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This is a first-person account from a psychiatry resident (me) enrolling in a clinical trial of psilocybin. Somewhere between a trip report, an overview of the pharmacology of psilocybin, and a review of the clinical evidence suggesting pronounced benefits for depression.
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Notes -
I've taken hallucinogens many, many times in my life. Mostly LSD when younger, shifting more toward mushrooms as I've gotten older, to entirely mushrooms now in my late 40s. Its the only 'hard' drug I use any more, usually 1-2 times a month on the weekend. Your report sounds like a small amount tbh, mostly based on your ability to actually record the experience. Higher doses absolutely shoot your attention span. The inconsistency of natural mushrooms is a real thing. I'm lucky to have had the same source for a long time now, but even then the same weight batch to batch has noticeable variations in strength. Taking it in a clinical setting sounds frankly horrific. I'm accustomed enough to using psilocybin that I can perform a wide range of tasks while tripping and have never had anything close to a bad trip, and I wouldn't do it in that setting ever. I live on a farm in the country. My primary activity on mushrooms is playing in the fields with my dogs. I think people refer to spiritual or mystical experiences on hallucinogens because we lack other language to describe the experience. I find trying to describe it in words very difficult, like its a category of experience that can't effectively be spoken or written about. I feel this exact same way about the effects of meditation over the long term. We just don't have vocabulary for it in English. As far as enlightenment/ego death/loss of the self experiences, most of the people I've know that have these, and I've also had many personally, are already engaged in this pursuit outside of their psilocybin use. Generally through various forms of meditation practice. Hallucinogens alone generally don't trigger these in my experience, with the massive exception of DMT, which I don't really recommend for beginners. DMT will absolutely slam into the user with ego-death/loss of the illusory self, and though temporary, you don't know that at the time. Its a class apart from other hallucinogens massively altering your thought processes and sensory perceptions.
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I enjoyed this write-up. It was informative and written in an engaging style.
One thing that I think makes psychedelics effective is the work that is done after the trip. Being in a supportive community after the trip seems to produce a lot of benefit. Talking to other people who have also done psychedelics can help you feel a sense of deeper connection. If I was designing a psychedelic therapy trial I would include a mostly peer driven support group for people that have participated in clinical psychedelic trials.
I agree that your experience sounds like the 10mg dose. If you took a higher dose and had a mystical experience or ego death I suspect it may have given you more motivation/desire to make a bigger change to your life. I’m interested in how the results between 10 mg and 25 mg will vary in the trial. I suspect that the higher dose benefits would be more noticeable and would last longer. If the effects from 10mg start to wane it may be an interesting personal experiment to try something approximately equivalent to the 25mg dose.
Thank you!
I think the study does a reasonable job at providing ongoing therapeutic support, but I, idiosyncratically, have never found that therapy worked well for me. I did the bare minimum to keep them content, and didn't notice much of a change. The doses caused immediate and lasting changes in mood, before any followup therapy.
Hopefully, once the results are out, we'll have a proper understanding of the dose response curve at play here.
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I have depression as well, which I blame mostly on a stressful, lonely childhood that gave me attachment issues, using marijuana as a go-to coping mechanism through young adulthood to the present day, and failing to land in some kind of realm of family/community in adulthood to smooth over the various psychological rough edges I have. A little over a year ago I did a ketamine sequence over 7 weeks which I found to be beneficial, but it didn’t quite result in a lasting fix for me, and I ended up going on an SNRI about half a year ago which has felt more reliable in the long-term so far.
The ketamine experience was truly beautiful and fascinating though, and I will probably do it again, but I want to have a significant amount of time between using it to avoid it feeling like a crutch or a recreational drug experience.
I got into meditation in the past, and doing so I feel like really benefited the trip because I was able to go into that zone and really relax, while following different paths my brain was going on. I had explored Jhanas on my own in an amateurish way, and I was definitely able to experience some piti eruptions in ketamine land. I felt a connection to the Eleusinian Mystery rituals, and in moments of awareness I felt a lot of appreciation that I got to live in a time where this mystical state was accessible. It reinforced a feeling that life has meaning, because I was experiencing “meaning” in such a profound-feeling way, that it seems truly odd to imagine a universe devoid of meaning that could produce such states.
All that wasn’t enough to really deeply change me, as I was still spending days alone feeling like my life is still “shit,” so to speak. Possibly that’s because I already kind of knew these things that ketamine was revealing to me through past meditation experiences. Once I was on the SNRI, it felt like the non-marijuana coping mechanisms I had developed were easier to implement, like understanding feelings are temporary and not getting too attached to negative spirals. I don’t have a feeling of why they are easier, they just kind of are, which I’m thankful for, although I’m not sure what the future holds in terms of actually trying to make a better life happen for myself.
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Had a friend who got really into shrooms. It basically ruined his life for a while, and he was only able to recover after he fully quit doing drugs. Went into a sustained severe manic state, spent his entire life savings in short order, lost multiple jobs in quick succession due to erratic behavior, revealed to me detailed plans that if acted upon would have lead to severe social and potentially legal/criminal damage. And the entire time he was subjectively convinced that he had achieved enlightenment and his actions were infallible. It permanently put me off of ever trying shrooms and has made me skeptical of all accounts that portray psychedelics as "harmless".
(Full disclosure, this was confounded by the fact that he was also doing massive quantities of THC at the same time. But then, people present THC as harmless too, so you'd think that harmless thing 1 + harmless thing 2 would be fine...)
I'm sorry to hear that, and I'm glad to hear he got better.
However, the dose makes the poison. I presume he was using very large doses on a frequent basis, in conjunction with "massive quantities of THC". I can't speak authoritatively about the risks of psychosis from the former, at least not without reviewing the literature first, but the latter? If you have some kind of genetic predisposition, such as to schizophrenia, that will fuck you up. And the more drugs you throw into the mix..
In the case of psilocybin, for therapeutic doses, especially under supervision, the risks are minimal. I would never call psychedelics "harmless", but at least in this instance, when compared to how awful depression can be, I felt the odds were in my favor. Even something as 'benign' as SSRIs can cause mania shortly after initiation. Holding out for something that truly has no risk associated with it is a fool's errand I'm afraid.
Like you say though, the dose makes the poison, and there's always a risk. I had a bit of a similar experience with pot to your experience with mushrooms. For a long time I followed the advice of the doctors - I'd always refuse it when offered because of its well recognised effects on people like me. But about a decade ago my depression felt overwhelming and that was around the time psychedelics were showing promising results (ecstacy was also being trialled at the time in Australia, I wonder why it didn't take off like psilocybin?) so I wanted to try mushrooms or LSD, but I didn't know anyone who had access and couldn't get into a trial due to my condition. So in a desperate move to just feel something different, I tried pot.
It has basically fixed me. Ok it was probably the CBD and that's hyperbole, I still have the paranoia and the over inclusive reasoning and holistic bias, but I regret not trying it sooner with all my heart. I have stability, a community I love and who has my back, and I no longer need anti-anxiety, anti-depressant or anti-psychotic medication. But I was never taking massive doses - even when I wanted to get high I'm too paranoid to tolerate the cognitive impact.
Also I don't blame the doctors or anything - they were doing the best they could with the information available to them, and people are unique. But like prima said, it's under-researched. In fact to counter balance what I just said, my brother (who is mentally healthy) also avoided pot for the same reason, but accidentally ate an edible while visiting our uncle and came close to disassociating completely and reckons it took him half a year to get over it. And I've met plenty of schizophrenics who were triggered by pot. It's not a gamble I'd suggest others take.
While I'm glad that weed helped you, I have good reason to believe that that's a rather unexpected/idiosyncratic response.
For most people with depression, I'd go as far as to say it's highly inadvisable:
This isn't entirely causal, as there's some evidence that people with a predisposition towards depression are more likely to try weed in the first place. Yet I think the evidence is there, and in particular, there's little evidence of it helping reduce depression.
What I've heard on the grape-vine is that there are quite a few trials ongoing. I googled it, and they've got some big names involved.
A number of trials have concluded, with, as far as I can tell by eye-balling them quickly promising results.
Unfortunately, adoption just takes time. Not all psychiatrists are as open to the idea of psychedelics as I am. While not a psychedelic, ketamine was only relatively recently approved in the UK for depression, and it's a pain to acquire in the NHS.
Not to mention the lack of a profit motive. Most of them are unpatentable, hence pharma companies aren't really raring to go to produce them.
I've looked at the figures, and that's very rare! Remember, you're looking at schizophrenics who you have reason to believe were triggered by pot. What we ought to be considering are people without known schizophrenia, what are the risks they develop it after trying pot?
That figure is very low. Probably in the sub 0.1% or lower range.
Even within schizophrenics, a study in Denmark found that only ~ 6-8% of schizophrenia cases were induced by weed.
There's also a strong dose dependence here, I would expect that even vulnerable people wouldn't be too affected by a small amount of weed. Unfortunately, potencies have only increased over time.
I wouldn't lose any sleep over it, but I'm not a big fan of weed because it can be habit forming, blunts cognition and just makes you lazy-ass drug if you take it regularly.
IDK, this "Drugs are actually, like, medicine, maaan" has been around for a while, and generally dont seem like someone youd want to end up as. Its getting "scientific" now that the taboo has weakened, but... no shit it looks promising, youre literally trying drugs for mood. If the researcher cant make that look promising, how on earth did he get a PhD?
It also seems like theres some disorder in your post. The last paragraph before "The aftermath:" for example has a lot of redundancy and sounds like it was supposed to be before those other instances. I thought the part about pharmacokinetics was double as well, only realised now that one is about the nausea and one the whole thing.
Is this a serious critique? Like, do you think that psychiatry of all professions isn't aware of the difference between "feeling happy" and "not being depressed"??
The scientists and doctors performing the studies are well aware that many drugs cause temporary and transient elevations in mood. Far fewer cause lasting improvements.
Prescribing cocaine and heroin is, unfortunately, not a viable cure for depression. Just making someone feel euphoria shortly after taking a drug isn't a "cure" or even a treatment.
I don't blame you, because the psychopharmacology is a lot of receptor names and binding sites that sound almost the same and vary in the last few letters or numbers.
Has anyone tried? In the manner of these studies I mean, not by just looking at addicts. People whove done heroin generally report that naive use is an experience beyond anything they had before. I would not be surprised if this influences people even months later. But it also might not, there are always those pescy details. E.g. maybe it overlaps too much with the alcohol high to show effects in our society.
Its more that we have now found multiple drugs with different mechanisms of action, but apparently similar in terms of how they are used and effect against depression, and all of them are used recreationally for their short-term effects. That suggests to me that it works off the recreational bit, and it again wouldnt be super surprising if it did. "Drugs can make you feel better when used responsibly" is hardly a new insight - the entire problem is the way they lead to non-responsible use.
Also curious what you think of this one.
I assure you that they're not effective solutions. Cocaine is highly addictive, and the comedowns more than make up for the very short-term euphoria. Heroin? That's akin to borrowing happiness from tomorrow at a very high interest rate, it doesn't end well.
We've got plenty of studies on the long-term effects of stimulants and opiates. They don't help with depression in any meaningful sense.
I've only endorsed psilocybin in a therapeutic, observed context. It's not a particularly habit forming drug. More importantly, it has a short duration of acute effect, while appearing to durably reduce depression for months after a single dose. It's highly reductive to dismiss such advances as "Drugs can make you feel better when used responsibly".
Addictions aren't made alike. Some can be entirely benign, coffee, as Katja intentionally became dependent on, won't kill you, nor will it ruin your psycho-social functioning. ~Nobody has lost their job or family because they drink too much coffee.
Contrast that to becoming a lay-about stoner, a coke fiend, or a heroin addict.
If were talking about the effect of a ~one time experience, then comedowns arent necessarily relevant. We might imagine for example someone seeing "Wow, its possible to be happy" and that giving him hope in life. That hope might point down the abyss, but thats only measurable when you get there.
But taking this at face value: do you think peoples lives are worse for alcohol? Theres a hangover there too, and in the narrow pleasure-pain accounting, youre not coming out ahead - yet there are many apprently non-addicted people who are using it a decent amount.
Yes, thats the point. The value of the cliche depends on not thinking you can outsmart it.
I am well aware. The link is not directly related to my point here, and I was wondering more about the idea that shes better off for it.
It also remains fascinating, the way people will respond to every part of my comment but the main one. Why do you think apparently different drugs work in such similar ways here?
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Sorry, when I said triggered by pot I meant it made them (according to them) overly paranoid or dip into psychosis and they hated it. Isn't that what you meant when you said:
?
Ah, gotcha.
Cannabis can induce outright psychosis and initiation of schizophrenic symptoms in people with genetic vulnerability towards it. The higher the dose, the higher the risk.
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It’s possible that the THC was the principal culprit. I have witnessed THC inducing acute psychotic episodes on other occasions before. Bit counterintuitive since most people would think of THC as being less “intense” than psilocybin but I suppose the whole thing is under-studied. I’m surprised that the risks of THC haven’t really permeated cultural consciousness.
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Good post but bruh…
Frankly: I hate all this clinical trial bullshit around psychedelics and mushrooms. They definitely have anti depressive effects, but anyone that does drugs knows that the set/setting of these clinical trials is absolutely awful and retarded. You’re tripping and they just have you watching ig reels and tv?
Take 2 gs of real mushrooms and go for a forest walk and think about life. You’ll actually have some real insights about what’s making you that way. Treating these substances like just another pharma substance isn’t the way.
Drug prohibition is a crime against humanity!
We don't really have a good idea how different individuals will react, this guy seems to have pretty badly f*cked up his life https://www.theguardian.com/us-news/article/2024/aug/23/us-pilot-magic-mushrooms-plane-engines (tldr pilot takes some mushrooms for depression, 2 days later is riding in the jump seat of plane [as a passenger, not flying the plane] has a bit of mental breakdown and tries to turn off the plane's engines to wake up, the interactions with the crew are odd and suggest to me more of a break with reality [could be due to the shrooms, or not, hard to say definitely] then a murder/suicide but ymmv).
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I see people out there getting absolutely wasted on kratom, acting like lunatics, wasting huge amounts of money on it, not washing, being aggressive, getting in fights. Maybe drugs should be legal for people who are not idiots.
Kratom provides a kinda-sorta opiate-like buzz the very first few times its used that taper off pretty fast and generally stop around the 3rd-4th use. It is a fantastic pain reliever though, and a godsend for people with chronic pain who cant get medical pain management from a doctor. The pain relief doesn't go away with repeated use like the buzz does.
There is a predictable profile for the people we see who have problems with kratom (I volunteer at a local rehab). They are opiate addicts, usually heroin, pretty deep into it. They get off dope but are struggling with terrible withdrawal. They learn that in the cultures that kratom is native too people use it to get off dope, that it blunts the withdrawal symptoms. This is true, its great for this. Then, the first time they use it they get sorta opiate-like buzz and a lightbulb goes off in their heads: "I've found a loophole! I can keep getting high! I'll still pass my drug tests!" But as mentioned the psychoactive effects fade very fast. This can temporarily be countered by taking more, so they move from the capsules to the liquid extracts then the more concentrated extracts. Still by the end of the first week the buzz is entirely gone. It still offers relief from withdrawal but thats not why they're using it now. This stuff got them high once, why isn't it working anymore? This is where the huge amounts of money kick in. The individual bottles of the concentrated extract cost $20 each or so and they're taking 5-10 a day chasing that buzz that isn't coming back. Way more than they ever spent on heroin (which has been dirt cheap for a while now) Many go back to dope at this point. We see a lot of ODs at this point; having been clean for a while, even just 1 month sometimes, is enough to reset their opiate tolerance but they still dose based on their previous habit, which is now too much.
Kratom is a very effective treatment for pain. Its also very good as alleviating withdrawal, but those first few doses that provide a ersatz high for recovering addicts ruins this use case for some people leading to the observations in the above post.
Only ever saw one guy using it. Young guy, 20-something. A place where I worked part time, one of the temp workers loading the containers. He stank, literally stank so bad I could smell him - I have somewhat impaired sense of smell. Apparently he washed very rarely.. and this was summer.
Later I learned he was homeless, living in a tiny garden colony hut he broke into and even though he could have washed, he didn't. Everyone hated him because he acted aggressive, sometimes talked to himself, kept pacing all the time, was unreasonable... and stank. About every hour he'd mix a kratom drink using a lot of various powders he had there and then drink it. I guess because the labor force situation being what it is, he kept working there for several months.
Once caused a fire alarm because he lighted up a joint or cigarette in the toilets, but the place was so shoddily run they didn't know who was the culprit and he got away with it. Not sure what caused the company to blacklist him eventually.. probably got in a fight with someone.
I really don't think his was 'initial high'. As far as I know, he was persistently agitated this way, which, even more than the smell, caused others to hate him. Maybe he was mixing something else into those drinks though.
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Yeah same with alcohol bro. How many people die from drunk driving every year?
Alcohol is way too widespread to really ban, in addition relatively easy to make at home.
Cannabis is even easier tho...
It's pretty hard to beat, "I left some fruit (that I'm legally allowed to buy and have) in the cabinet for too long."
"I dropped some seeds in the bush someplace" isn't bad...
It's much harder to explain how you legally acquired said seeds. Especially with the effort that it takes to get the kind of cannabis people want (not talking any bullshit about roadside trash grass).
"Roadside trash grass" is about the equivalent of the Jungle Juice you are talking about -- making any kind of decent alcohol at home takes a lot more effort than growing good weed -- which is basically just gardening with extra steps.
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I brought my own entertainment. The study design only offered "relaxing music" and an eye-cover if you were feeling overwhelmed. The music would have worked okay in an elevator or a Thai spa, but was absolutely not to my taste haha.
It's hard to blame them, really. Getting IRB approval for a clinical trial is a PITA on a good day, I strongly suspect that if they wanted to offer entertainment or a walk outside, they'd be raked over the coals, leaving aside the increase in liability and the demands on personnel. I'm certainly interested in trying shrooms in a more congenial environment!
Agreed, clinical trials are just a bullshit way to approach these drugs/medicines imo.
For you personally, yeah go on a forest walk and get into nature. That’s the real way to experience these drugs and most likely to have a positive life changing experience.
If you’re really ADD and need stimulation, maybe just go to a music festival then?
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Can you give us some more details about what the set and setting was for the session?
I had had to head down to London twice to attend the sessions. Beyond that? Not much to say, it was a bog-standard NHS hospital.
You go in, they take your vitals and your measurements, primarily focusing on making sure your blood pressure is okay (psilocybin affects it, not that the risk is notable). By that point in time, you've gone through phone screening, but on arrival, they conduct drug screening. They're looking for any illicit substances that might confound their results.
Once you get the all clear, you swallow a dose, then head to a clinic room. I was alone, but I think I saw a few other people who were probably participants. They had extremely dull music playing, and offered me eye covers if I wanted them. I had a pressure cuff on, with continuous monitoring. A nurse would swing around every few minutes at the staff to make sure I was okay, but eventually I told her I felt fine and she didn't really bother. There was also a psychologist on staff, but I told them I didn't need anything in particular at the time.
Once 8 hours was up (I think they could have let me leave earlier, but I didn't want to risk it since I was unsure about the come down), they took another set of measurements and I was good to go.
Overall, very boring and clinical. Not that there was much else to do, it was a rainy day out there.
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