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.
>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.
> 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
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!
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.
> 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.
> 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.
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
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.
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
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
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.
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.
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.
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.
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.
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.
'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 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.
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.
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'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.
> 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 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.
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.
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.
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.
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.
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.
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.
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.)
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 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.
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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?
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.
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.
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.
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.
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.
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.
1: https://slatestarcodex.com/2017/06/05/is-pharma-research-wor...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592645/
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 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.
Congrats on finding a cure for your ailments
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.
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.
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.
> 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
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
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.
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 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.
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
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 :)
We need to give psychedelics a fair chance, and sure after we can discount them. The article suggests at scale there is potential
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.
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.
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.
Me too
Come on over the skiing is great!
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.
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).
No, I stopped mostly after I’d recovered. And I definitely wasn’t “healthier” then, just addled.
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.
Our selves are not immutable, steady states. Our experiences shape us. It's a lesson learned to guard that carefully and jealously.
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.
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.
“Objection, assuming facts not in evidence”
Evidence based medicine is always better than layman opinions like 'psychedelics are a mental sledgehammer'.
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.
https://www.frontiersin.org/journals/immunology/articles/10....
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.
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...
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https://www.oregon.gov/oha/ph/preventionwellness/pages/psilo...
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.
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.
For frequency, that depends on a variety of factors I suppose.
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.
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.
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.
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.