). I do believe that their therapeutical and recreational benefits do outweigh the drawbacks though. There must be a better way to handle this than Schedule-1'ing the whole bunch.
Powerful they are indeed. Depends on general personality, current mental situation, dosage taken, environment and/or people setting up the vibe. That's why I think they should be 100% available but 100% only under professional supervision, who has chemistry and skills to stop the trip gracefully if needed.
I've only ever done them (mushrooms) alone, mixed with fresh lemon juice that somehow makes them more intense and shorter-acting (say 2.5h very intense trip I prefer much more than 6h of less intensity). A profound, maybe a bit life-changing experience. Laying down, eyes closed, listening to some mellow shamanic music, I went far and beyond anything I can explain with my words, dissolving senses, myself, and putting it back again afterwards piece by piece.
It was pure goodness and positivity, but I can imagine if it was so strong but negative it could have been soul-crushing. Pair it with already fragile personality and the need for professional oversight is always a good idea IMHO. Educate on top. Ignore on your own risk.
I suspect there’s a lot of self selection at work already. The vast majority of people don’t jump straight into psilocybin and LSD, they progress to them by taking softer drugs like alcohol and cannabis. I think a lot of people who don’t need “adjustment” figure out drugs don’t do much for them and stop before they take the intense psychedelics, or they figure it out at lower doses and stop before they take the intense dose.
Are you saying the claim that psychedelics are effective treatment for depression, PTSD, addiction etc. are simply because those who try it suffer those conditions? What about the part where they say it works effectively? Because I don't think alcohol or cannabis are claimed to be an effective treatment for these conditions in the same way that psychedelics are. The idea that it works seems irrelevant to your conclusion.
sounds like a reasonable hypothesis, that people who are unhappy with their emotional/mental state might be more attracted to altering it, or might experience results they consider more positive.
how do our brains decide to do anything, like eat ice cream? "hey, I loved that last time". We know that drugs are not experienced as universally positive because many people who try them in college do not go on use them throughout their adult lives.
But the part you miss is that it works. This is anecdotal for now but people are looking at evaluating that more objectively.
It's not even a stretch if you squint at this. The currently accepted treatment is SSRIs, the second S standing for serotonin. Psychedelics work on serotonin receptors. Why would it be surprising that if you tweak your serotonin receptors, you get treatment for depression? Again, this is not true of alcohol or cannabis.
No that’s not what I’m saying.
Ok. Then I misread.
everyone considers that, but because they’ll be dead by the time the studies narrow down anything they chose the substance that moves them towards results - or doesn’t
everyone can perceive that psychedelic is doing many highly variable things at once and probably shouldn't be recommended, so they just say their experience
the vast majority of people who try psychedelics are not trying to escape untreatable clinical depression, they are doing it recreationally, for a roller coaster ride which they believe connects them with the Almighty or the Unknowable or the Dao or the All-loving Everpresent or the "insert word that sounds profound" <-- oh, the Profundity!
These people are inspired—perhaps by the Almighty, i'm not judging—to preach The Gospel of psychedelics and praise any confirmation of these miracles. I'm simply pointing out that what appears to be the Omnipotence of the Almighty might very well be Selling Your Soul to the Devil for all you know. I'm an atheist, simply using metaphor to get the point across to you.
When you talk about how powerful medication is in warping the brain to cure intractable mental problems, that is not at all an endorsement of recreational use. Heroin makes you feel like your mother not only loves you, but makes up for her not loving when she abandoned you as a baby. Is heroin therefore a good idea? (and if you say "that's chemical dependency", you completely miss the point)
Idk how many people trying psychedelics for the first time are that interested in the shamanic gods or whatever as much as they want life altered in a fun weird way. In college when people did LSD or mushrooms, they were usually most interested in the visuals.
what point do you think needed to get across to me? did you think you were replying to someone else? my response was sufficiently broad to factor in non-positive and negative experiences and had nothing to do with the hyperbolic praise of some psychedelic users and that community
turns out I don't write my comments just for you. what did you write that you think so clearly showed you understood what I originally said that I wouldn't think other people suffered the same misapprehensions?
I have tried and use those things (mushrooms, LSD, MDMA) just for fun and I think they are alright if you understand that it is just that: a fun experience, like alcohol or cannabis can be. But I agree that there is a large amount of people taking those things and coming up with large amount of bullshit to justify taking it, in an attempt at pretending that they are more than just fun. It's always people who are very status conscious, hipster like, with narcissistic tendencies who want to impose their viewpoint in a way that makes them feel superior.
As far as I'm concerned, I think those things should be legal because not only sourcing them is easy anyway but it also escapes all quality control and regulation even though we still agree to sell much worse things as a society (like tobacco) and that's very incoherent.
I don't think any of the new age bullshit theory about healing mental illness (an already loosely defined thing) or whatever else is correct, but what is probably true, is that most of the stuff sold by the pharmaceutical companies is not any better (when it's not much worse) yet it is legal.
This is a classic case of capitalism bullshit: if you are having fun, you can't be a productive individual so that's not right, but in the meantime please buy our very similar drugs that's supposedly have the same results, without the fun.
One reason the advocates are going overboard with all the claims is probably because the industry is allowed to do the same with much less scrutiny, so it is an attempt at equilibrium, I guess. I doubt they will be successful at fighting fire with fire but it is annoying that it is such a political issue, people should be allowed to take those things if they want to...
although I criticize the same people, I think your viewpoint is too dismissive
without prior knowledge of what psychonauts say, I also experienced increased empathy or ability to relate to more people and animals. body language, cues, things that maybe come with mental development or maturity but seemed more refined and accelerated. on the empathy and EQ, it seems to wear off. so noticing that is a shared experience is fascinating to me, I wish it could be controlled for specifically to refine that aspect of the substance or trigger in our minds instead of jumping into the debate about legalizing that specific substance, and I understand the limitations in testing it, both from a legal and regulatory standpoint and from a control group and study standpoint
this leaves us at square one, where I can appreciate others experiencing it but I cant quite recommend either due to how varied the experience is
Same. I came to them as an older person (late 40s) who basically had only tried pot a few times prior, and nothing at all before late thirties. I don't drink.
My few experiences, the first few times, over the course of a year, spread apart by 3-4 months, went from extremely dark to .. just positive, except the last one, where I had no visuals, no bliss at all, and just came to terms with something else in our lives that was going wrong.
The dark ones were rage and anger, and now it seems just gone, like there's nothing there. Like a weight lifted, and seemingly long term.
I'm want to try them. I figure growing them myself is the safest way to go. Got 10 bags of Uncle Ben's brown rice growing mycelium right now.
If you are in the sf bay area, you can just go get what seems to be a variety of high quality, and some tested and stamped (Netherlands) mushroom products at Church of the Zide Door
Can you share some info on how much you took, and in what setting you took them, what you did on the trip, etc? I have a bunch of shrooms sitting in my cabinet but I havent had got any life altering effect out of them.
Same: I saw crazy stuff, but when the effects wore off, nothing had changed.
Yes, that's pretty normal, that's actually expected behavior. I think people saying it changed stuff are the ones having a problem in the first place (reality perception, lack of sensitivity or whatever).
Just like alcohol, those things are basically a poison, that you do not die from, provided you don't overdose (you probably have more chance dying of alcohol than mushrooms but still...).
People should take them to have a bit of fun, just like getting inebriated with alcohol and moving on with their life.
Beware of people who tries to pretend more, that are most likely full of shit and you can probably ignore most things they say if they lie about that...
This would actually be my preferred trip. I just want to have fun, its been so long since I had genuine good fun. Im tired of all the mental reflection.
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
I did 3 sessions of 8 grams in silent darkness for 3 weekends in a row and that basically "beat the devil out of me" as they say - it was very very difficult, and a lot of work, but well worth it.I've only felt the "brain haze" (I call it) once since then, I took a gram and went for a long walk in the forest, back to no haze. It's been about 7/8 months and I can feel the "haze" building in my mind again, so I plan to do another 1g in the forest sometime in the coming weeks.
However, my personal experience has been that Psilocybin != Psilocybin - the mushroom itself is super important to the process, much like Indica and Sativa have different ways of connecting you to the mind and the aether, Psilocybin (at least for me) VERY much is the same thing, and it's much starker than cannabis is. Getting into woo-woo land here so apologize: I have some concern that just "Psilocybin" isn't a good prescription, that the "spirit" that works on you is unique to the mushroom family, and that both not knowing the mushroom to prescribe and also being clinical about it (Psilocybin vs Mushroom) may not be a good direction to go in to help people with their issues. I also think that about LSD, it might work a bit for a while, but imo it's not the best tool.
Totally agree. The variance between species can be dramatic! 2.5 grams of Golden teacher was a standard trip, vs 0.5 grams of PES Amazonian was enough to send my friend into a full blown “awakening” (physical responses and everything).
It’s fascinating how they can hit different.
Also important to keep in mind the same dose can hit someone different each time depending on surrounding life conditions. I’m a big believer that the mushrooms “show you what you need to see” at any given moment, and that can sometimes range considerably.
> The variance between species can be dramatic! 2.5 grams of Golden teacher was a standard trip, vs 0.5 grams of PES Amazonian was enough to send my friend into a full blown “awakening” (physical responses and everything).
Hallucinogenic experiences are rarely the same. So you can use the same amount of the same batch 3 different times and have 3 totally different experiences.
Some people claim that you can control experiences by contolling "set and setting." I don't buy even that; all we can really say is that the experiences are not consistent between trips and we don't know why.
It's really hard to say because your mental state of being, how tired/hungry/etc you are, and thr environment you take it in are huge factors.
Taking it alone vs with friends is going to be a dramatic difference on its own, just because of what neural pathways are active when you take them.
Anecdotal case study involving a community of about a hundred enthusiasts: many in this community held the opinion you do, which is that something about the mushrooms themselves is unique to the psilocin experience (psilocybin is not always present, and in any case, metabolizes to psilocin).
Then 4-actyl DMT, sometimes call psilacetin, became broadly available. This is a synthetic pro-drug for psilocin, just as psilocybin is a naturally-occurring pro-drug for psilocin.
After that, the opinion that the mushroom per se had anything to do with the experience became very rare. It turns out that psilocin is meaningfully different from, in particular, LSD, 2C-B, and MD(M)A.
There's definitely something special about it. But that something is also present when it comes in vitro, not just in vivo.
I'm of the opinion that psychedelics can fulfill a similar role to religious catharsis for the maintenance of mental health.
8 grams in one sitting? Im not even so worried about the psychological response but even a gram can give me extreme stomach pain and nausea that ruins the whole thing.
LSD has somewhat the same effect but in a cleaner way. It's not really about the mushroom itself or the way you ingest it.
That being said, mushrooms are not very good regardless so you can process them in a way that makes it palatable (teas, blended smoothies, etc). But that won't make that weird nausea feeling disappear, you just get used to it and it slowly becomes unnoticeable as you progress on the "experiment".
The nausea is a response of your body, telling you that you ingested something bad, because that basically what those things are: a poison, just a non-lethal one, and we know the positive fun effects so it makes it worth it, otherwise you would just want to throw up !
I havent had the same effect from LSD, I also didnt have it the first few times I took it weirdly enough. I think how anxious you are seems to determine how much attention you give to the stomach pain.
Last time I was sitting there miserable for an hour and I started thinking this is life in general. I can either continue to cry about the bad or try and fill my time with something positive. I started to take a walk and think more positively and it seemed to do the trick, for a bit anyway
8g dried, overnight in lemon juice in the fridge then in the blender, chug a small glass of some type of smoothie from the store, chug the mix, chug a bit more smoothie, get into bed totally naked, wait. I did a looot of research and talked to a lot of people who have been down this trip and decided just to remove the variance of middle dose land and just put myself in "not aware" set. It worked well for me, ymmv.
making a tea with slightly acidic not-too-hot water helps quite a lot
also chewing fresh ginger or ginger tea
starting on an empty stomach, of course
but surprisingly, sometimes a little bit of miso soup midway can help with the "gastroparesis" type nausea that can emerge late stage
and also a little bit of diphenhydramine if it's still bad (like less than an antihistamine dose)
even if it is all kind of lipstick on a pig :)
My friend once described to me how mushrooms differ from alcolhol: With mushroom you get the hangover first and then the high. With alcohol it is the opposite.
the taste is really horrible and the lemon doesn't go well with it
^^^ much like the terpenes in weed different mushrooms have different chemical compositions that alter the way your body interprets the psilocybin. Cubensis make me laugh/most folks I know get the giggles on them. Blue meanies make you see things (super visual). Or atleast this has been mine and others experience over eh, probably around 20 to 30 trips over the years.
Lsd is good but definitely not as good or as easy on the brain as mushrooms. Dmt is wild, dmt with a maoi I'm too scared to try.
I've tripped a lot. It's my preferred way to party, but these days I party rarely. Mdma,ket,coke,heroin,speed all leave me feeling gross and the risk factors for addiction are far too high for my liking.
Psilocybin tolerance starts building immediately. Even if you microdose (100 mg), it will stop being effective after 3-4 days.
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.
100mg psilocybin is several times a heroic dose, but 100ug is far below a microdose. Do you mean 100mg of dried mushrooms?
I think he means 100mg of mushroom body, which might be 1-2mg of psilocybin.
Is there evidence of this?
Psilocybin has always made me not want to drink for extended periods of time after use. Always saw that as a great benefit.
SSRIs did the same for me.
That sounds great. How can I try it?
That is so wonderful to hear!
Same. Grew them myself. Microdose regularly. Take big trips once in a while. It completely changed my life.
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.
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"
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.
There are plenty of medical substances out there that are chemically similar to recreation drugs. Particularly in the fields of painkillers and anaesthesia.
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
Unfortunately it's hardly possible to do proper case control studies with psilocybin, since the psychedelic effects cause unblinding.
This is a problem with SSRIs as well; studies have found most people can correctly guess if they’re in the study group or control group.
A true double blind study would require a drug that has similar side effects via an unrelated mechanism, but nobody has attempted that as far as I’m aware.
There was this interesting one though where they deceived patients into believing they were taking an “active placebo” instead of an SSRI, and found that the benefits went away, which is very interesting and raises a lot of questions about the true efficacy of these medications: https://www.nature.com/articles/s41398-021-01682-3.pdf
If there is a medical question that double-blind studies cannot answer, that doesn't mean the question is unanswerable. It means we should be more skeptical of non-blinded studies (or worse studies that pretend to be blind), and we should look for alternative ways to address biases.
You could compare against other psychedelics. I’d be interested in that.
You could also test it on severely sleep-deprived experimenters undergoing sensory isolation, but that would never get IRB approval.
Sleep deprivation is thought to temporarily relieve depression in a lot of people, so it wouldn't really be a placebo anyway.
https://www.pennmedicine.org/news/news-releases/2017/septemb...
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.
There are many hints at psilocybin not being different to LSD, some researchers opted for psilocybin for trials just because it was less known to the wide audience and had less cultural baggage than LSD. There are some comparisons, e.g. https://www.nature.com/articles/s41386-023-01607-2
Hardly an issue. When people do similar studies measuring say the effects of prescribed exercise vs not they are also unblinded but we still get good data.
I've never found it compelling that blinding isn't possible for drug-naive patients. There are other drugs that could induce a "trip" and an unfamiliar individual could mistake for a minor psychedelic experience.
Really? name one.
Dissociatives would work, like dextromethorphan or ketamine. Psychedelics are a subset of hallucinogens.
When you don't know what a psychedelic experience is, any mind altering substance could do. For someone who never got drunk, it could even include alcohol.
It is very hard to describe in words what a psychedelic experience is, so without a reference point, it is hard to tell if what you experienced is one or not.
Is alcohol the best you could do? I have a feeling that alcohol can definitely help with depression Probably one of the oldest drugs used in that regard
of course there aren’t actually that many drugs.. you clearly couldn’t give another tryptamine they are kindof all the same. I guess you could give a phenethylamine but obviously those are probably good at treating depression too so your studies gone to shit I suppose you could give a deliriant but that just sounds mean.
Ok but now you're not comparing drug vs no drug but drug vs other drug. Yes it can be blind, but it's a cometely different study now
Suggestion alone can make you feel high. I remember someone telling me that he got high just by touching sweaty people in a music festival where most people were high, clearly, that's placebo. And that guy was far from drug-naive.
And they sometimes give active substances to the control arm to have an effect. I remember in a covid vaccine trial, they gave the meningitis vaccine to the control group to mimic the side effects of the covid vaccine they tried. Here, they actually gave a microdose of psilocybin (1mg) to the SSRI arm. I don't know why, but maybe it was enough for them to feel something without having the full effect.
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.
> we do not know, really, what goes on in there when you take a drug like Psilocybin
FYI, same goes for SSRIs. The scientific consensus is that the serotonin deficiency theory of depression was wrong. When SSRIs actually work, we still don’t know why.
I’ve had bad trips, too. Very bad, but I still think that psilocybin (in a controlled, supportive setting) is a better bet. My bad trips were all due to being in bad settings and being completely unprepared for what could go wrong. I was young and dumb and just fucking around. But tripping in positive supportive settings was incredibly helpful. And if we do find a way to do this right, then people don’t have to take drugs for the rest of their lives. Psychiatric drugs are generally lifelong sentences, and negative side effects tend to compound over time, which often leads to polypharmacy, and more side effects.
I agree. But I don’t think psychedelics are the end all be all, that’s all
SSRIs barely work. For mild to moderate depression a placebo works similarly or better. Only for severe cases of depression are SSRIs found to be helpful because they surpress all emotion.
~50% response rate for people with major depressive disorder isn't "barely working" -- for millions of people, SSRIs significantly improve their quality of life. Unfortunately, there is no "one size fits all" solution and often those of us with MDD have to try different medications, in conjunction with a (good) therapist before we find what works best.
Personally, I've run the gamut on SSRIs and they never suppressed all emotion.
Maybe the effect is different when prescribed for something other than depression, but I did not find my SSRI to suppress my emotions. It simply helps me curb rumination and negative thought spirals. Helps to feel "lighter" and simultaneously more grounded. If anything, that allows me to feel _more_ positive emotion rather than suppressing it.
Cool, glad you had a positive experience. My experience was the opposite: emotionally numb to the point where awfully bad things happened in my presence and I barely shrugged.
Being unable to feel joy or pain, being unable to cry when a loved on passed on; these were the hallmarks of my time on SSRIs. Never again will I subject myself to these drugs.
It took me twice as long to get off them as I was on them. Two years of prescribed meds, 4 years to get off them. Six years of my life spent as a literal zombie person.
We don’t know why they work or don’t. Our experiences are just anecdata.
> Our experiences are just anecdata.
Just?
Anecdotes matter
Worked great for me. Placebo might have worked too, but doctors don't prescribe those!
I was specifically thinking of this paper:
https://journals.plos.org/plosmedicine/article?id=10.1371/jo...
As well as the experience of many people close to me that used SSRIs.
This is blatantly false. I've been on a few. Some didn't help, some made me worse. The one I'm on now is extremely helpful, and saved me.
None of them had any suppressant effects on my emotions at all.
[dead]
For folks that are interested in anecdotes about psychedelics, I recommend reading Erowid expertise vaults as what gets volunteered here is very narrow and not representative of the population as a whole.
I would know, as my psychedelic mega dose stories are very different from this and also completely unique to me.
I’ve done 500ug of LSD and it was great fun. I scheduled a day off to rest ahead of time and was back to normal after that.
250ug of LSD + 1 full ounce of golden teacher psilocybe cubensis and had a somewhat spiritual experience, took a couple days before I wanted to resume normal life.
+ a dozen or more similar stories
There is a reason why “set and setting” is repeated so heavily when instructing people on how to use these substances. Any discussion of potential subjective benefits or harms of a psychedelic in the context of an experience without specific accounting for that is fundamentally incomplete.
That being said, if my experience sounds ridiculous to you, that’s because it’s unique to me, just as others’ are unique to them. There isn’t really much to be gained by talking about individual experiences other than it’s an entertaining topic of discussion. It gets everybody exactly nowhere closer to establishing the objective clinical value of these things, though.
You shouldn't compare mega doses for shrooms vs acid, they both hit very differently
shrooms feel kind of weak until you get to mega dose territory
I wouldn't recommend a shroom mega dose either, it feels too chaotic to take anything away from
I very much disagree, the effects are extremely similar, to the point where if one could match the active substance dosage as well as absorption rate, you would be very hard pressed to tell the difference.
The relative difference is because people generally don't process their shrooms very well and they take much longer to digest (slower release over time) and also its very impossible to judge the potency of the shrooms beforehand (so most go on the safe side dosage); as a starter shrooms are more unpredictable than truffles.
I had the same argument with a friend who gave me a bit of LSD (total dosage unknown, it was edible) and I tried a few days ago, it was basically the same as good shrooms. In fact, I believe the dose was on the low side, it was faster to take action but the "core" experience was shorter and "lower" than just 15 grams of good truffles.
The only thing with LSD is that it takes longer to completely clear out of your system (because it is already extracted in pure form, while shrooms have to be digested/processed by your system in a less efficient/effective way) but I don't like that very much because you end up in this in-between state where you are clearly not high anymore but also restless with secondary effects that are not really cool/interesting.
In any case it would be rather surprising if it was different, because molecularly they are extremely close.
None of this is true, for various reasons. Psilocybin and LSD are qualitatively different above very low doses. They have a lot in common, but only a person that is basically unfamiliar with one or both would call them identical. The experiences become more distinct the higher the dose.
Psilocybin/psilocin has different binding affinities than LSD, is metabolized differently etc. They are, quite simply, different drugs.
>The only thing with LSD is that it takes longer to completely clear out of your system (because it is already extracted in pure form, while shrooms have to be digested/processed by your system in a less efficient/effective way
This is borderline gibberish. The “purity” of the “extraction” (???) has nothing to do with metabolism, protein binding or excretion. The LSD expense typically lasts longer because… it is a different drug. Your body treats it differently than psilocybin because it is different from psilocybin.
And the molecules do not look that much alike, unless you think that all indoles look alike. Even if they did, molecules that look alike do not necessarily act alike (eg H2O and H2O2)
Psilocybin:
https://en.m.wikipedia.org/wiki/Psilocybin#/media/File%253AP...
LSD:
https://en.m.wikipedia.org/wiki/LSD#/media/File%3ALSD_Struct...
'great fun' seems like a weird way to describe a 500ug trip. Did you have some tolerance before this, and do you have very high confidence that the dosage is accurate?
No tolerance, and yes the dosage was accurate.
I picked “great fun” as a description as a shorthand because, while I could write more about it, it had little to no net positive or negative impacts on my mental health. For the purposes of this discussion, “Great fun” is kind of meant to communicate that the story is neither a warning or a recommendation regarding depression or any other mental health condition.
500µg is an immense dose, unless you have tolerance. Tabs usually have much less than the claimed amount. What was the source and form that makes you think 500µg is accurate? When it's 250µg or more, it's so overwhelming that many people don't have recollections from the trip after some point.
I didn’t write an extended trip report of a massive dose of LSD because this isn’t erowid and the details of the trip itself aren’t relevant. I brought it up as an example to contrast the post I responded to, as my experience was different regarding long-term effects
I was very aware of and confident about the dosage and I had not had any psychedelics for months previous, so tolerance was impossible (also no medication or other drugs etc)
I believe there is a point after which the higher dosage doesn't change much, but the duration of the trip. I have noticed the same effect with mushrooms (truffles) where basically doubling the dose didn't do much. I'm not even sure it lasted that much longer, because of course you don't take them in a fixed reproducible setting where you could correctly compare stuff.
I think there is a lot of bullshit around those substances, pushed by shamanic type of people who just invent and repeat nonsense to appear unique/interesting.
The "reports" on Erowid, while interesting in a way, are also so full of nonsense that it's largely irrelevant as a source...
I was just pointing out (mostly to other users who read this) that the alleged dose is immense and would be overwhelming for most people. Wasn't questioning your experience, only asking out of curiosity about the kind of source and form that makes you confident about the dose.
> source and form that makes you confident about the dose
Volumetric dosing from a vial of known quantity.
I did various journeys - initially alone, then with an experience guide. Mostly to explore a childhood trauma - mild, but traumatic enough to leave me with a stutter.
There were indeed some "bad" trips, although I really do not like the term "bad". IMHO there is no bad journey, it is stuff that needs that wants to be seen.
Nor is the journey itself what counts, one cannot expect a quick fix from a 4 or 5 hour journey. What really counts is the preparation (4 to 8 weeks) before, and integration afterwards (again 4 to 8 weeks). In my case I also paired it with years of therapy and meditation.
It takes a lot of courage, especially to continue after an unpleasant experience (fear, grief and loneliness in my case). In my case I kept coming back and allowed myself more and more to let the bad experiences happen. Finally I just learned to be with what is, and accept things and myself the way it all is. With that came a measure of peace and insights I had not experienced before. Along with visions about the structure of existence.
But I'll stress again, just popping a mushroom won't get you there :)
Did you take it in a controlled environment like the study suggests? Every time serious conversation of medical progress comes up, it's polluted by naysayers with anecdata about how they took it while raving beside a live volcano.
We need to give psychedelics a fair chance, and sure after we can discount them. The article suggests at scale there is potential
In my experience (this thread, too), the conversation gets polluted by people that swear by their self-medication and call more cautious people naysayers.
How come every time we try to have a conversion, it always ends up all "point counterpoint" and "personal experience with the topic" and "differing personal experience" and "discussion of how those experiences relate to the topic"!? EVERY TIME!
Its almost as if all experience is subjective…
The only valuable conversation about such research is an objective discussion of the quality of the study at hand.
> The only valuable conversation about such research is an objective discussion of the quality of the study at hand.
No
People's lived experience is very useful
Those are called anecdotes.
Empirically, they're usually not nearly as useful as people think. People are on average unreliable observers of their own experiences.
Much better than individual anecdotes are collections of anecdotes that are searchable and somewhat categorized. A lot of old school drug forums provide this.
Much better still is systematically varying data and taking statistics to separate signal from noise.
In the pre-modern world people had a very different relationship to death and there wasn’t anything like anxiety as its experienced today. Psychedelics are essentially an attempt to bring someone back to a more “authentic” experience of life before technological controls settled in. Perhaps its better to take the chance? I think so, but I want others to recognize it as a genuine risk that is truly unpredictable and not a personal failing on the part of the user.
I wonder what you mean by saying there wasn't anything like anxiety as it's experienced today in the premodern world. The term "anxiety" comes from Latin "anxietas", and Old English had "angsumnes", both with apparently similar meanings, so it seems the idea has been around for a while, and most likely because it's a basic human emotional condition that could occur in various circumstances throughout history and prehistory.
As for a relationship to death, it's difficult to generalise over all people throughout history, but for example in medieval Europe where you had a seemingly quite vivid belief in the possibility of hell after life, that could result in some extreme anxiety of the most inescapable kind. Maybe that accounts for some of the more extreme behaviours of those times, who knows.
> and there wasn’t anything like anxiety as its experienced today
You know that how exactly? We really do not have even remotely enough data to be able to make such boldly absurd claims.
Why did you take a very high dose?
As someone who was experienced with psilocybin some 20+ years ago, I always took fairly consistent doses (roughly 3 grams), as I could sense taking much more would be playing with fire. This was pretty much a given amongst my circle of a dozen friends who experienced these trips with me… hero doses were almost never a good or healthy idea. Fun to read about on Erowid though, mostly as cautionary tales.
My time with the substance ended after two bad trips (after a few dozen great ones over a period of 5 years), but neither produced any sort of even minor lasting effect.
> Why did you take a very high dose?
Hindsight is 20/20 but often it’s not clear at the time if it’s a bad idea or how bad it can be. I think it’s not such a fair question to someone struggling to find effective treatment for mental health issues to make a mistake on dosing. Especially given both government and medical field have historically not amenable to openly communicating harm reduction or safe guidelines for experimentation with this particular medicine.
Anyone who has ever tried to fine-tune medication for psychological issues knows how challenging it can be to get the dosages and combinations just right. In my experience, even medications within the same class can have different effects on different people, especially when combined with drugs from other classes.
The interactions between medications, as well as the patient’s individual response, are hard to predict. These reactions can change over time, too, as bodies and brains adapt, and lifestyles shift.
Yet, you often hear oversimplified statements like "depression means you have too little serotonin," "feeling sluggish means you lack noradrenaline," or "difficulty focusing means you have too little dopamine." These explanations are so reductive that they barely make sense.
The more I read about drug trials, the more I realize how little I — and even many professionals — truly understand about how these medications work and the best way to make informed treatment decisions.
> Ok like most of you I’ve taken psychedelic drugs.
I would like to see some actual data because my assumption has always been that most people have never tried any. I personally have not had any. I have always subscribed to the slippery slope theory of vice.
I literally take psychedelics once every few months to keep myself healthy and avoiding the dopamine chasing that I otherwise slip into over time. Shockingly not all drugs are the same, or even that similar and the propaganda about drug use escalation is, I'm sorry, silly.
Most people in this thread who are taking the position I’m critiquing, then
> I have always subscribed to the slippery slope theory of vice
Me too
Come on over the skiing is great!
>Thoughts came out of nowhere, I had no control over them; often the constant, unceasing flow of thought was distressing and uncomfortable.
I want to touch on this. "You" never have any control of your thoughts, because "you" isn't really a thing. Psychedelics and meditation teach us this if you pay close attention. The thoughts arise from nowhere and we - the imagined, but illusory - self are mere observers along for the ride that is consciousness.
I can imagine that using a substance such a psilocybin could cause your thought patterns to have both short and long term changes in quality (in terms of substance, not of superior gradation), however. It's also possible that your experience led to your paying greater attention to the thoughts that did arise, and over time the feedback loop of consciousness along with taking better care of yourself led to greater moderation of their genesis.
"You" can learn to steer your mind by choosing which of these thoughts to capture and dwell on, by monitoring them.
There is voluminous writing in the area of monastic spiritually about this. On the one hand, they affirm that these thoughts aren't chosen, using the vocabulary of sinful thoughts introduced by demons. But it's also clear that change is possible through prayer/meditation (not exactly identical to modern ideas about mindfulness).
I tend to agree that change is possible and you can learn to steer, but that too is no choice.
I believe that our minds are much like Large Language Models. Our brains put together and combine and mix up sentences that on average have some benefit to us. We speculate to explore possible outcomes. We practice saying sentences within our heads and then explore their possible consequencees.
It is a random (but not totally random of course) process where one thought gives rise to new ones. I think that depression means being in an indirect loop of negative thoughts which amplify each other. Phychedelics might be a way to break out of such loops. But, I'm just speculating here of course.
> Ok like most of you I’ve taken psychedelic drugs. I’ve had bad experiences sure, but I’m fine now.
I guess people with really bad experiences don’t talk about them as readily as the lucky ones. I don’t know the scale, but there must be some selection bias at work here.
I'm a little ambivalent about this response. It sounds like you're describing invasive thoughts of some kind, though your description is vague. At any rate, despite the perceived negative effects, by your own account, it apparently spurred you to lead a healthier life; in other contexts, this is precisely the thing that is praised when it comes to psilocybin.
> it apparently spurred you to lead a healthier life
No, I stopped mostly after I’d recovered. And I definitely wasn’t “healthier” then, just addled.
Had a very similar experience. Took ~2y to fully go away.
This is a real risk I see overlooked and minimized often. People should not assume it can't happen to them.
I had a profoundly difficult trip that affected me deeply. It felt eternal, and when I emerged, I could feel it in my head like some antimemetic parasite that fed off disgust and terror. I can still remember the feeling, twenty years later, if I try, so I don't. I had to learn how not to be influenced by it, and in doing so, learned about myself. And as I changed, because I was aware of what I knew, I knew when I'd changed.
Our selves are not immutable, steady states. Our experiences shape us. It's a lesson learned to guard that carefully and jealously.
funny, I could have written the same post but about boring old general anesthesia given before surgery
How long ago?
Every general anesthesia I've had was basically "OK you'll start to get sleepy now" and then "ok we're finished" and zero awareness of any elapsed time.
The paper here is worth a look: https://news.ycombinator.com/item?id=36323275
Also this post has stuck with me through the years: https://news.ycombinator.com/item?id=24566568
Be sure to scroll down to the comment thread started by myself248.
Yeah, maybe don't take "very high doses". I've not done that. And not had any seriously bad experiences. Maybe like everything else is all about moderation?
It was 500ug of LSD mixed with probably 6 or 7 drinks of alcohol. Suffered serotonin syndrome for a few days afterwards.
Regardless I’ve heard stories of people having severe long term psychological issues from even relatively light doses, simply because of how their body in particular interacted with the drug.
That’s a massive dose and you mixed it with alcohol. That is in no way a responsible way to try out psychedelics. You are right that everyone reacts differently which is why you don’t take a very large dose mixed with other drugs.
Anecdotally, ayuasca quite literally saved my life and helped me tremendously when I was spiraling into a deep depression. Psychedelics when taken responsibly in a controlled environment under supervision can help a lot of people.
500ug of LSD isn’t really a standard dose. It’s almost double your typical dose.
250ug of good acid is still a very high dose! 500ug is more like triple of a typical sane dose. milage may vary i guess but 300ug sent me out of this world
According to Erowid, a "light" dose is 25ug-75ug, a "standard" dose is 50ug-150ug, and a "heavy" dose is 400ug+.
I know a guy who took 1000ug. He told me he had side effects / visual glitches for about an entire week
It's such a bad idea to combine alcohol with psychedelics. You should lead off with exactly what you took so as not to mislead others.
As I said my experience incurred more risk of severe long term side effects, but those are possible in any circumstance with any psychedelic with even a single, low dose.
Thank you for telling the story.
To me, it’s interesting to consider the inflammatory aspects – the immunomodulatory effects of LSD and other psychedelics on one hand and alcohol on the other.
It’s well established but little-known that psychedelics have a very significant inflammation-reducing effect which includes drastic reduction of neuroinflammation. (I’m fairly sure that this is a primary reason why they work for depression and anxiety; There’s basically always elevated inflammatory biomarkers with these disorders. Stress is directly causative of neuroimflammation.)
Here’s a really solid review paper from 2017 – today a lot more knowledge has been accumulated: https://www.frontiersin.org/journals/immunology/articles/10....
Alcohol is known to be pro-inflammatory.
I have a hunch that these two disjoint forces on the same physiological systems can have made things worse.
You got serotonin syndrome from LSD?
That is incredibly rare, so rare I can’t find any other documented cases
Edit: did you test it to make sure it was real LSD?
I'm somewhat surprised there's only one comment here asking this.
Yes, it was definitley real. I mixed it with alcohol that’s why.
Did you test it?
> Suffered serotonin syndrome for a few days afterwards.
What sort of physician diagnosed you with Serotonin Syndrome? What symptoms did you describe to them, and what criteria/evidence did they use to arrive there? Were they able to use differential diagnosis to rule out other conditions?
Did you return to the same physician after the symptoms ceased?
Not OP, but the answer is probably what you expected. That being said, as someone prescribed multiple serotenergic drugs concurrently who was knocked on their ass by an errant Vit D dose, the symptoms are pretty obvious (and terrible) and do a good job of convincing one to “not do THAT again”.
I know, right? This is why we must be extra cautious with anyone's claim of disorder or disease, because just because someone thinks they are ill with a particular thing, doesn't mean that they, or even their HCPs have done due diligence -- modern health care is nothing like House or Doc Martin.
In fact, Wikipedia's fatal flaw is that we're forced to take medical claims at face-value when they're made by the subject himself.
Personally, my HCPs are very conservative and reluctant to diagnose -- particularly something they can't treat, and especially adverse, untreatable side effects such as "gynecomastia" or "tardive dyskinesia", etc. (Those could contribute to material grounds for lawsuits!) What physician in their right mind would formally diagnose "Serotonin Syndrome", other than one who's on the payroll of a tort/malpractice attorney?
It's interesting for me to balance a distinct tendency for Somatic Symptom Disorder (also shall never be formally diagnosed) with an impulse for self-knowledge, but an aversion to shitty "treatments" that invariably do more harm than good.
500ug is nuts
[flagged]
>You ain't right in the head to begin with, my friend. Oh wait, that IS your defining problem.
That is WAY out of line.
Yeah, up yours too.
I was trying to see how far I could go
Well it's generally recommended to "go far" cautiously in several steps otherwise you can severely damage yourself.
Anyhow I expect you to be fairly young so that explains it somewhat. If you're 50 though then it's double weird :)
Very high doses used to be my jam. I have no real way to tell what the actual dosages were with LSD, but anywhere from 5-10 blotters was pretty typical for me, and had many positive experiences this way. Conversely, my 2 worst experiences were 2 tabs and 1.5, with the second being one of my least fond memories from my life.
I wrote out a lot more detail for this comment, but pruned to just attempt to make these points 1) generalization here is (generally) not very helpful and also 2) I've come to believe "set, setting, & dosage" are typically listed in that order because that is the order of importance.
“Like most of you”
“Objection, assuming facts not in evidence”
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.
Conversely, for some people trying to fix depression with therapy and guided meditation can be a bit like trying to fix a Swiss watch with therapy and guided meditation. Everybody is different!
This isn't some erowid report. This is actually about studies being made by professional researchers who are publishing their results.
Evidence based medicine is always better than layman opinions like 'psychedelics are a mental sledgehammer'.
I agree, that taking psychedelics is likely not a good idea. But the analogue gives in my opinion totally wrong picture of the actual risks. Psychedelics, at least psilocybin, are quite harmless compared to almost any other substances. The reason for that is that they aren't very habit forming.
Personally I used psilocybin recreationally back in the days. Got once bad experience and ended up in a psychosis and to hospital. I got better in couple of days and long term effects were nonexistent.
Then I have couple of friends whose basic substances are just legal alcohol and cigarettes, and boy have they fucked their lives with those. It just takes a long time to do it that but psilocybin for sure does not lead to that kind of path.
There is actually a ton of incredibly fascinating knowledge about what psychedelics do – neuroimmunobiologically the effects are profoundly interesting. It’s a surprisingly sharp and specific instrument, certainly double-edged though.
https://www.frontiersin.org/journals/immunology/articles/10....
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.
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.)
Thank you for the balanced opinion. It's a rarity here.
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.
How do you even go about proper dosing and frequency of psilocybin use? Just random guess?
Anecdotal but whenever I’ve been asked for this guidance (having been around the block, but not a shaman by any means) I ask about the person’s dreams. Do they usually remember them, how intense are they? More intense = start with lower dose (maybe .5g). Less so maybe start with 1 or 1.5g. Of course this is subjective and relative but a rule of thumb that has worked reasonably well.
For frequency, that depends on a variety of factors I suppose.
I don't plan on ever taking psilocybin- but why dreams?- Asking cause I almost never remember any- unless I wake up at a weird time- or sleep in a weird circumstance.
Is it indicative of anything?- I sleep really well, never had any issues with sleep- and wake up well-rested. Is it better to remember more dreams?- if so what are the benefits and how to go about doing it?
I’d love to have an answer to this! As I said this is anecdotal, based on many years of experiences with friends, and the ones tending to have more vivid dreams seem to have more intense trips given equivalent dosage. It became a bit of a pet theory at some point so I ask about it. I wouldn’t be surprised if there’s some confirmation bias or something like that at play, but given the kind of hallucinatory nature of dreams I can also imagine some sort of linked mechanism.
I also rarely remember dreams and despite occasional exceptions wouldn’t consider most of them vivid. So I tend toward heavier dosages :)
Note that most of the responses you're receiving, while accurate, are in terms of units of dried cubensis mushrooms, not pure psilocybin. A fresh cubensis mushroom weighs about one-tenth its original weight once it's fully dried, and when dried they usually contain about 0.7-1.0% psilocybin by weight. So 2.5 grams of dried mushrooms will contain about 25mg of psilocybin, which is the "25-mg oral dose[] of psilocybin" given in the study under discussion.
A practical approach is to take about 1.25 grams of dried cubensis, wait about an hour to see how you feel, then try another 0.5 grams if you're up for it, and then another 0.5 in half an hour. By that point you'll have ingested enough to notice effects for sure, and you'll have confidence what your personal right dose is.
Beware of tryptamine tolerance: wait 2 weeks between doses to reset your sensitivity.
Each mushroom contains a different amount of psilocybin. You can calibrate a batch by grinding them all up at once in a coffee grinder and trying a sample. (Always be careful taking powdered mushrooms that someone else has ground up, because you don't know whether anything else has been mixed in.)
Also look up "lemon tek" to prevent tummy upset.
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.
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.
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.
The 2018 Hemp Farm bill gave the balls back to the citizens that the 2013 Analag act neutered.
Seeing mushroom extracts with all the alkaloids included besides psilocybin at gas stations may be a temporary point of stability until I can go to the "21+" store in 2030 to get my preferred arylcyclohexylamine and phenylethylamine variant.
From what I understand, those “magic mushroom” edibles sold in head shops and gas stations are amanita muscaria derived, which is a completely different psychoactive substance with different alkaloids. Toxic to the liver too, in ways that a cubensis is not.
I was aware but I should know to put disclaimers in drug posts on HN at this point, as others may not be; thank you.
That being said, it did have an uncomfortable but brief 'burning/cleansing' feeling reminiscent of Lyseragmides that that most tryptamines / 4-aco-DMT / penis envy / cubensis / 5-MEO-[xxx] did not, and more visual distortions with notably less headfuckery / low body load.
I recommend a single try; the tolerance seemed to eliminate effects nearly immediately.
Northern shamans drank reindeer urine after the animals had eaten amanita muscaria. Passing through the animals reduced the toxic component but left enough alkaloid to trip balls. Maybe the gas station edibles have removed the toxin.
Personally, I trust gas station drugs as much as I trust their tuna sandwiches
signs point to no:
https://www.cbsnews.com/news/magic-mushrooms-found-in-recall...
Geneva is home to the only Swiss hospital offering psychedelic-assisted therapy. [0]
Also, Peter Gasser, a Swiss therapist acquainted with LSD during the 1988-1993 window, was granted approval to carry out the first controlled study of LSD-assisted psychotherapy in more than 40 years. [1]
[0] https://www.swissinfo.ch/eng/science/can-psychedelics-therap...
[1] https://theswisstimes.ch/lsd-and-magic-mushrooms-how-switzer...
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.
Purely out of curiosity, which drug is this, if you don't mind me asking?
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.
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.
It's already being used in therapy. Oregon is giving licenses.
https://www.oregon.gov/oha/ph/preventionwellness/pages/psilo...
In Oregon enforcement of what passes for our drug laws here is so lax (cops quiet quit long before covid) that it's de-facto legalized.
I've literally walked down Portland and had random homeless people unprompted yell out "Want to buy some shrooms?"
There have been unlicensed openly practicing shrooms businesses which survived far longer than one would expect for such a "regulated" industry.
I doubt about everywhere, as shrooms are sold in shop around here.
In the US, those aren’t from mushrooms that contain psilocybin or related neurotransmitter analogs
It definitely happens:
https://www.seattletimes.com/business/oregon-store-allegedly...
https://www.sfgate.com/cannabis/article/sf-magic-mushroom-ch...
Where is here?
Clearly not North America
california has mushroom stores
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.
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.
> "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?
> A more holistic approach to health care would be beneficial.
I've commented on this elsewhere, but with psychedelics in particular we wind up in a weird space around our normal approaches to health - for instance, there's a lot of effort right now on finding the chemical mechanisms by which psychedelics affect mood, with the goal of creating substances which have the same impact on depression without the phenomenology of the trip. My suspicion is the trip is the treatment, or at least part of it - that the experience of being in an entirely different mindstate, of reacting to the world in a fundamentally different way using different mental pathways for several hours - is a core part of the treatment. Medicine has a bad habit of ignoring the patient's lived experience - to look at the patient broadly as a mechanism, and particularly as a collection of mechanisms, and to see things like hypertension* as something to be treated with a chemical offset and not a reflection of the full factors of a person's life. My hope is that the psychedelics will help us recognize a paradigm shift here (like, in data leading to changes in practice, not just in their normal way), but I think they've still got too much of the taint of the hippie on them to really be taken seriously.
* I'm using hypertension as just an example of a particular ailment, I'm not making a statement on the treatment hypertension in particular.
> A more wholistic approach to health care would be beneficial.
Maybe. My personal experience has been that those "negative symptoms" were in fact the entire disorder. I didn't need purpose or depth. I needed to not be so sad that I couldn't function. I needed to be able to hold a coherent thought for 5 minutes without getting stuck into a negative spiral of self loathing.
I want "purpose" and "connection", but those things are what everybody on earth are looking for. The search for those things is the _stuff_ that life is made of. I needed help to get back to a place where I could pursue those things. Pursuing them is my life.
> 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.
Many people here are speaking from experience. I trust my own judgment over some knob in the FDA that is steeped in a culture of drug control.
> Many people here are speaking from experience. I trust my own judgment over some knob in the FDA that is steeped in a culture of drug control.
Let me paraphrase this:
Many people here are parroting stuff based on a sample size of 1, who lived to tell the tale. You trust your own judgement based on those people before the rigorous safety and effectiveness studies for the FDA, on a whim that the FDA approves or rejects drugs based on their... ? Culture of hating recreational drugs?
The FDA exists to tell you, a free individual, what you are allowed to put in your body. It has been a very long time since the FDA has been about safety only. It is wholly captured by business interests in food and drug industries. So yes, they, and the government culture as a whole, hate recreational drugs that they don't control in some way. No shooms for you but drugs that cause suicidal ideation are prescribed by the millions.
I am wary of people "looking out for your safety" when there is financial incentive to do otherwise.
Schedule I drugs specifically? The regulation around them is inescapably rooted in a culture of hating recreational drugs.
Notice how you downgraded your confident claim of knowledge to a tentative question.
What's going on homie?
It just seemed incredibly stupid so I wanted to make sure I understood correctly what they meant.
Ok, but you were spreading misinformation in the process.
And psychiatric drugs don’t ever make things worse? As someone who was severely injured by FDA approved, scientifically validated medications, I’d say some healthy distrust of a corporate-captured bureaucracy is warranted. Remember, OxyContin was FDA approved. Did the FDA ever launch an investigation into how they allowed that disaster to happen? No. They didn’t so much as say “whoops”.
> The risk is to make things worse.
That risk exists in many medical interventions. We need to quantify that risk and weigh it against the chances of making things better.
This is generally what the regulatory system tries to accomplish.
Right. But there was Oxycontin. So it's obviously got its flaws.
I don't want people self-medicating with psilocybin, just like I don't want people self-medicating with SSRIs.
Which is more dangerous?
Psylocybin? Easily?
You have to put effort into making an experience with psylocybin meaningful and helpful. It could go wrong very easily, especially for those who are in a difficult situation or headspace. (Speaking from experience.)
As for SSRIs? Safe, effective, with a handful of annoying side effects. Straightforward to use, low potential for misuse, requires sustained use for any intended effects. A doctor who already has familiarity with a patient's mild or moderate symptoms of anxiety or depression may very well just prescribe one if asked and if not contraindicated. Not that you should randomly start popping Prozac, but it's unlikely to hurt you if you did.
Ask your doctor, try the things that doctors currently believe are most likely to work first. If for whatever reason you choose to go beyond the current medical consensus, please stay safe and keep your doctor up to date.
Impotence and weight gain are not just "annoying" side effects. They seriously impact your life. Just putting that out there.
I'm not claiming they don't. Everyone experiences SSRIs differently and it's common to shop around until you find one whose side effects impact your life in a more tolerable way.
That's in contrast to psylocybin, which has substantially more serious potential acute side effects, ones that are more difficult to understand and treat should they occur.
I'm not saying psylocybin is unsafe or that SSRIs are always preferable. But if I'm asked to compare their safety? The choice is obvious, weight gain notwithstanding.
I'm not claiming they don't.
You were clearly implying they don’t when you downplayed all SSRI downsides as “a handful of annoying side effects”.
Weight gain kills. Suicidal ideation also kills many people when they start SSRIs. People have killed themselves because of permanent sexual dysfunction caused by SSRIs that never went away after stopping the drugs (and yes, this is a known possible adverse effect listed in the official prescribing information).
I don’t think the choice is as “obvious” as you’re making it out to be.
I wasn't aware of PSSD (I don't seem to be alone on that front).
Leaving this link for others to pick up for more information: https://annals-general-psychiatry.biomedcentral.com/articles...
I guarantee you the number of people who have died from SSRI misuse is higher than the number of people who have died from psilocybin misuse. I'm not referring to things a person may do in a given state, I'm talking about effects from the drugs themselves. I'm not aware of a single recorded person who has taken any dose of psilocybin, and died from "psilocybin overdose". While it may be uncommon, it is possible to overdose on SSRIs.
Sure, psylocybin won't kill you, but the threat of inescapable psychological distress is real. Maybe it's less likely if you aren't predisposed to psychosis, but you can't easily know for sure that you're not.
And yes, it's possible to misuse SSRIs, but taking an obviously oversize dose is still often a treatable situation. Combining them with depressants I think is a degree of misuse that is incomparable.
While fishing for that right dosage of SSRIs you have a person with new boughts of mania and suicidal tendencies where there's no clarity on how to stop the experiment due to the complexity of blood level accumulation.
If SSRIs started as illegal drugs, with i.e. people starting them dodging medical supervision, I think the system would be telling us they are insanely risky and well beyond many scheduled drugs.
bouts*?
> but the threat of inescapable psychological distress is real.
Really?
That is true of any meaningful experience
The danger with psychedelic drugs is very low
They wear off
> it is possible to overdose
I'm not sure that's a good metric though. Paracetamol is more dangerous than most highly regulated pharmaceuticals in that way.
So are you okay with people choosing their own dose of SSRIs?
A prescribing doctor will not magically know the precise amount of an SSRI a patient should be taking, or which one to take. For most patients, finding the right drug and dosage is a process. And just like with psilocybin, no one would want to take a random amount. Like with any drug, a person would want to be informed and have proper guidelines about dosage from the start.
> Psylocybin? Easily?
Err.. no?
This is from the Dutch National Institute for Public Health and the Environment: https://www.rivm.nl/bibliotheek/rapporten/340001001.pdf
Page 19 onward has the charts. What do do we find at the very low end in terms of chronic and acute toxicity? Shrooms (“paddos”) and LSD.
It always blows my mind how anti-drug people will do a handwavey gesture to the authority of institutes like the FDA, but never actually check up on what actual research says.
> As for SSRIs? Safe, effective, with a handful of annoying side effects.
Except the multitude of ways you can put yourself into a serotonin coma.
I agree with your assessment that (first) use of psychedelics should be under proper guidance. But what you refer to, “going bad”, can sometimes be a traumatic past experience that people have stuffed away and by surfacing and processing it they can move past it. It’s not always meant to be kumbaya and flowers.
Educate yourself, then talk.
I'm not saying psylocybin can't be used safely, nor have I made any claims about its relative toxicity or harm relative to other scheduled drugs. If you're arguing anything else, I don't think that report says what you think it says. As for my position, I live in SF, it's decriminalized here, I support that. So there's no need for your rude presumption that I find it generally unsafe.
I'm also unfamiliar with the dose of SSRIs that would send you into a coma, but I'm fairly certain it's shockingly large. Happy to be informed otherwise.
edit to reflect parent edit: yes, I'm aware that breakthrough experiences can be helpful. I'm also saying they should not be your first resort.
> I don't think that report says what you think it says.
The report also speaks to personal, social and populational damage.
> I'm also unfamiliar with the dose of SSRIs that would send you into a coma
Its not the SSRI itself, but rather anything that messes with your reuptake can put you into some deep problems. And of course the bog-standard grapefruit+medicine interaction.
> I'm also saying they should not be your first resort.
My point was that if we are talking drugs, yes, treatment with psilocybin should definitely be higher up the list than SSRIs. SSRIs would most likely be for life, daily. Psilocybin could be bi-annually or perhaps even as spot treatment only.
> So there's no need for your rude presumption that I find it generally unsafe.
Apologies for coming off too strong. I just feel that, reasonable as it is, the “let’s all just take a minute” attitude gives too much ammunition to conservative hoohas to stymie these alternate treatments for another few decades. Imagine if marijuana had been more accessible to people like this in the 80’s-10’s:
https://youtu.be/zNT8Zo_sfwo?si=-0xxkGE22zk9q_bC
https://youtu.be/FSdjvEnyRzk?si=urVWAeUZ4fTCdUiw
> > You have to put effort into making an experience with psylocybin meaningful and helpful. It could go wrong very easily, especially for those who are in a difficult situation or headspace. (Speaking from experience.)
> What do do we find at the very low end in terms of chronic and acute toxicity? Shrooms (“paddos”) and LSD.
Breaking your mind doesn't count as toxicity. You're not responding to the point you tried to refute.
It’s rather difficult to “break your mind” on psychedelics.
Unless you either A) already have a predisposition to something like, say, schizophrenia, or B) take stupendous amounts, you’ll be fine. And vis a vis point B, in the older days there were people who did multiple LSD hero doses, without frying their brain.
> Breaking your mind doesn't count.....
Hyperbole
toxicity is the least of _psychoactive_ drugs problems
Definitely psilocybin. For instance, if you take psilocybin and then spend some time in a cow slaughterhouse house, you might go crazy. The same wouldn’t be true of SSRIs.
With SSRIs, the dangers are long-term.
The best thing to do is to consult with a physician on matters related to your health.
I really wish we would retire this chestnut already. As if there’s a reasonable grownup option here and everything else is playing with matches.
No it’s not the best thing to do to brave huge waiting lists, call a hundred providers none of whom are taking new patients, pay a fortune out of pocket, and/or be faced with a distracted impatient person stuck to their screen who has 10 minutes for you.
And I live in Germany, not the US.
That's not clear cut. There clearly exist plenty of combinations of "situation + physician" where this is not the best thing to do. To claim otherwise may as well be religious dogma.
At the very least, consulting with one or more physicians gives more data points than you would otherwise have. If your goal is to know more, having other opinions is pretty fundamental.
Doing a rain dance and concluding that it doesn't help also gives you another data point. Praying as prescribed in 50 different religions a whole lot more data points. And so on.
I'm not a nut screaming "It's all a scam, don't participate in modern healthcare!". Just noting that it's complicated, and the idea that going to a physician is always the best option should receive more scrutiny, because it's not black and white.
I'm sorry, but how is trusting a person who dedicated 10+ years of their life studying/practicing this, and relying on rigorous safety and effectiveness research of drugs religious dogma? Are you sure you know what religion is? Are you sure you know what science is? Are you just trolling?
If you actually read the effectiveness and safety research with a critical eye, you would realize “rigorous” is often the wrong adjective, whereas “cherry picked” to the point of “fraudulent” is often more in line with reality.
Case in point: 50,000 people died, with about 5 times as many suffering life-changing serious adverse events, from “rigorous research” on the safety of Vioxx. Yes, it has since been pulled from the market, which FDA apologists often construe as “system working as designed”. No, it isn’t, even in the least, when you go into the details.
Also: Purdue and OxyContin.
Regulatory capture of the FDA is decades old at this point. Ignoring that is not a rational or healthy position.
I don't know, why don't we ask my colon? Oh, wait, we can't. I was prescribed accutane, subsequently got ulcerative colitis so bad that they had to remove the organ entirely. The surgeon said my colon was literally falling apart in his hands as he took it out. Blind deference to authority of doctors lead to this situation. They do not always make great decisions, especially if there is a financial incentive for them to do otherwise.
I'm not trolling, see my reply elsewhere.
Do you not know anyone who has spent many years of their life doing something and are still rather poor at it? You probably do. You may even have such a skill yourself - I certainly do!
that's easy to say when you forget about the state of healthcare.. everywhere, actually. I was going to say the US but in other countries it's not like you can just pop in for a chat about taking shroomies, either.
I'm not sure having a ten minute meeting with a stranger who has a PhD in internal medicine is going to yield useful strategies for curing the existential dread underpinning your depression whether you're there to discuss getting zonked on LSD or something more "traditional" like Xanax
> it's not like you can just pop in for a chat about taking shroomies
You sure can just pop in to discuss options for your crippling depression though? And sorry, I do indeed live in a country with a functioning healthcare system, not the US.
In the US normally you talk to a therapist (not a doctor) or psychologist (not a medical doctor) about your depression at length, and then if you're deemed sufficiently depressed you get a short consult with a psychiatrist (finally a doctor) to prescribe medication. This is when you would theoretically finally be able to bring up shrooms, and your psychiatrist will laugh at you, write an Rx for an SSRI, and you'll see him next year when the Rx expires
I'm not sure how it is in most countries but I'd expect the biggest difference is that it will cost you money in the US, but I've read many many horror stories about people waiting many months to have only a short chat with a physician from other countries. The lack of time available to spend taking to physicians seems to be a problem in other places too
my point is that consulting a doctor with random questions isn't a simple, casual thing people can easily do in most places. in most places you have to plan ahead and either wait a long time for an appointment, and/or there is a cost barrier.
if you have examples of countries where people are able to get to know their doctors on a personal level and can afford in time and money to talk to their physicians for more than a few minutes per year, please link them below
> You sure can just pop in to discuss options for your crippling depression though
To get a prescription for one of the the handful of drugs are are available and are considered to be effective. What else can you learn by just "popping in"?
> with a functioning healthcare system, not the US.
What do you even mean by that?
The US government severely restricts research on Schedule 1 drugs like psilocybin. Physicians don't have the data they need to inform patients.
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).
The idea that doctors aren't constantly "off base" and must be deferred to uncritically is pretty terrible.
For example, it took literally two decades after it became well known that peptic ulcers were mostly caused by bacteria for the medical community to embrace giving anti-biotics for GI pain. To this day, there are still many American doctors who don't actually know about the Nobel Prize given in 2000 for this discovery, and claim it's "stress" and tell you to go home. Some claim they "know" but than try to "change your gut PH" and still refuse to give antibiotics due to "superbug" risk.
This is a "small" thing (GI pain is not small to those who have it) - but if the doctors are screwing up such a small thing institutionally, what else do they mess up on?
One is travelers sickness. Doctors in the USA do not want to perscribe front line antibiotics for it because of fear of superbugs - but they'll uncritically go eat their lunch at a McDonalds that same day, where they consume meat bathed in antibiotic slop which is more likely to contribute to superbugs then the amoxicillin that they didn't give you would have.
Or what about right now, when it's become clear that Ozempic is literally a super-drug. Every doctor on earth should be trying to give that stuff to literally anyone.
I can go to "third world countries" with deregulated health systems and get infinitely better care that I have real control over for on the orders of 1 USD (that's how much it cost for me in Thailand to get front line antibiotics for travelers sickness INCLUDING THE DOCTORS VISIT!)
Why do we still sell Neosporin despite doctors wanting it off the market (also for risk of superbugs)? Why do few people in America use Providone-iodine for wound treatment despite it being by far the best solution scientifically for it (and it stains yellow)? Maybe it's because we're stupid. There really aren't better explanations.
What about Circumcision? I'd straight up put doctors who do it in jail and many European nations would do the same. American doctors think circumcision is just fine, and long, deeply bitter swaths of medical ethics journals are dedicated to fighting over this again and again.
Or what about the widespread disagreement over even basic stuff like digital rectal exams? There's no agreement on if they are worth it because often sticking one's hand up the butt of an old man does more damage to them than finding out that they (like everyone else at old age) have benign prostate cancer?
Doctors in America have not earned their position of deference. The scientifically minded on HN who do their own research can and often do know how to treat certain conditions better than white-coats.
Is there any evidence that psilocybin "makes things worse" or are you just concern trolling?
There are certainly reports and some research showing that developing psychosis is certainly a risk as least for some people.
Probably not…the question is, does Psilocybin have a higher incidence rate of users suffering episodes of severe depression or psychosis than, say, SSRIs. Amongst all the “spiritual” drugs, even counting THC, Psilocybin is the most well tolerated—even so, SSRIs tend to still be very safe, even if they are not very effective.
The best thing to do is to consult with a physician on this matter, еven if side effects, drug interactions and precautions are readily available and cardiac arrest and death are among them. Idk, is this worse?
What would be the point of that? I'm pretty certain that almost any physician would tell you not to consume psilocybin (especially if you are suffering from mental issues).
My suspicion has always been the majority of adverse reactions have related to improper dosing.
Anyone can have a horrible response with too high of a dose yet with self-medicating theres no sure way to know the amount of medicine you’ve ingested even if weighing.
Rigorously determining the proper effective and safe dose is part of the approval process.
Of course if it’s pharmaceutical.
People were alluding to the risks of self-medicating I was referring to that.
The article discusses the risks of treatment:
> 'He added a word of caution for therapists that "psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this."
The long-term consequences of trying to avoid such issues seem considerable, e.g. it might lead to schizophrenia if people try to wall off parts of their memories they find intolerable, though that's just speculation at this point.
> Psilocybin seems to help reconnect people with a part of themselves they only dimly remember
Is there science behind this statement?
From what I know, we understanding psychedelics work. We don’t know precisely how.
It’s a neat study. I don’t know how you account for the intense placebo effect of a psychedelic experience for six hours though. We know that traditional antidepressants may work through this method already where you feel “different” and fix yourself. Trials with an active placebo often have results very similar to antidepressants.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
I guess maybe it doesn’t even matter in the end as long as people feel better.
> 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.
> 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.
This is true of most if not all drugs / studies. That is, the drug gets "credit" for the placebo effect. Sure they took the meds, but that's correlation in at least some. That is, in some the drug did not actuay work but they still get to benefit from the placebo effect.
I rarely see this discussed. I'm not sure why (short of actual cellular test showing it was the drug that did triggered the success some of the success even in the group taking the real meds is still the placebo effect).
This might not be ethical, but given a psychedelic naive population, I wonder if the control could be given a non-serotonergic psychedelic such as salvinorin A. There would definitely be a noticeable effect, but for someone who hasn't studied the effects of psilocybin, they may not realize it. The downside is that in order to keep the duration similar, you'd probably have to administer the salvinorin using an IV drip, and a six hour salvia trip could quite possibly be too traumatic.
It might be nice to also have a non-psychedelic non-sari as well. Right now a patient could use whether they tripped or not to determine exactly which treatment they received. But if you had the full 2x2 design of {drug has trip, drug has no trip} x {drug is supposedly therapeutic, drug is non therapeutic} the existence of a trip wouldn’t reveal their exact treatment
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?
There has been a study of that on ketamine, where they used patients who needed to be put under anaesthetic for other reasons. I'll try and find it in a bit...
Edit: found it https://www.astralcodexten.com/p/does-anaesthesia-prove-keta...
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.
I think a major criticism of how this study is designed is that it is not truly "blinded". I doubt many of the participants were unsure if they received psilocybin vs escitalopram.
This is already a problem for most psychiatric drug trials; studies have found that most people can tell if they’re on an SSRI or in a control group, since the side effects are pretty noticeable.
There is evidence that this skews study results, to the point that some scientists believe that SSRIs may only be “effective” because the obvious side effects make them a good active placebo.
Being blinded isn’t some gold standard. For example we know exercise leads to good health outcomes from unblinded studies. Every study on fitness ever done is unblinded and we consider these results to be a ground truth.
"Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial" (2018)
<https://www.bmj.com/content/363/bmj.k5094>
The randomized controlled double-blind study is a gold standard. It solves for so many different biases. Without it the burden of proof is higher. Luckily, the evidence that exercise is healthy is so overwhelming that we have a scientific conciseness.
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.
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...
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.
The doses of psilocybin being used were so low as to be barely perceptible.
The participants received a 25mg dose; I can assure you that such a dose is very much perceptible.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...
Ah, I made a calculation error by an entire order of magnitude while converting that to “grams of dried mushroom”.
Yeah that dose you would notice a fair bit - it’s equivalent to about 2.5g dried cubes.
Ah, but does it beat exercise, fresh air and sunlight?
https://www.mayoclinic.org/diseases-conditions/depression/in...
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.
> There's no one to trust more than a good friend to be there for you when the ride gets bumpy, not some guy in a suit doing it for the money.
I couldn't disagree more.
Your good friend most likely doesn't have the slightest idea how to handle things if your trip goes south. Especially when they're on their own "ride". That's not to disparage anyone, but just to state the fact that there is training around these things that comes from lots of experience.
And therapists are not "some guy in a suit doing it for the money". You don't get rich doing psychotherapy -- you do it because you genuinely want to help people. And never in my life have I seen a therapist in a suit.
This isn't to say that every therapist is great or that every friend is terrible -- just that the relative success rates of being able to help someone on a bad trip, both during and after, are going to be a lot higher on the side of trained therapists. Because of the training.
>Your good friend most likely doesn't have the slightest idea how to handle things if your trip goes south.
Yes they can, everyone experienced can. It's part of having empathy.
>Especially when they're on their own "ride".
The trip sitter doesn't trip while sitting.
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.
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.
"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.
I don't think you've really considered the incentives either.
The system has as much interest in curing your depression as it does curing obesity. Long term, these conditions are very costly. It takes people out of peak condition, reduces labor pool, increases number of patients taking up resources at hospitals and doctors offices, and so on. A system which encourages these things is a failing one, as taxpayer costs would only continue to balloon.
Additionally, since the thread is about psilocybin, people would still be filling up prescriptions for those.
Also, self-medicating is also very costly. Not only to the system, as people often wind up in hospitals due to laced products or incorrect doses (see marijuana in a lot of states where dealers really aren't concerned about quality), but also to the individual. People are spending absurd amounts of money on vitamins and mushroom teas and all that in hopes it helps, but rarely is that the case due to these categories not being strictly regulated.
I think your argument is as valid as the one you're responding to.
>The system has as much interest in curing your depression as it does curing obesity.
Ironically enough, the system hasn't cured obesity (if you believe obesity is primarily caused by a poor environment) and seems to instead to be headed towards managing symptoms by hacking our hormones and brains with semaglutides, etc. But at least you can work.
If you use a similar train of thought applied to depression - we're now in a situation where something like 50 million Americans are on antidepressants or antianxiety medication. 1 in 6. This is also treating symptoms and putting people into a state of being able-bodied without being so well as to remove their dependency on the drug. But at least you can work.
So I think the original idea fits with the concerns you outline. Mass producing a few drugs to keep a majority of the population able-bodied might not be that much money in the big picture.
I'm not a firm believer in this theory, but I can totally believe an overly complex system with poor incentives and no absolute oversight can lead to these outcomes.
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.
I get the impression that there’s misalignment on what “the system” is to each commenter here. One side views it as the larger society and the other as the pharmaceutical industry.
> society and the other as the pharmaceutical industry
The market is huge and executives usually care much more about short-term (or at the most medium-term) growth. A company that actually found some magical cure for depression they would have no reason to not undercut their competitors and still make massive amounts of money even if that would destroy their target market would disappear over the next 10-20 years.
Also aren't pretty much all the most popular antidepressants and related drugs relatively very chip. Nobody is making that much money selling SSRIs. Why would pharmaceutical companies forego hundreds of billions on purpose?
I think the advertising of pharmaceutical is big loss of faith. Not to mention the opioid crisis.
If medicine was an honorable industry in the USA the might be more faith.
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...
>Post-SSRI sexual dysfunction (PSSD)[62][63] refers to a set of symptoms reported by some people who have taken SSRIs or other serotonin reuptake-inhibiting (SRI) drugs, in which sexual dysfunction symptoms persist for at least three months[64][65][66] after ceasing to take the drug. The status of PSSD as a legitimate and distinct pathology is contentious; several researchers have proposed that it should be recognized as a separate phenomenon from more common SSRI side effects.[67]
>The reported symptoms of PSSD include reduced sexual desire or arousal, erectile dysfunction in males or loss of vaginal lubrication in females, difficulty having an orgasm or loss of pleasurable sensation associated with orgasm, and a reduction or loss of sensitivity in the genitals or other erogenous zones. Additional non-sexual symptoms are also commonly described, including emotional numbing, anhedonia, depersonalization or derealization, and cognitive impairment.[64][68] The duration of PSSD symptoms appears to vary among patients, with some cases resolving in months and others in years or decades;
https://www.pssdnetwork.org/
At least, the mushroom didn't steal my mojo
Within a few hours of taking zoloft I lost all sensation in my genitals and it's stayed that way for years
I've since gotten all my hormones tested (normal), and doctors are suggesting I cycle between TRT HCG & Clomid + Dopamine Agonists
I don't have ED. My symptoms are purely genital numbness/anorgasmia/failure to finish.
I submitted a complaint to the FDA last year. I understand they're currently being sued over this.
I don't understand how SSRIs aren't classified as reproductive toxins.
Can psilocybin restore the mojo, or are you just commenting on the downside of SSRIs?
Not a cure but a treatment (sample size: 1)
https://www.reddit.com/r/pssdhealing/comments/10tjyen/a_trea...
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.
happy ending?
the little death.
[dead]
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.
Funny, psilocybin has been largely detrimental to the mental health of everyone I know.
"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.
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.
What are the more preferred plants/substances for personal growth and mental health?
If someone is unfamiliar with psychoactive drugs, I would suggest they eat a single mushroom cap in a safe, private, comfortable environment and with another person who has some experience. I think it is a more pleasurable and worthwhile experience than marijuana, which can actually be more intense and is more prone to generating anxiety and paranoia. There's lots of resources online and there are communities in a lot of cities that advocate mushroom use.
Thoughts on Mescaline/Peyote?
Mescaline is like the angry lover version of mushrooms. I did it once, two years ago to understand why it has been used, traditionally, as the baseline for comparison for psychedelic substances, and it was enlightening; it is certainly a tasting menu of the classical psychedelics, having at different points in the experience the flavor of stimulants, LSD, mushrooms and finally something all its own, but it is also much grittier and less loving than mushrooms.
Mescaline is _rough_. And honestly the "you are done with it before it is done with you" thing is 100% true, it is also very long lasting.
What would you say about ayahuasca?
Never tried it. Seems like it's vaguely hard to consume safely since it is tied to shaman woo culture overseas. Supposedly there are sessions in the bay area, but I'm not cool enough to know people who know about them, or for that matter the other things I'd like to try.
I have a plan to try it, DMT, LSD, 2-CB and 5-MeO-DMT before I'm 60, so I guess I'd better get cracking as that isn't far away for me.
I've known far fewer people who have taken it. Unlike mushrooms, I have heard stories of prolonged and difficult trips that sound much more challenging and arguably dangerous than a average-dose mushroom trip.
As someone who has personally dealt with mental health issues I attribute to use of cannabis, I agree with the underlying sentiment here.
The people in this thread saying things like, "they wear off" or dismissing clinical treatment for depression as "suits ripping people off" are delusional and embodying bad stereotypes. Just because you and your bros took mushrooms, had a few laughs and carried on "working hard on saas" or even had a beneficial, religious-type experience doesn't mean that there aren't also risks or that everyone will have a similarly beneficial experience. It's been known for decades -- both empirically and scientifically -- that psychoactive substances can surface latent or bring about psychological issues (e.g. cannabis and schizophrenia) in some people.
Now, I'm not against use of these substances medicinally or recreationally but to pretend like there is no risk and that they're a one-size-fits-all miracle cure is reckless, naive and dumb. As mushrooms and cannabis become more widely available and more powerful (in the latter case), I suspect we'll be hearing a lot more about this class of issues in the coming years.
Agreed with a caveat: SSRIs and other antidepressants are far worse.
sometimes it amplifies preexisting issues and forces you to deal with them, at least that's what they did for me
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.
my experience has been very different for everyone I know
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.
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).
Full research article:
https://www.thelancet.com/action/showPdf?pii=S2589-5370%2824...
Study design and methods:
> "All the patients provided written informed consent and after discontinuing any pre-trial antidepressants, enrollees received two oral doses of psilocybin (1 mg or 25 mg) with accompaniment from two experienced therapists for ∼6–8 h, separated by 3 weeks, as well as daily pills (escitalopram 10–20 mg or placebo capsules). Thirty patients were randomised to PT and 29 to ET."
> 'The PT condition consisted of two high-dose (25 mg) treatment sessions with the serotonergic psychedelic psilocybin, administered with support from two study therapists...and daily placebo capsules. The ET condition consisted of daily doses of the selective serotonin reuptake inhibitor (SSRI) escitalopram - 10 mg for three weeks followed by 20 mg for a further three weeks—as well as equivalent psychological support including dosing sessions with placebo-like doses of psilocybin (1 mg)."
This is an interesting way to address the placebo issue, giving a noticeable microdose of psilocybin (1 mg) versus the active dose (25 mg) for the non-control group.
Fundamentally I think psilocybin's main overall psychological effect is to push subconscious issues up into the mind's conscious processing space. Large doses can generate visual hallucinations related to those subconscious issues which can be unpleasant, even terrifying, for many people, so that's why caution is warranted. Extremely large doses cause complete dissociation from external sensory input, which is of course very dangerous for the unprepared individual in an uncontrolled situation - an experience unlikely for any herbivore to want to repeat, hence the evolutionary selection pressure for biosynthesis of such compounds by plants and fungi.
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.
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.
And it's mostly not legally acquired fentanyl that's killing people.
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.
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.
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.
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/
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
Taking LSD every few months was the best antidepressant I’ve ever tried and I’ve tried a bunch
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.
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.
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.
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.
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?
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... :)
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.
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?
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.
What you're describing sounds very much like the impact ketamine has on the default mode network (DMN), which plays a central role in your sense of self and how you process thoughts about yourself and the world. The DMN is typically overactive in conditions like depression, leading to persistent negative self-reflection or rumination.
Ketamine temporarily disrupts or disintegrates the activity of the DMN, which is likely where the sensation of "disintegration" or "ego death" comes from. This can feel like a profound loss of agency, as the very part of the brain responsible for your sense of self is being deconstructed. The disorienting part—being left with fragments of yourself—is also consistent with how the DMN breaks down, exposing subconscious thoughts or patterns you may have repressed or forgotten.
But this isn’t just a random break—it’s part of why ketamine can be so therapeutic for some people. By breaking the DMN's rigid structure, it allows for a kind of mental reset, where you can reorganize those "pieces" in new ways, often leading to the clarity or "AHA!" moments you described. The months of renewed understanding and hope after the experience fit well with ketamine's fast-acting antidepressant effects.
That said, I understand the hesitation to repeat such experience. While it can be transformative, it can also feel traumatic, precisely because it’s messing with such a fundamental part of how your brain organizes reality. We’re still in the early stages of understanding this, and while it can be deeply healing for some, it’s definitely not something to take lightly.
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/...
2022: https://www.jwatch.org/na55225/2022/08/16/antidepressants-wo...
2023: 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
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...
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.
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.
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.
> ... burnout-related depression (person worked normally their whole life but is suddenly just empty of energy and does not look forward to anything with joy) ... existential depression and anxiety that is driven by pathological self-focus (not egotism, but inability to stop focusing on one's own inner states)
Is there any rigorous operationalization of these concepts, that might be explored in further studies? Unless one can be found, these fuzzy, heavily qualitative descriptions are unlikely to be helpful for future researchers.
It's counterintuitive to me that a more specific concept/subgroup of a phenomenon would be less useful than a larger catch-all category. Is the self-rated questionnaire depression scale used in this study a good "rigorously operationalized concept"?
We are successfully treating people with this exact kind of indication/operationalization with real success already. For instance, the indication criteria for ECT basically follow the "burnout profile" I described above, with the addition of "treatment resistant to therapy and medication," and it has shown by far the best effectiveness for that kind of depression.
I completely disagree that it's not possible to operationalize the concepts above, for instance with standard BDI or MADRS, supplemented with a ratio with a cutoff to indicate a large fall in everyday functioning. Like an extremely large fall in Global Functioning Scale (GAF) localized to a distinct and pattern-breaking period in a person's life. If you think that these concepts are fuzzy and qualitative, I really hope you have even greater criticism towards this study, not to speak of concepts like anxiety, trauma, and ADHD, which are completely off the rails when it comes to diffuseness and subjectivity.
But even if you are right, that burnout-depression and existential anxiety are not possible to study because of their vagueness, it still would not make this study helpful as it's presented. Or am I mistaken? Do you think it's a good and helpful study, whose implications I should fight for in our clinic? And would I see a marked improvement in our patients, compared to SSRIs for the "Depression" group?
I am willing to admit I am wrong. The only goal is to actually help people.
Psychiatry seems to be very symptom based, depression is an umbrella term for many completely different problems that show as "big sad".
Maybe it would be more productive to base diagnosis on some kind of brain imaging.
Serenity Now, Insanity Later
But no patent, so this is "misinformation" haha
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No shit.