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Psilocybin found safe for consumption in largest ever controlled study (independent.co.uk)
447 points by pmoriarty 20 days ago | hide | past | web | favorite | 223 comments



Counter-anecdote: I've experimented with this stuff extensively in various settings and have known many other people who did, and in my experience it's unequivocally bullshit.

Here's what happens.

First, any given trip alleviates depression for about a month or two. That makes sense to me in a sense that the word "trip" isn't a coincidence-- a really fun intense vacation in a foreign country also alleviates depression for a month or two. You swear that when you come back things will be different, but then you have to answer slack messages at 9pm, and your project is slipping at work, and your wife is flirting with strangers every time you go to a bar, and well... in a month or two you're back to feeling exactly the same way you did before (until you take the next vacation).

Second, people who discover psychedelics go on a multiyear quest for enlightenment. They keep taking various drugs, keep feeling like they understand things better and better, get sucked into the psychedelic social vortex of other truth-seekers, and generally believe that their life is full of meaning and is going to turn around at any moment. Except by any objective measure they're still nervous wrecks-- they have every physiological symptom of stress and depression, and aside from temporary alleviation of their symptoms (see part one), they always regress to the mean.

Third, after a few years of this people eventually reach a fork. Most people realize that their psychonautic journey is at best leading them in circles, and at worst is causing their life to spiral down the drain. So they give it up, get a job without 9pm slack messages (or find a better way to adjust to stress), marry someone who isn't constantly on the verge of cheating, start doing regular exercise, and generally find a way to settle into a reasonably balanced life.

A small minority of people double down, grow out their (usually grey by then) hair down to their shoulders, go to festivals and workshops, talk of energy and chi and chakras, stare into the eyes of strangers, and touch each other's faces.

Generally speaking, I haven't run into anyone yet who found a third path. So, while I'd be the first to admit I'm wrong and celebrate if this proves to actually work, if I were a betting man I'd bet against at any reasonable odds and sleep secure in the knowledge that my money is safe.


No, your conclusion is bullshit.

> First, any given trip alleviates depression for about a month or two. That makes sense to me in a sense that the word "trip" isn't a coincidence-- a really fun intense vacation in a foreign country also alleviates depression for a month or two. You swear that when you come back things will be different, but then you have to answer slack messages at 9pm, and your project is slipping at work, and your wife is flirting with strangers every time you go to a bar, and well... in a month or two you're back to feeling exactly the same way you did before (until you take the next vacation

Your problems are situational, and when you remove yourself from that situation (using mushrooms or not) your life gets better and when you come back it's worse. It's not the mushrooms fault your life is a mess. Why are you answering slack messages at 9PM? Quit your job or just don't do it. Get rid of your wife if she's making you unhappy.

Do you think that maybe you should be giving your wife your attention at 9PM, rather than slack? How is this not painfully obvious?!

Some people just love misery, it's like - you have identified all your problems but rather than solve them you'll just sit around and point fingers and complain.

What did you expect? You'd take a mushroom and your wife disappears? Or transforms into a princess? You take a mushroom and your slack messages start answering themselves at 9PM?

What did you actually expect from the mushrooms?


It's almost tragic that, perhaps due to the mushrooms, he was able to pinpoint the things that made him unhappy in his life but instead of acting on this newly gained knowledge, points the blame to the thing that made him able to see what the actual problems were.

I've taken multiple times as I find it fun to do but there was this one time I took it when I didn't feel good and just took it kinda out of boredom and it hit me in the face that I was making some major mistakes in my life and I needed to turn these around. I felt awful the entire trip but thanks to the newly gained insights I was able to actually act and change myself for the better. LSD never changed any of my problems but it made me aware what they actually were in a more concrete sense.

To put it bluntly I was unhappy without really knowing why, and after LSD I was unhappy and knowing why. I don't believe psychadelics will ever resolve your problems, you just gain new insights on your issues and it'll still be up to you - in a sober state I presume - to act on these insights.


Brutal honesty at its best. If everyone had the guts to talk this tone to their boss the world would look a lot better.


Well there is a saying "It is easy for a single man to divorce a wife". I am not sure his suggestion is practical also tone is terrible. I hope they can cope with other people who are being "brutally honest" with them being a jerk in real life.


I read love your wife more in the morning because her soliciting other guys in front of you is the most obvious sign she will give before filing for a divorce herself.

If no one tells you this , you can't solve problem number one. Problem number one always results in no sex followed by a system break down hence the princess comment. In the western society women initiate 2/3 of the divorces.

GP is nuanced giving a helicopter view on the personal projection at hand so it doesn't dilute the actual news brought here to light . If this tone sounds offensive we could ask HN to introduce emojis.

Someone once said something about a hammer the same applies for the mushroom.

Edit: your original comment included in Turkey we have a saying.


> In the western society women initiate 2/3 of the divorces.

Interesting. Source?


I found this by quickly googling https://www.sciencedaily.com/releases/2015/08/150822154900.h... but there are more sources as well. From my anecdotal non-scientific observational experience it seems completely doable.


Yep I can.

> I am not sure his suggestion is practical

So what's your solution? Just live in misery all the time because doing the easy thing is easier than doing the correct thing? Avoid immediate discomfort in exchange for long term happiness - what terrible advice. No wonder these people are depressed.

You only get to live once, and I cant imagine anything worse than rotting away because you dont have the balls to stick up for yourself - sitting there at 9PM answering slack messages rather than just saying "I'm off the clock, go hire more people if you want 24/7 support".

Make love to her and save your marriage or break up and move on, just don't sit in resentment filled limbo, watching her clearly unhappy and flirting with other men --- then act surprised and betrayed when the thing THAT YOU CAN SEE MILES AWAY happens. He can see the unhappy future approaching and he's still not acting? Why? Because he is in love with misery like my post says.

Except when he does the mushrooms and they cheer him up a bit and give him the clarity and happiness to fix it. He still has to do it himself though


I found that post aggressive, biased, and kinda missing GP's point.


What was good about that post? It sounded like gross generalizations and deep seated resentment, with not a touch of “honesty”.


While this rings true, consider we can pursue this conclusion for just about any instance where depression is reported. We can say: why aren't you drastically shaking things up? Why are you not making changes of extreme consequence that will completely change your life in unpredictable ways? Change frightens people, but some have more to lose than others. A few years before I met my SO, I had broken up with a partner of over 3 years and changed jobs, then subsequently fell into sleeplessness and depression for a year. Change isn't necessarily free, though probably worth it if it's under serious consideration.

In my observation the perpetually depressed are often (no, not always, but very often) home bodies who barely leave their domicile and spend ample amounts of time on social media, staying up late mindlessly scrolling through their phones. There are simple but perhaps difficult changes to be made here.


Yes - and it's mushrooms that will knock you out of this funk.

The mushrooms fixed him for 2 or so months. During that time he should have woken up and sorted his life out. Thats enough time to start exercising, having the conversations at home and work.

You dont have to solve everything all at once, but fixing depression is a cumulative process where even small changes in diet, exercise and environment will compound over time and put you in a better place.

The mushrooms will show you the answer, but it's up to the individual to act.

Did you notice in his post he didn't describe what happened when he was cured in those two months? No, straight back to finger pointing and blaming everyone else.

He needs to hear the blunt truth : maybe, just maybe, it's his fault. Then he can take more mushrooms and work on fixing it, rather than expecting them to be a magic bullet.


I've tried shrooms, I'm not sure they show anything much the same way anti-depressants don't show anything. But they may be a useful stepping stone to spur change and eschew learned helplessness. No one can alleviate your depression but yourself.


Also, drugs only work in combination with talk therapy. It's amazing how many people argue for everything under the sun except talk therapy.


Talk therapy is expensive. $150/HR is about the base rate for my city. An average treatment regimen is 3x1hr/wk or $1,800USD/mo. That's 68% the 2016 individual median equivalent annual income. Therapists qualified and stable enough to treat severe illnesses are exceptionally rare. Rare enough that they can charge a multiple of the rate I quoted, while maintaining a calender as full as they like and a waiting list of willing clients, and can choose to accept or refuse insurance on a whim.

It's amazing how many people casually bring up the wonders of talk therapy without noting any of the confounding factors the patient must watch for while they pay out the nose for therapy that may end up having detrimental effects. An average or worse therapist for anything but textbook cases are liable to cause more harm than good.


Not having thousands of dollars you may have otherwise to use for various productive purposes had can also have a detrimental effect on health.


Thanks! That's certainly one of the confounding factors I had in mind when I was writing this. The same goes for traveling to and fro meetings. This is especially painful for hardworking yet poor mentally ill and unskilled workers trying to get their life together. Overcoming mental illness, childhood abuse, medical issues, witnessing or being a victim of a crime, and bettering oneself, oftentimes several of these at once, is a Herculean feat. Asking for help does not mean someone is lesser. In fact, by not helping someone in need they're less likely to ask for help before they do something permanent. For some all this work proves too difficult. For so many reasons.

Most Americans are scraping by with medical, addiction, or mental issues on top of being underpaid, under educated, overworked, and priced out of necessary services like mental/health/child care, housing, and transportation.

It's no wonder so many articles and studies bemoan the current state of affairs.


The scheduling is even worse for free services where hours the services are offered are limited especially if you're holding down a job, and once you make it work by waking up a couple hours earlier thna normal and jumping through a bunch of hoops... the care is temporary and you need to find something else in a few months.

If anything I think part of the value of seeking out mental healthcare is symbolic. I.E. it's so difficult and costly you convince yourself that you must really want to get better, can work hard, and that something so burdensome must work or nobody would bother with it (a sort of placebo effect). Yet it's easy to get jaded and easy to find yourself going through some ineffectual therapy at great personal cost.

I also think that people are really hung-up on two specific approaches, namely talk therapy and drugs, when they can simply not be cost-effective. It's really costly to put a specialist through years of school, and heat up those counselling offices, and all of that. If you're poor enough that money can make a HUGE impact on the diet you can afford and the exercise you can get. People seem to have this funny idea that somebody living an impoverished miserable life will be happy if somebody says some kind words to them and drugs are altering their neurotransmitter levels.


You're getting at what's known as rotten life syndrome[1]. The themes are consistent across every demographic. When someone is underemployed, overworked, under housed, impoverished, starving, a victim of crime/persecution, etc then they will manifest the symptoms of various mental illnesses depending on what's going wrong in their life. Therapy cannot be useful if the basic life of a person is unstable. Yet these people are told they aren't working hard enough, they deserve what they get, etc. It's absolutely ridiculous. We have the means the house, clothe, feed, and care for everyone. Our electorate has, and probably will, continue to get away with, misappropriating these resources for their own gain, at the cost of countless human lives.

1. https://www.stmartin-in-the-fields.org/mental-health/


Why do you say that?


You sound live you’ve never done this, let alone any other shit.


I have done a buttload of LSD, not so much shrooms but also some.

- I never thought it would cure my depression, but then again I have never seen my depression as something to be cured. It has helped me understand that my depression is a reasonable consequence of how I live my life and it also made me understand what choices I would have to make to change it.

- It never made me feel like my life is full of meaning - it actually showed me how the lack of meaning in my life is related to my depression. It also helped me understand the complexity of meaning and made it clear to me what would be needed to have a meaningful life.

- Psychedelics has not made me worse at my job, it has not caused me to spiral, it has not driven me to other drugs.

The experiences I have never once made me want to grow my hair, nor go to festivals, nor talk of energy and chi and chakras - and in general I avoid taking it with or close to other people. I don't now how you got to that at all really but I think it was bad influences in your life more than the psychedelics.

If anything my psychedelic journey has made me maybe more conservative than I used to be and I am less likely to believe in any kind of woo like chi and chakras than I was before I took it.

I would not really recommend anybody take LSD or psychedelics - but I think it have had a very positive influence on my life and if anything I regret not taking it more often.


This has been similar to my experiences; definitely less liberal but not explicitly more conservative, more technocratic perhaps.

Also became increasingly atheist & materialist after a few times. Don’t move the mental furniture around if you’re already content with the brain-room, I’d say.


I think this is relevant https://news.ycombinator.com/item?id=21590028

I see what you mean and you're certainly right for a segment of the population that seems to get caught on the high without much skepticism of it.

That said, it is in not bullshit, and its not bullshit precisely because of what cite as being the bullshit: People take it and get the same benefit as going on a multi-week vacation. At least that can happen. Given you report your own experimentation, I'm curious if you mean psychedelics as a whole or specifically psilocybin? I'm curious of this because while I have experienced significant change in my worldview as a result of LSD trips, I had none of the same from shrooms. They're fun for sure, but I felt the next day the same I would if I spent the same time smoking cannabis. Family members of mine also have had shrooms and similarly found little to no productive value in them, but have found value in LSD. The temptation to suspect a genetic link is obvious, but of course thats just my n=1. When on LSD I tried a sort of self-therapy that seemed extremely successful, thinking through issues and considering new narratives of worldview. I've also had LSD trips where I didn't attempt such self-therapy, and found that I woke the next day feeling no different. I also tried self-therapy on shrooms and thought it was working during the trip, but woke up feeling just the same as before. So I think methodical thought through whatever is making the person feel depressed is absolutely necessary if any success is to be expected.

I suspect that many of the people who have gotten the best of the benefits of psychedelics and led successful lives are just not so vocal about it. I feel LSD has majorly helped me, but I'm really not about to go preaching that, because while it helped, it wasn't the only component. I also made the choices to use what I learned on it and change how I behave.


I mean, temporary alleviation of symptoms can be extremely valuable.

Think of how many people are on SSRIs that have mixed effectiveness, side-effects, and have to be taken daily. Then compare that with a treatment that you do once a month and whose main side-effect is a heightened sense of empathy. Even if it doesn't permanently get rid of depression and anxiety, and solve all of your underlying problems it's still a big step forward relative to the current state-of-the-art treatments.

I can speak to how nice it is to just feel fine for a while and get some respite from a constant feeling of fear and anxiety at everything. It's a world of difference, and could easily be the difference between someone not even being able to get out of bed, and actually taking a crack at doing things.


> First, any given trip alleviates depression for about a month or two.

That's why they are trying to turn it into therapy instead of advising sick people to experiment wildly.

They know there's an effect, now they know it's safe. What's left to establish is what's the most efficient protocol for using it.


First of all, there is a wide delta of difference between taking these substances recreationally and in a clinical setting. Any clinician involved with these trials is not going to equivocate their use in treating depression with your weekend in the woods with your friends.

Second if we are talking recreationally I have met many, many people on a third path there: the understanding that psychedelics offer a beautiful alternate window with which to perceive things and they can tend to have a heightened awareness and appreciation while otherwise being just like many in that they answer slack messages or [insert mundane work task here].

Thirdly the mind in question is more important than psychedelics or slack messages. One can view either as a hellish prison or a wonderful gift, and in either case this perspective is likely to prove itself out. There is no magic cure to gift inner peace, nor is inner peace at all waking hours a realistic or worthwhile goal for anyone. This does not make psychedelics "bullshit," it means you need more to cultivate a rich inner life than a few altered state experiences. This should not be surprising (though to be sure it is quite often).

Fourthly, when you say:

> Most people realize that their psychonautic journey is at best leading them in circles, and at worst is causing their life to spiral down the drain. So they give it up, get a job without 9pm slack messages (or find a better way to adjust to stress), marry someone who isn't constantly on the verge of cheating, start doing regular exercise, and generally find a way to settle into a reasonably balanced life.

Have you asked these people how they came to their better life there, their job without a 9pm slack message, their healthy marriage, healthy lifestyle, etc? Many would likely attribute at least part of this found balance to their experience with psychedelics. Many people in these trials, a majority in fact, count these experiences among their top 5 most profound life experiences. That's astounding, and anecdotally I've met many more who fit that bill, and of course there are other famous cases who parrot this like Steve Jobs. Psychedelics are not an answer, but they often do illuminate where paths were previously hidden.

I believe your cynicism has sliced off only a portion of the truth here and tilted focus in the wrong directions.


> "I believe your cynicism has sliced off only a portion of the truth here and tilted focus in the wrong directions."

I think his cynicism is completely warranted considering how many people are starting to view psychedelics as a panacea.

Do psychedelics offer an experience that could be part of, or even a spark a greater shift? Sure.

Could psychedelics provide temporary relief from things like depression and anxiety? Sure.

Do most people approach things that are talked about as a solution to life's most difficult problems in a moderate way? Very rarely.

Are there VERY REAL and SIGNIFICANT downsides to the misuse of psychedelics? Absolutely. Bad trips are very real and with real, long-term consequences.

From my experience with these substances and from my observations of many people who have also used them, I think we should approach the subject from a cautious point of view at the very least. We can throw around studies all we want, but as you pointed out, these are almost all done in a CLINICAL SETTING which is probably the most relevant aspect to the outcome of psychedelic experiences.


I haven't heard almost anyone say its a panacea, but are still advocating for their consideration as there's plenty of people who will advocate its always a bad idea.


All of what you said here is true, but that does not equate to "bullshit." Some level of skepticism is of course warranted. Complete dismissal is not.


who is saying "bullshit"? I think I am making a pretty reasonable argument that seems to fit into "Some level of skepticism is of course warranted".

I'm so sorry you are being downvoted. The current enthusiasm for psychedelics is making it very difficult to talk publicly about all the dimensions of a highly nuanced topic.


Third path: It's a fun way to pass the time once in a while.

Fourth path: You learn what you need from it, that the world is just various inputs into your brain and gives you perspective to slow down.

As an aside, your post is full of negativity. I hope you get the help you need somewhere.


Every tool has it’s appropriate use - there is a middle way.

I sleep well, eat well, exercise, occasionally micro-dose, and if my brain gets in a really bad place I’ll do a huge reset trip. I’ve been doing this for 10 years and I’m the happiest I’ve ever been.

Temet Nosce - Know Thyself


If your life sucks, depression is a completely reasonable side effect. Clinical depression is a different beast -- even on great days, free of external stressors, you're wont to feel miserable.

Mushrooms won't fix your life. But even your anecdote suggests that they can provide a brief window of clarity. In that window, you can choose to make changes in your life, but making big changes is risky and typically quite difficult. But for folks with clinical depression, these treatments might be a game changer.


Counter-counter anecdote:

I was just listening to an interview[1] with Dennis McKenna[2] (brother of Terence McKenna[3]) in which he said:

"If I'm going to take it [a psychedelic substance] I'm going to pay attention to it. It's sort of like you have an opportunity to sit with someone who's very wise and they have stuff to tell you and so they deserve that respect. That's what's changed. I give it my respect.

"And sometimes people say, well, you've been doing this 50 years haven't you got the lesson yet? .. there's one perspective that says 'once you get the message hang up the phone'.

"Well, maybe I'm a slow learner but I'm still learning from these things. They're not like an answering machine. It's not like there's only one message.

"It's like if you had a mentor, a teacher, someone who you respect you're not going to reach a point where you say, 'well, basically I've learned everything you have to tell me so thank you very much and I'll be on my way.' Chances are they still know more and they always will know more than you will know.

"Every time I take ayahuasca or mushrooms I learn something new or I am reminded of what I've forgotten, what's easy to forget in the day-to-day hustle of life. I just feel it's still valuable. In some ways it's a touchstone. It's a way of getting back to that place, that sacred space, sacred time environment where you can remind yourself of the eternal truths."

Second counter-anecdote:

Ram Dass[4], in his 80's after suffering a stroke, when asked in an interview that I can't find at the moment about what LSD has done for him replied "I'm happy. I've had a stroke and I'm happy. That's LSD."

[1] - https://www.youtube.com/watch?v=KGYm5OdvwNs

[2] - https://en.wikipedia.org/wiki/Dennis_McKenna

[3] - https://en.wikipedia.org/wiki/Terrence_McKenna

[4] - https://en.wikipedia.org/wiki/Ram_dass


I think referencing the leaders of the psychedelic movement would be a pretty biased argument for psychedelic use. Survivorship bias would also be a factor.

I want to echo the sentiment of the OP - I have yet to meet someone who does not go down one of the two paths described. Either they continue to do various psychedelic substances over the years claiming to have solved all their problems while a cursory examination shows their lives continue to be a mess.... or they stop looking at it as a panacea and start making meaningful changes in their lives that actually have a long-term positive impact (this is my own experience).

I don't have a problem with using psychedelics IN A RESPONSIBLE WAY for short term relief from symptoms of a greater issue that actually requires concrete, meaningful action to address. Maybe the relief, from depression for example, is enough to find the motivation to take those actions. HOWEVER - most people tend to be very black and white in their thinking and don't see it as treating a symptom - they see it as a solution to all their problems. You see it over and over again with various approaches - fasting, keto and psychedelics being the current fads.

There is no panacea for living a healthy, fulfilling life. It takes conscious, persistent shifts on many different levels. There is no cure-all. There never has been, and never will be.


Sounds exactly like running in circles...


>in my experience it's unequivocally bullshit

>[trip compared to] a really fun intense vacation in a foreign country also alleviates depression for a month or two

I think these two are confusing statements if read together. That being said, I think I understand what you mean.

From the info I’ve gathered, almost everybody agrees with you. It’s not a magic cure. Sure, someone might argue it is but you’ll find that person everywhere. But for someone with severe depression who can’t see beyond the wall could be really valuable experience, since otherwise couldn’t go (or even afford) going on a very intense vacation in a foreign country.

Sometimes you may need clarity to deal with the problems that otherwise depression wouldn’t let you (or wouldn’t even let you see them). But I guess (because I haven’t tried this, but read a lot) it’s all about the mindset you approach this.


That's a hell of a generalization from an anecdote.


I know right - it's an epic extrapolation.

I drank a beer 20 years ago and now BAM, cancer. We should ban all this cancer causing beer.


IME, my various neuroses are correlated with my productivity. Sure, I can eat shrooms and feel better, but I'm too happy and mellow to get anything done. Soon, the stress from not keeping up builds and I'm back on the wheel again.

I did have some luck using mild amounts to combat the negative cognitive effects of smoking too much pot(mostly verbal deficiencies), but in the end it was better to just stop smoking pot.

I'm glad we're finally discussing the potential of psychedelics. I think they will help researchers understand what makes us who we are. I know we're better off not locking people up for using or possessing these substances. I do not think that the personal use of these drugs will notably advance society however.


> Sure, I can eat shrooms and feel better, but I'm too happy and mellow to get anything done.

That should tell you about the true nature of your motivation.

If you are only productive when you are unhappy, it likely means that you are trying to motivate yourself with negative thoughts and judging and compulsive feelings, it means you do productive things while using a stick to constantly keep yourself in fear of hitting yourself with it if you're not productive. If anything, this is the message the mushrooms are trying to tell you. But it is still up to you to change your patterns in response to that message.


For a lot of people when it "works" for them is when they discover they no longer need the drug at all and feel they know more about themselves. You describe it here:

"Most people realize that their psychonautic journey is at best leading them in circles, and at worst is causing their life to spiral down the drain. So they give it up, get a job without 9pm slack messages (or find a better way to adjust to stress), marry someone who isn't constantly on the verge of cheating, start doing regular exercise, and generally find a way to settle into a reasonably balanced life."

Perhaps this period of self examination is what leads so many to such similar conclusions?


I took a lot of psychadelics, stopped, and started using them again rarely. I'll occasionally take extremely small doses to self-medicate acute depression but it makes me overly impulsive.

I read a lot of experiences from people who went down both the paths you're talking about so I just avoided them. Rather than not using and considering it inevitable that for years I would be using psychadelics in a degenerate way. I approached them with the mindset that they are a tool to look at problems from a different perspective and accelerate certain forms of thinking. However this tool, independant of actual self-improvement, was not only useless but self-destructive.

I ended up having subjectively worse mental health after the psychadelics. Although the psychadelics were a desperation attempt in the first place so take this with a grain of salt. At the same time my life OBJECTIVELY became much better. Better diet, more exercise, more social life, stronger, more cash, all that jazz. I basically turned around a situation where I was completely trapped in poverty and despair to one where by a good number of measures I was pretty successful. So I do find it interesting to read about how people who take psychadelics are all deluded into thinking they're doing well when they're doing awfully. Since that's precisely the opposite of what I experienced.


I think I understand your sentiment when applied to a subset of people. Specifically people who’s lives may be a mess and they are leaning too heavily too drugs to change their lives. I don’t think psychedelics alone should be used for that. I feel that people (yourself as well) are being far too focused on psychedelics usage for healing/treatment. There is another aspect to psychedelics where you literally experience something transcendental. that experience alone can be humbling, terrifying, amazing, or any other range of feelings. It can certainly be learning. Something that you perhaps can’t even put into words. And even many of the experiences that you are be able to somehow find words or metaphors to describe, the new perspective(s) can be interesting at worst case. They can show you knew ways to think of problems or even serve as new creative ideas for art, and of course cause you to make various changes to improve your life. I could probably easily name 100+ interesting thoughts that psychedelics have showed me and I certainly haven’t dabbled anywhere close to 100 times and don’t really feel the need to.

There is also of course also doing them for the pure enjoyment of them. For example, I’d wager many people would prefer a psychedelic experience over being drunk. Much in the same way that people may prefer marijuana over alcohol.


It is not a cure for the root cause of anything.

I like to think of it as a tool that helps you get out of writers block. You still have to write once you’re unblocked; it won’t be able to write for you.


First,hope everything is ok with you, if not, I hope it will be :)

Second, you're talking about curing the disease and I agree with you 100%. I don't like or promote psychedelics but from what I understand they are in this context to be seen as solutions to symptoms much like antidepressants and pain killers where they merely give you enough breathing room to where you can focus on fixing the root cause instead of chasing after ways to alleviate symptoms.


I think the enlightenment of psychedelics is often oversold, but it isn't naught either. These experiences are one way of proving to yourself that your perceptions are not a clear window, they're more like stained glass. The majik is when you realize how to mold and shape that stained glass such that it leads you to make better decisions, and gain more control over your own experience.


The drugs are not supposed to get you there. They are supposed to show you the territory, lift you, temporarily, out of the slime and muck of the dark age of materialism.

The rest is up to you, whether it's the third path, fourth path, or the umpteenth path.


What exactly do you expect was going to happen? The entire point is to identify the issues so you can take action. You seem to know what the issues are already. Also, there's a good chance your wife is already cheating on you. Maybe those late slack messages have something to do with it.


Lol. I’ve done a ton of psychedelics and now I’m just one calm and cool cat. The drugs taught me to work my science job, never speak outside of work, ride my skateboard, play video games, don’t get involved with women, sleep a lot, eat good. It’s all the benefits of ego death.


I don't think everyone who has taken shrooms/psychedelics is taking them to alleviate depression. I mean not everyone has depression in the first place and I'm pretty sure non-depressed people would still feel the effects.


My favorite aspect of Psilocybin is how it makes everything seem so mathematically connected.

The affects on one's emotional state is surprising. Probably a good thing, but to me secondary.


Take the red pill - go to the gym and get jacked. It will solve many of your problems.


Do both! But I will certainly always advocate for increasing physical health. It has an absolutely amazing ability to increase your own happiness and mood. I can confirm with myself as a single anecdote. :)


There are so many interesting ways of getting / staying fit. Rock Climbing, Skiing, Mountain Biking, Hiking. They often involve going to beautiful locations or at the very least getting out of the city.

Why you would suggest the gym (repetitive activity with a load of other sweaty people) is beyond me...


Because high muscle mass and low body fat is universally what women want/find attractive.


What on earth are you going on about


Yes no doubt they’ve found it safe when allowing for the effects to fully wear off and at a certain dosage. Chemicals of this class are similar in structure to serotonin itself and do the opposite of SSRIs. This would mean the therapy is meant to go straight through problems regarding depression not simply make one happier. Generally speaking psylocibin is more prone to culminate in a really bad trip than delysid if the participant doesn’t have their mind settled! This is also dependent on how it’s isolated and from what. Oregon azurescens raised in wood chips is much more mellow and yet stronger than other varieties for example. Migraines are an extremely good use case but factors of depression can vary so wildly I’m not really convinced it would be a silver bullet. If nothing else works then maybe it would do the trick. Don’t play with magic unless you want to be tricked.


"Generally speaking psylocibin is more prone to culminate in a really bad trip than delysid if the participant doesn’t have their mind settled"

One of the most interesting interviews about psychedelics that I've heard is one with Stanislav Grof, who personally supervised over 4,500 LSD sessions throughout his life (many of them during his research in to its effects, back when LSD was legal) and at about 1 hour and 56 minutes in to the interview he said:

"If somebody has a bad trip that means they are dealing with a difficult aspect of their unconscious and when it's coming up, it's coming up for healing... people can benefit from bad trips. I saw many of those situations where people experience what they would be hospitalized for in the psychedelic sessions, and if we stayed with it, it would actually be a major healing, a major transformation."[1]

I also found in my own experience that my bad trips were the ones that I learned the most from and the ones that I found the most beneficial, because they would force me to face my demons and other major issues that I would avoid facing in my sober state of consciousness.

Interestingly, the study this HN post links to seems to refer to something like this:

"Recent work has sought to develop and validate a measure that is sensitive to difficult or challenging psychedelic experiences (Barrett et al., 2016; Carbonaro et al., 2016) and there is some evidence that the intensity of such experiences is predictive of positive long-term outcomes, whereas the duration of struggle is predictive of negative outcomes (Carbonaro et al., 2016). This is presumably because the successful resolution of conflict brings with it, insight and relief, whereas the failure to breakthrough perpetuates suffering."

My impression from listening to and reading many interviews with veteran psychedelic researchers (who did studies with pretty massive doses of psychedelics back in the 60's) is that they seem to believe that an inability to "break through" was due to having too low a dose, and I wonder if that's the case in the unresolved difficult experiences this study refers to. On the other hand, too high a dose of psychedelics can result in post-trip amnesia (and current psychedlic researchers seem to be erring on the side of caution and give moderate doses). So there's probably some good middle ground.

[1] - https://www.youtube.com/watch?v=3mdYUmvTeig


My bad trips made me learn to stop tripping. But my good trips made me learn a whole lot more about what might have been possible for myself and my social anxiety after I stopped. I'm still learning lessons related to those insights but compared to the confidence I had on a trip versus the confidence I have now I say I'm 70-80% at that level.


Just want to point out you are taking the chemical at recreational doses and not therapeutic doses. This is why a professional administrating the drug is key. Look at it this way, Zoloft may give you a bad experience but not the same bad experience at 5mg vs 100mg. You can recognize the bad experience and work towards something else at 5mg vs 100mg (or replace with your favorite drug/dose) where you may end up in an outpatient hospital.


The point I'm trying to make is that for all the risks I was taking none of the outcomes were psychologically unrecoverable or fatal. Using the word "bad" was just pointing to the class of experiences that people on the psych might consider, "not pleasant", but "not pleasant" doesn't mean "not valuable". Quite the opposite, I learned from basically every experience both through its intrinsic and extrinsic qualities.

Giving psychedelics the psychiatric treatment and connoting that there are hard distinctions between "recreational" and "therapeutic" doses for some of these drugs fundamentally misunderstands them. I had therapeutic effects from "recreational" doses.


You can say the exact same thing for Zoloft. If you took a single 100mg dose you will notice the effects. But the line that crosses therapeutic to recreational (yes SSRIs are abused recreationally but are very short lived) is somewhere between 0 and 100mg and differs based on your biological makeup. Clinical trials and reports from prescribing psychiatrists helps find that hard distinction..


They can track and establish the base rate of such effects conditioned on a random population to blur the role of one's "biological makeup", and then apply value judgements as to what doses are useful for their purposes, yes.

In that sense if you're allowing whether or not a drug is recreational to depend on a person's makeup, how could you have known I was taking a recreational dose? Could bad trips not also occur at lower doses considered sub-recreational if a person is particularly sensitive? Likewise what happens if the drug only ends up benefiting a person past the point where they also have hallucinations as a "knock-on"?


>In that sense if you're allowing whether or not a drug is recreational to depend on a person's makeup, how could you have known I was taking a recreational dose?

that is literally the point of a psychiatrist. there is only the law preventing psychiatrists from administering psychedelics like LSD in the same fashion. there are natural practitioners who do this for e.g. marijuana today.

if someone has an adverse reaction (bad trip) then the doctor usually alters the administration of the medicine in some manner (Lower dosage, increase dosage, change medication all together etc). but to say that there are only recreational doses for illicit drugs and there is no method to validate potency in human consumption is disingenuous.

a drug is a chemical. our body is nothing but a chain of chemical reactions. modern medicine and science has come up with a pretty good method of determining dosage


Now that mainstream club drugs such as MDMA, Ketamine, and LSD/Magic Mushrooms are finding their way into therapeutic usage. I'm wondering if and how governments will change the current narrative about "all drugs are bad for you".

Edit: I'm not advocating recreational drug usage. Just saying, that if mum is on magic mushrooms and studies like these have established safety dosage and clear therapeutic benefits. You can't really tell your teenager that they are going to go crazy if they try some.


> I'm wondering if and how governments will change the current narrative about "all drugs are bad for you".

Caffeine and alcohol are "drugs". But they aren't drugs. In the same way, I think we'll the label released from accepted substances, while remaining attached to unacceptable ones.


After Snowden's revelations, I also wondered if the government would change it's practices.


I don't think Psilocybin mushrooms or LSD are used as a club drug.


They're a party drug for sure. LSD is great for festivals, and though I've never done shrooms, I know my friends have gone to shows on them.

In fact, I'd say LSD is used more as a party drug than it is used for anything else.


I don't know about that. All my psychonaut friends would rather lay out in a field in the sun than hit the club on a trip. Festivals are different though.


It also certainly depends on dose. I know after my first experiences my initial thought was that there was no why in hell I’d try that at a festival, but then I saw so many people/friends doing it and decided to give it a try. Was definitely mind blowing.


Where are you getting this from? The only psychedelic I've ever seen people take before clubbing is 2CB.

Festivals are different because there is lots of space. Clubs are too compact and contained for LSD, can make people claustrophobic.


Of course they are, all the time


Perhaps not club, but most definitely festival


There is an entire genre of club/nighttime music called “acid”, fwiw.


Oh they are for sure, they are a big part of club/electronic music culture (both for the producers of said music, and the listeners) - or at least have been in the past - I'm sure trends change.


I think it depends on the definition, https://en.wikipedia.org/wiki/Club_drug includes them


As long as it's popular understand and opinion of drugs, then ultimately democratic/representative governments are going to have to start changing the narrative if they want to stay in office


MDMA, Ketamine and LSD sure, but mushrooms have been in use for spirituality far longer than mainstream clubs have even been a concept.


Right, but they haven't been classified as an illegal drug in most countries until recently.


And K started with medical use.


They wont change it, as they will be paid lots of lobbying money to not change it.


Yes. Unlike alcohol, there is very little money in those drugs. Most of them aren't even addictive!


Yep, and big pharma dont want people having access to cheap non addictive drugs. It not good for their shareholders. I could never work at a drugs company.


Uhh would definitely never recommend taking LSD or shrooms to go clubbing.


I'm personally excited to see what sorts of new treatments will come out of using psychedelics medically. I've always been on the skeptical side of medical marijuana usage in all but the most extreme cases, but I have a feeling that LSD and psilocybin can really provide mental turning points and help people break out of depression.


> I've always been on the skeptical side of medical marijuana usage in all but the most extreme cases,

Really? I've always found the milder claims fairly believable (fighting nausea or chronic low level pain relief). As an anecdote, I can attest to dealing with kidney stone pain well (rather than stopping the pain it reduced how much I noticed it) and it ended up more effective and felt less dangerous than the opiods I had used in the past.

Some of the more "miracle" claims, however, seem pretty suspect to me and I'd want some reliable reseach.

What makes you skeptical of so many claims?


I've definitely experienced the anti-inflammatory properties and the anti-nausea effects allowed my mom to keep food down while going through chemo. It was the only thing that would take away her nausea.

I do agree with the parent poster about the more miraculous claims though and I think, personally those more miraculous claims create skepticism for the actual benefits.

I kind of wish everyone took a more level headed approach to drugs in general. Every drug out there has some benefits and drawbacks. Without proper study, we're potentially missing many benefits and won't fully understand all the drawbacks.

This includes approved pharmaceutical drugs too. Too many drugs get rushed out without fully understanding the side effects until people start suffering or dying.


I tend to agree with grawprog. I think it is powerful in cases like chemo (I had a friend who used MM on chemo and it curbed his nausea like no other drug could). For chronic pain I think it is better than opiates, but I'm not sure that the side-effects out-weigh the benefits. My mother has knee issues and is a MM user, but the marijuana is not helping at all with the root cause (she is severely overweight at 5ft 4in and over 300lb). Mainly I think that I see medical marijuana as being over-prescribed where there are better solutions. I personally don't have any problems with marijuana overall as I am a recreational user.


The treatment of Dravet syndrome with CBD seems to have genuine damned near miraculous results.

And yes, the pain relief is very real.


Personally, I'm a skeptic that 1. CBD+THC offers any additional medical† benefits over CBD used alone; 2. that it makes any medical sense to prescribe a (non-dose-controllable) plant over a pill, or at the very least an extract with tested dosage. I'm not skeptical of the medical benefits of (some of) the compounds in marijuana; I'm just a skeptic of prescribing marijuana itself as a way of delivering those compounds. It's like prescribing willow bark for a headache when aspirin exists.

† For what it's being prescribed for, I mean—pain, nausea, anxiety, etc. THC, in its function as a psychedelic, may function as a treatment for certain psychiatric disorders (i.e. for much the same purpose LSD/MDMA/etc. are being investigated for.) But nobody's prescribing medical marijuana for this use-case right now; they're prescribing it for things where the presence of THC seems pretty irrelevant to the goal.


> I'm a skeptic that 1. CBD+THC offers any additional medical† benefits over CBD used alone

You shouldn't be, because empirical evidence shows that there are.

CBD's most overt therapeutic effect is mediated through action at 5HT1A autoreceptors and allosteric modulation of mu and delta-opioid receptors, whereas THC's MoA is mediated through CB1 agonism, to a lesser extent CB2 agonism, and to a lesser extent than CBD, allosteric modulation of mu and delta-opioid receptors.

THC has anxiogenic (and paradoxical anxiolytic) and psychotomimetic properties, and has the side-effect of inducing schizophrenia-related disorders in some people. CBD's action at 5HT1A receptors both induces an anxiolytic effect, and reduces the symptoms of psychotic disorders.

A combination of CBD+THC can reduce the negative side-effects of THC used alone, and CBD alone does not have the same effects as THC or CBD+THC. There are studies that document the synergic effects of combined cannabinoids versus isolated cannabinoids.


I agree with everything you said, but you didn't say anything that relates to medical benefits of THC for any specific use-cases. Certainly CBD+THC has synergistic effects—it gets you more high—but does it relieve more pain, or fight more nausea? Because those are the criteria the treatment is being graded on here.

I'm not skeptical that THC does anything; it certainly does. What I'm skeptical of, is whether marijuana has the particular medical benefits it's prescribed for in part because of THC, rather than despite THC.


> I agree with everything you said, but you didn't say anything that relates to medical benefits of THC for any specific use-cases.

I did, though I wasn't explicit. CBD has no discernible effect on CB1 receptors, and produces no anti-emetic effect. THC's CB1 agonism is directly responsible for its strong anti-emetic effect. CB1 agonism also has effects on pain perception and processes in the gut.

CBD has no discernible effect on CB2 receptors, while THC does. CB2 agonism is responsible for effects on immune system, inflammation via autoimmune responses and inflammation in the GI tract associated with IBS, Crohn's and UC.


I’m curious of your thoughts of marijuana outside of medical value? I notice many people seem to only focus on the medical benefits and not the recreational benefits. Or the creativity and new spark or insight that marijuana or other psychedelics can provide. To me they all seem to be valuable tools to both the healthy and unhealthy mind. (I’m not assuming that you are against recreational use btw!)


I'm an advocate of recreational use. While I believe THC has potential for habituation, the type of addiction it induces is not at all comparable to addictions to substances like nicotine, alcohol, opioids or even caffeine. The habituation potential it has is on par with other psychological addictions, and is unlike addictions to substances that have strong physical components. I believe that marijuana substitution has potential for those who are addicted to stronger drugs when it comes to getting through withdrawals, controlling cravings and maintaining abstinence.

I can attest to the productivity and creativity benefits marijuana provides, and looking at well-known and successful creatives, many of them attribute some of that productivity and creativity to marijuana consumption.


Thanks for the reply. I agree with your assessment.


In the case of pain treatment, it seems likely that the psychoactive affects of THC may be a large contributor to its effectiveness. In that it distracts you from the pain.

And there are a lot of people who are going to be more comfortable taking a plant in its natural state, than using an isolated compound that's been through a processing plant they have no control over, and which depends on a regulatory structure they have no faith in to tell them its safe (and what they are expecting).

Basically, there are a lot of people very skeptical of the corporate drug system (for good reasons, frankly), and the availability of natural herbal medicines does (for the most part [aside 1.]) no harm to them, and actually can do quite a bit of good.

If they don't trust aspirin, then let them use willow bark.

1. Obviously there are exceptions to this. There are some herbs that are considerably more dangerous and harmful than the useful compounds isolated from them. But there are also many herbs that are perfectly safe to use, and still effective to one degree or another. In some cases, they are every bit as effective, and even safer, than the isolated, concentrated alternatives (see St John's Wort).


I would argue that if they don't trust aspirin, they should buy a kit that lets them make aspirin (or salicin, rather) at home from willow bark. Still safer than consuming arbitrary unknown amounts of salicin, together with whatever else is in the bark besides salicin.

Let me put it this way: the big-pharma drug manufacturing (and more generally, medical-equipment manufacturing) pipeline is set up such that the only thing about a drug that should be able to kill someone, is if the drug's active ingredient itself has a bad interaction with their body.

Something like medical marijuana, meanwhile, can kill you by heavy-metal soil toxicity; by pesticides; by coincidental allergens in non-active-ingredient plant matter; etc.

None of these things will be checked for when you get a dose of medical marijuana.

An analogy: would you trust IV saline solution that's just salt that someone poured into "carefully collected rainwater" and then put into a bag? Even for an immunocompromised patient (i.e. exactly the kind who consumes medical marijuana for e.g. supportive cancer treatment)?

No; you'd distill the water, wash and recrystallize the salt, and basically do everything else you can to ensure that "salt and water" is all that's in the "bag of salt and water" you're putting into the patient's bloodstream. Because that's how you ensure that some random variable doesn't creep in and mysteriously make them sick in a way that's impossible to diagnose.


IV Saline Solution is not a good analogy, that's a very different case from herbal medicine.

People have been using willow bark for pain relief for hundreds if not thousands of years. They have not been injecting saline solution.

There's reason to believe that, in some cases, it is better to get medicines in their tried and true forms (those used for hundreds or thousands of years) rather than their more recent isolated forms (which only have a few decades of use). There could be beneficial interactions between all those unknown substances. In some cases - again see St John's Wort - the natural herbs are more effective, safer, and with fewer side effects than the concentrated drugs. And they are infinitely more available, since they can be grown right in your back yard.

There are of course exceptions to this - there was the very popular Chinese herb that had been used for a thousand years that turned out to give you throat cancer.

Don't get me wrong, I use the medical system. I also sometimes use herbal medicine, but I'm much, much more likely to reach for Advil than I am for willow bark. But I understand those who reach for willow bark, and recognize the validity of their reasoning.

Personally, I want to see these herbs tested in proper trials so we can determine which are pure placebo, which are effective the way St John's Wort is, and which are dangerous the way that Chinese herb was. If we can identify the ones that are actually effective, then that opens up a ton of room for people to self medicate and frees up resources in the medical system for those who really need them.


The thing is, unless you operate in a system that also has a pipeline for manufacturing and delivering medical marijuana to pharmacies—and the patient is likely to take advantage of that, rather than just using their medical-marijuana card to go to their local head shop—then you as a doctor have a choice to make, between "prescribe them something they can only [in this country] get at a pharmacy, which is therefore likely to be okay", and "prescribe them something they will get wherever the market allows, and thus is of whatever quality the market will bear."

It's the "whatever quality the market will bear" part that I worry about.

Consider: if you buy a bottle of ground willow-bark sitting on a store shelf in a random bodega... where did it come from? Who made it? Where did they grow it? What are the legal requirements re: pesticides, soil toxicity, etc. in the country they grew it [since it probably wasn't here]? And how certain are you of those answers?

And mind you, Chinese herbs are a bit better, even, since they're mostly just considered "food" by standards bodies, and so it's pretty hard to import them (or even derivatives of them) and local growers get regulated for "food purity" by entities like the FDA. (No standards body can protect you from things that inherently contain compounds nobody is aware they inherently contain, of course. Unless some other compound in the herb was considered the active ingredient, and isolated out...)

But, well, let me put it like this: my local pharmacy has some homeopathic tinctures (for some reason. At least they're on the bottom shelf out of most people's sight.) Who made those? And, given that they started as poisons before being diluted, how sure are you that they actually "did homeopathy correctly" and diluted them so that they're not actually going to poison you? DIY, then? How sure are you that you can "do homeopathy correctly", instead of accidentally poisoning yourself because you didn't stir your cyanide tincture well-enough? And then, how confident would you be that some big-pharma company could—if they wished—do homeopathy correctly? I'm guessing a lot more than your confidence in either BestElsewhere Imports Co or in your own two hands.

That's what I'm getting at. It's not about what happens when you grow it yourself. It's about the worst quality of product the market could potentially deliver to you when you go looking, and what that means for a doctor considering which delivery-vehicle to prescribe.


You're not wrong that herbal supplements are completely unregulated, and I totally agree that its a huge problem. But I still think you're putting far too much faith into the regulation we do have for the drug market. The regulatory agencies have been pretty thoroughly captured by the drug makers. And profit is a hugely corrupting influence. Just look at the insanity that has taken place with the makers of opioids and the opioid epidemic.

I think the point is that we need to work to improve the regulation of both concentrated drugs and of herbal supplements.

And in the mean time, if people want to use that plant because it makes the feel better - let them. And if their doctor thinks that plant will serve them better than the mass produced drug, let the doctor proscribe the plant. After all, their doctor is the real expert here.


> heavy-metal soil toxicity; by pesticides; by coincidental allergens in non-active-ingredient plant matter

The exact same risks are in your grocery store produce aisle.

I'll grant that illegal marijuana has higher risk, but if it's regulated like any legal food crop I don't see the difference; in fact, I'd say there's less, since people consume it in relatively low quantities.


...which is precisely why hospital food is just as processed as drugs are, to remove those variables.

Doctors know there's a certain number of X-factors a patient can't avoid (like e.g. eating food from random sources if they're not under in-patient care) but they don't want to introduce new ones if they can help it.

Another analogy: a doctor will never prescribe you "a supplement." They might tell you getting more vitamin B in your diet would be good, but they'll never tell you to go out and buy a vitamin-B complex supplement. If they think you really need vitamin-B in a pill, they'll prescribe an actual big-pharma-pipeline-produced pill containing vitamin B.

Why? Because who-the-heck knows what's in the random supplement you bought off Amazon is why. If the pharmacy says they got a pill from big-pharma mfgr X, and mfgr X says they produced it (and the FDA endorses mfgr X), then that's a chain of custody and a chain of responsibility that holds them to account, and so ensures that there really is vitamin B (and nothing else) in the pill. That means you're not getting any extra risks just from taking the pills, beyond some weird interaction between you and vitamin B. Whereas, those supplement pills from Amazon? Nobody checked those. Your doctor does not want you to take random unchecked pills that may or may not contain vitamin B, and may-or-may-not contain lead/mercury/cyanide/whatever. They want you to take pills that certainly do contain vitamin B, and certainly don't contain those other things. Thus, prescriptions; thus, pharmacies; thus, the FDA itself.


> Another analogy: a doctor will never prescribe you "a supplement." They might tell you getting more vitamin B in your diet would be good, but they'll never tell you to go out and buy a vitamin-B complex supplement. If they think you really need vitamin-B in a pill, they'll prescribe an actual big-pharma-pipeline-produced pill containing vitamin B.

You've seen very different doctors than I when it comes to calcium/D- and B- vitamins/multivitamins. They'll usually tell you "go get this over the counter." Sometimes with guidelines like "but not one of the ones with iron" or such.

Or even if they prescribe it, the pharmacy that gets the prescription (or maybe your insurance company - I forget which exactly had the problem with it when this happened to me) might say "just go grab one of the over the counter vitamins."


Hospital food is not "just as processed as drugs are." They give you cooked and raw fruits and veggies, not pills derived from them. The lettuce in your hospital salad is the same as any other lettuce.


>Let me put it this way: the big-pharma drug manufacturing (and more generally, medical-equipment manufacturing) pipeline is set up such that the only thing about a drug that should be able to kill someone, is if the drug's active ingredient itself has a bad interaction with their body.

"Should be" is a giant risk factor... "Don't worry Mrs. Jones, this drug shouldn't be able to kill you unless you have a terrible allergic reaction!"

Big-pharma has shown, repeatedly, that their sole motivation is not altruistic treatments of human aliments... it is that of any other corporate entity. Profit. I don't think that is inherently evil either.

Medical cannabis could kill you... you are right, but I would argue that you are much more likely to be killed from alcohol or tobacco related events.

For just one data point: I've worked in EMS for 14 years and I have never seen a cause of death that was directly the result of using cannabis. Unfortunately, I have lost track of how many people I have seen die that were the direct result of alcohol ingestion. Same for Oxycotin and other opioid based "medicine" prior to everyone and their brothers walking around with narcan.


Certainly, the creation of novel molecular compounds is risky, and you can only mitigate the risks you know about. But that's not the comparison we're talking about here. We're not talking about smoking marijuana plant-matter vs. taking new GSK LessCancerPainIum™️. We're talking about smoking marijuana plant-matter vs. taking a pill that was created by processing grown marijuana plant-matter, or with an active ingredient synthesized to be identical to the ingredient-under-test of marijuana plant-matter.

Personally, I've never heard of a case where Big Pharma has ever created a delivery vehicle for a well-known, Generally-Recognized-As-Safe active ingredient (like e.g. aspirin) that then kills, or even harms, people.

Like, the Tylenol murders? Those were big news. It'd be even bigger news if the manufacturer themselves were responsible instead of some random MITM. But there has never been that kind of big news. They don't screw up when making pills. Pills are pills. Novel active ingredients can kill you. But—presuming the active ingredient is safe—the pills themselves killing you? When has that ever happened?

> Unfortunately, I have lost track of how many people I have seen die that were the direct result of alcohol ingestion.

Well, yeah; people are consuming arbitrary amounts of alcohol. That's what's bad about recreational alcohol use.

Same goes for opioids, in a different sense; addiction drives you to consume arbitrary amounts of opioids. That's what's bad about drugs of abuse.

And yet, as an EMT, you still stick car-crash victims with fentanyl, no? Even though it's an opioid, and potentially a vector for chemical dependence. But you're not likely to kill them with it. Why? Because it's a measured dose.

----

Note that I'm not arguing that the active ingredients in medical cannabis could kill anyone. It's been pretty well shown that they don't really have an LD50.

It's not the active ingredients I'm worried about. It's the rest. It's the reason that hospitals don't get food for patients catered from arbitrary restaurants. You want to control all the variables you can. A CBD+THC tincture is going to have strictly fewer non-controlled variables than smoking the raw plant. A crystallized distillate suspended in a PEG gel pill is going to have fewer non-controlled variables still.

It's not about not-killing people. It's about treating people, successfully, with the highest ROI per treatment-hour possible and the least time spent flailing around trying to diagnose unknown brokenness while the patient continues to suffer.


Active ingredients in pharmaceuticals kill people all the time. I recommend looking up FDA black box warnings before taking any prescription. My doc prescribed something to me without knowing about a recent black box warning.

FDA does a lot of good, but the trials that bring a drug to market are not foolproof, and many doctors prescribe off label.

I would estimate that legally regulated cannabis's other ingredients are an order of magnitude or two less risky than taking any pharmaceutical that has come to market in the past 20 years.


> Something like medical marijuana, meanwhile, can kill you by heavy-metal soil toxicity; by pesticides; by coincidental allergens in non-active-ingredient plant matter; etc.

> None of these things will be checked for when you get a dose of medical marijuana.

Medical marijuana is grown in controlled environments by licensed medical growers, the products are tested for heavy metals and contaminants like mold, and are tested for levels of active ingredients.

Strains are grown for their medical benefits and standardized yield of constituent active ingredients, and for patients that need an absolutely standardized product, extracts and formulations are produced that meet those requirements.

No one is selling some crop that was grown in Mexico, someone's basement or downstream from an oil refinery.


Not that you're looking for anecdotes but I've noticed a broader spectrum of effect when THC is in the mix.

For point 2, I couldn't agree more. I think it's just an industry maturity thing. My wife is using it for appetite/anti-emetic effects and trying to 'dose' with dry herb or pen vaporizing is a joke, and most of the oils/edibles are administered in a way that has pretty gnarly taste/aftertaste that has been counter-productive for her. (I've started making my own tablets but it still feels like a crap shoot)


Hydroponic cannabis is grown in highly controlled environments and the dosage levels are tested to be within an acceptable range. There are also dozens (hundreds) of other cannabinoids found in marijuana which (may) have additional medical benefits.

>It's like prescribing willow bark for a headache when aspirin exists.

Willow bark contains salicin, not aspirin, while marijuana contains both THC and CBD. Willow bark also doesn't have the same blood-thinning effects of aspirin, which makes both viable pain relief choices for different populations.

This really just sounds like "plants bad; pills good!"


My point was more, "measurement good; eating psychoactive things off the ground bad."

The "key advancement of chemistry"—the thing that makes chemistry chemistry, rather than alchemy (and as it happens, the thing that differentiates baking from cooking) is being able to measure the reactants we put into a beaker, and clean the product of the reaction of any side-products, such that we can then crystallize/distill/etc. out the product alone, weigh it, and thereby determine the exact potency of product. Once we know that, we can then do all sorts of things: dilute it to a controlled strength; create delivery vehicles that deliver it at particular speeds; put it straight into the body in ways that would just kill you if you put into the body all the other stuff that you isolated the product out of; etc.

Anyone can do this. People make THC tinctures and essential-oils all the time, in their kitchens. It doesn't matter to me whether you do it or someone else does it for you; but it seems irresponsible to me to tell someone to go eat the non-processed version for medical effect.

> Hydroponic cannabis is grown in highly controlled environments and the dosage levels are tested to be within an acceptable range.

Sure, you can control everything about the production of the marijuana itself. But the key to medical treatment is the last mile, and specifically the ability to relate a patient's response over time to a dosing schedule/pharmacodynamic profile for the drug. If you prescribe someone "medical marijuana", without fixing down how they're going to take it, they could very well do anything from eating the whole batch at once, to vaping it every three minutes, to just doing hits off a bong whenever they feel pain. These are not the same thing, and medically they should be different prescriptions if the doctor has any hope of knowing whether the treatment is working.

Pills (or, really, anything more specific than "here's a plant, go to town") let a doctor say something more specific like "take one of these every two hours", and then from there know exactly how much of the active ingredient should be in the patient's bloodstream at any given time of the day, and so be able to measure effects (and side-effects!) against those that are normal, or abnormal, for that level of dose being in the patient's body for that period of time.


Pills let a doctor reasonably guess that that the prescription will have expected results. When you get to psychiatric medicine it is a well-funded and socially approved game of wheel of fortune, e.g., https://www.verywellmind.com/antipsychotic-medications-black...


> Hydroponic cannabis is grown in highly controlled environments and the dosage levels are tested to be within an acceptable range.

the cannabis testing industry is largely garbage.

the labs that are properly equipped to do the testing are either forbidden from doing it because they're DEA registered, or they make plenty of money without dealing with fly by night operations that can only pay in cash.


Huh. Strangely my state requires all cannabis products to be tested for CBC and THC and the products are labeled with percentages of each. Why do you think they are garbage?


DEA registration is the only way you can order reference standards for these particular scheduled compounds. the DEA is feds. they don't give a shit about the state laws, and don't permit registered labs to do testing for organizations that are state-legal and fed-illegal.

so the labs that can get reference standards aren't allowed to do the testing.

that doesn't mean there aren't labs that are doing taking samples and then sending reports back. it just means the reports are lies, and the information printed on the labels is meaningless.

your state can require things all day long, that doesn't mean anything productive is happening.


Do you have any actual evidence that the labels on my weed are wrong? I mean, you could be right, but do you have any evidence?


>Personally, I'm a skeptic that 1. CBD+THC offers any additional medical† benefits over CBD used alone;

Why?

>2. that it makes any medical sense to prescribe a (non-dose-controllable) plant over a pill,

Some medication, in pill form, is highly toxic.. see opiates which is a common alternative to thc for pain relief.

How did your comment reach the top?


> Why?

Because there are no studies proving it has any benefit? Because, from clinical anecdote (i.e. stories from my doctor friends) CBD alone seems to work perfectly as a treatment for every problem where "try medical marijuana" is the current line on the treatment flowchart?

I mean, admittedly, I'm not friends with every kind of doctor. I don't know whether THC has any added benefit in cancer treatment, for example. That's why I'm not denying the benefits of THC; I'm just skeptical of them. I'd like to see some supporting evidence!

> Some medication, in pill form, is highly toxic.. see opiates which is a common alternative to thc for pain relief.

Opiates in pills are no more or less toxic in pill form than in their "native" form (e.g. the opium poppy.) There are even animal nerve toxins that are classified as opiates. It is the molecule itself—and the dose—that makes something toxic, not the delivery mechanism.

The point of putting something in a pill—or even more simply, of extracting and distilling an active ingredient into an essence—is to make the dose measurable and to control for any unknown variables (the other stuff besides the active ingredient), so that dosing can be done precisely.

Without first isolating and measuring the active ingredient(s), there is no way to, for example, make "extended release" or "immediate relief" forms of medical marijuana, because you both don't know how much THC+CBD is entering your body, and (with edibles or anything besides smoking) don't even control how quickly your own metabolism takes up the active ingredient from the plant matter.


The point of 2 was that you could synthesize a drug starting from Marijuana instead of prescribing it directly. It wasn't about prescribing opioids instead of Marijuana.


For myself cannabis literally has the opposite effects -- increases inflammation and pain (I have chronic back pain). So I think it's right to be skeptical because the compounds themselves have extremely variable results.


This is very surprising to me -- have you done any research in to this? I would be interested to go down the rabbit hole but if you did some of the research already maybe we can be efficient humans :D


IME, weed is shit for headaches and great for arthritis or pain from working out. It also reduces the amount of opiates you need to take, post-surgery. That said, I feel better without it. To each their own.


There are other anti-nausea drugs lol.

Maybe it's useful if nothing else works but come on.


I'm very optimistic as well. My family has hard-to-treat depression and there's a lot of reason to be optimistic about psilocybin. Michael Pollan's "How to Change Your Mind" was a fantastic read.

It only makes me wonder what other possibilities have been out there but banned and therefore unavailable for study and experimentation. Luckily the days of censoring and hoarding information seem to be coming to an end.

Of course as a society we love the pendulum effect. We'll swing it too far and then it will come back the opposite way too far (so much for my optimism :-P)


From my experience it's incorrect to think of psilocybin as some magic pill that will magically make your depression go away.

I'm in the camp that depression is rarely just some "chemical imbalance" in the brain that you were unlucky to be born with, and yet that is how we currently think of it and treat it.

It's most often the case there is something in one's past, very often from one's childhood, that has been avoided, and creates a chronic sense of worry/anxiety/depression that lingers.

Psilocybin has the effect of ego death - it feels as though the subconscious hold you have on your brain that pushes down uncomfortable feelings or memories just goes away. This paired with therapy can be very powerful because you naturally become much more open to talk through distressing things that you otherwise normally numb over and helps you process past traumas much more efficiently.


Agreed. Imo, psilocybin won't just magically fix a chemical imbalance in your head. But it can open you up (for the duration of its effect) to some thoughts and ideas that could help you resolve your internal issues causing you depression, and those thoughts and realizations are what can help with getting rid of depression, as those realizations can stay with you even after the trip is over.

Which is somewhat similar to what i have read about the ketamine therapy, which essentially just makes certain areas of your brain more neuroplastic for a short duration, helping you get out of your routine thought patterns and help create new neural pathways and reshape the existing ones easier.

Note: I am not a brain researcher myself at all, so what I said could totally be just some pseudoscientific bs, but that's what I got after reading a bunch on both of the topic in a lot of places, including other HN threads. If you want to correct some misunderstandings in my post, please feel free to reply. I will be very happy to correct my misunderstandings.


yeah not sure why my comment was downvoted tbh. i guess there is a large segment of the population that thinks of illness as something that happens to them, and doesn't want to take responsibility in controlling or mitigating it without a so called magic pill.


> From my experience it's incorrect to think of psilocybin as some magic pill that will magically make your depression go away.

I don't think you are accusing me of saying that, but just to be clear I completely agree with this. Michael Pollan's book also doesn't paint it as a "magic pill." No doubt some people assume that, but I don't believe it exists.

I do wonder about the accuracy of Freudian ideas, such as something in ones childhood being the cause or at least playing a role. It's certainly possible. Being raised by depressed people sucks, and there's a lot of scars that probably contribute to why depression seems to be inherited.


Magic mushrooms were the first substance to make me feel like myself after years and years of deep depression.

But I didn't get quite the one hit, life changing state of mind that is often attributed to psychedelics.

One thing that I have read is that the whole life-changing thing requires a transcendental experience - and that participants who failed to reach that echelon didn't experience long term improvement.

I can't really comment on that - because I simply never reached that breakthrough dose.

The biggest issue for me is that magic mushrooms taste kinda bad - it's rather hard to eat enough of them.

Truffles on the other hand, are completely inoffensive - tasting (in some way) like a slightly off nut.

I could quite happily snack on a big-ass bowl of those things, and watch enthralled as the world turned weird.


"Magic mushrooms were the first substance to make me feel like myself after years and years of deep depression. But I didn't get quite the one hit, life changing state of mind that is often attributed to psychedelics."

Did you take them under the supervision of a trained psychedelic therapist, with the appropriate dose, with the right intention, in a therapeutic context, over multiple sessions, using a protocol designed for maximum therapeutic effect (which usually includes talk therapy both before and after the sessions)?

Having the right set and setting are both absolutely critical to get the most out of psychedelics.


They're not talking about multiple sessions, they're talking about people advocating psychodelics who often claim that magic mushrooms are a wonder drug that you take once and it completely changes your outlook on life.


There's no way to guarantee a powerful, life-changing experience. Some people do have one on their first try, some take more tries, others never do. All one can do is optimize the dose, set and setting to increase the odds that it'll happen.


I don't exactly reside in a jurisdiction where that's an option.


Back in the day we'd make a chocolate shake and blend 'em in.


Curious about the mind-changing aspect. Will these drugs transform my personality type, e.g. from INTJ to ESFP?


Sativa-dominant strains have psychedelic qualities, offering dramatic introspective, frame-shifting experience. It isn't as profound an experience as one from psilocybin, but that's not necessarily a bad thing. I've experienced realizations while under the influence of sativa dominant strains similar to, if not greater than, those uncovered during therapy with a psychologist. However, other times the re-framing of reality was simply fiction or not as epic as what it felt like while under the influence. Since the experience is so introspective for me, I partake in it sparingly, in the right settings where I can get the most medicinal value from it.


Throwaway because I don't like to tell people I smoke.

I must echo this entire post. I'm able to learn so much about myself when high. Far more personal than a therapist ever gets. I do introspection sessions after smoking. I smoke twice a week and do at most 5 hours of introspecting every week. This year I'm doing every other quarter.

After smoking I think about how to better myself and insights just flow in perhaps about 3 really good ones a session. And while yes about 10% of my insights are incorrect it's not a problem to write them all down in your phone and verify in a couple hours.

Doesn't seem like many people have similar experiences.


Try listening to cognitive behavior therapy audio books while under the influence. I can't go too far into a chapter without pausing and losing myself in contemplation. Listening while under the influence is a great way to trigger introspection.


Have any recommendations?


Agree with this 100%. I’ve practically quit drinking and replaced it with a casual, infrequent smoke/edible. I find it far more enjoyable and far more learning. It’s also nice to not take in 1000+ calories. :)


> I've always been on the skeptical side of medical marijuana usage in all but the most extreme cases

Really? A friend of mine had a similar experience to what @ergothus described in their comments. The friend had a biking accident and got stitches. To ease the pain the doctor prescribed Aadvil / Tylenol, but those drugs just caused diarrhea. So he tried edible marijuana[in a legal state] and it helped him a lot through a few weeks of painful recovery without any side effects.

I find miracle claims suspect as well, I don't think marijuana cures cancer.


Low hanging fruit here may be ayahuasca / ibogaine treatment for symptoms of withdrawal from chronic opioid abuse.

It sort of makes sense intuitively. If you you can just make it through the agony of junk sickness. You are in the clear. A 36-hour dose seems preternaturally suited.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773453/


There’s a great book by Michael Pollan, called “Change Your Mind”, I think, which talks a lot about the history of psychedelic research in the US. Great read.


This is a fantastic book. If anyone is interested in exploring the therapeutic uses of psilocybin in a safe, controlled setting, one of my best friends runs the Atman Retreat (recommended here by Pollan: https://michaelpollan.com/resources/psychedelics-resources/)

Edit to add link: https://atmanretreat.com/


This is sub-anecdotal, I know - but I recently after many years of "don't mess with my head" took mirtazapine for mild-depression/over-awareness-of-the-actual-state-of-the-world-around-me.

I feel better. Only noticeable effects were that I fell asleep much faster and woke up (refreshed) remembering all manner of weird clear dreams. Previously was one of those people who for the last decade couldn't recall a single dream (and had trouble nodding off). My random guess is that dreaming/tripping just loosens the mind up.. maybe like a deep tissue massage for the mind.. allowing things to mentally move about a bit and drop back into place (or mentally gives your mind a chance to beat the previous day into manageable lumps)


"I fell asleep much faster and woke up (refreshed) remembering all manner of weird clear dreams. Previously was one of those people who for the last decade couldn't recall a single dream (and had trouble nodding off)."

Just another anecdote, but I've found many techniques that have worked for me to greatly enhance my dream recall that don't require any drugs.

The first technique is just to get interested in dreams, read up about them, study techniques of dream recall, dream analysis, the science of sleep/dreams, etc.

The second is to have an intention to remember your dreams when you wake up, and consciously focus on that intention before you go to sleep.

Third, when going to sleep try to remember your day in reverse, from the moment you laid down in bed back through your day to when you got up that morning. The theory is that you're kind of priming your mind to think back to your dream when you wake.

Next, as soon as you wake up write even the smallest little thing that you remember about your dreams down on paper. Alternatively, you can record your dream in a voice recorder, which is what I do as I find it much faster and more convenient than writing.

Something else that I've noticed is that if I move my body when I wake, it can adversely affect dream recall, so I try to stay as still and as much as possible maintain the exact body position that I woke up in while I record the dream.

Also, when I have a really long dream to record, I found that I would often forget the end of dream while writing it down, as writing all the details down would take too long and by the time I got half-way through I'd forget. So I suggest writing down some key words and images first, and then go back and fill in the details afterwards. The words and images you've written down will help you remember.

Then, what's helped me is to go over my dreams and try to make sense of them, look for patterns in them, and try to see the connection between them and my waking life. I've found they have a lot of meaning and aren't just "random neuronal noise" that some people make them out to be.

Using these techniques and others, and just taking dreams seriously and being interested in them led me to go from remembering maybe one dream every three months to remembering three long dreams every night, and filled up hundreds of pages in my dream journal with records of dreams and dream analysis.

The downside is that doing this takes a lot of time, so I stopped after a while, and lost interest in dreams, and went back to very rarely remembering my dreams.


This sounds very identical to my process as well. I obsess about recalling as many of my dreams as I can when I wake up. I have a similar experience all the way down to trying to not move my body or so anything that can disrupt my dream recall, including avoiding actively thinking about my dream (similar to a meditative state).

The only difference is that I don’t record anything after. I find that just thinking about it a few times after I wake up is enough for my satisfaction. Dreams are very powerful tools for thought that I think society could benefit more from.


Here's what I've found useful in helping to remember dreams: Set an alarm to wake yourself 2-3 hours earlier than you normally do, then fall back to sleep. Upon waking at my usual hour I'm usually able to recall quite vividly whatever dream(s) I had over that 2-ish hour period.


This is NOT a trial that was designed to assess the safety of psilocybin. This was a trial meant to show that a particular dosage of psilocybin is /safe enough/ to pursue further research in that dose range.

This was a /phase one/ clinical trial.

Phase One: administer small doses under very close supervision in a tiny number of people to determine whether it's immediately dangerous, or safe enough /for further study/. They used 89 - initial randomization of 30 each to placebo, 10mg, and 25mg. That's a good number for a phase one trial. But when we look at the sort of things that start hurting people when released to market, they're the sort of adverse effects that go undetected in trials with thousands of participants, and would need an infeasible large trial (>10k patients) to detect.

This trial does not prove safety. This trial is meant to establish a dosing range that is /safe enough/ to participants to allow for further study. They found no "serious" adverse effects, in healthy volunteers - that is, not depressed patients. Can drugs like this have different effects in people w and without depression? Yes they most certainly can, in particular if those people are on concurrent medications (which they will be, since this is being developed for treatment-resistant depression).

“We wanted to look at the safety and tolerability profile of our psilocybin, and to look at the feasibility of a model where up to six one-to-one sessions are held at the same time." No they didn't /want/ to - they /had/ to. This is article is just a press release.

Phase 2 is generally a range of doses, within the range established in phase one, wherein we attempt to determine, to a rough level of accuracy, which doses show toxicity, which show therapeutic benefit, and at roughly what proportions. This phase is meant to determine what dose will be used in a phase 3 trial, if any dose exists with an appropriate proportion of therapeutic benefit to side effect.

Phase 3 - a dose (or couple of doses) of a drug in a regimen meant to reflect real-world proposed usage is distributed and compared against either a currently used drug or a placebo. Depending on how big an effect is expected, how common the disease, etc. we'd look at trials of hundreds to thousands of patients. This is the trial where we get a real sense of safety, side effect profiles, efficacy, etc. This is the make-or-break line for getting your drug to market.

Phase 4 "trial" - aftermarket surveillance. Goes on for years after a drug hits market, because there's no trial that comes to close to capturing the rare side effects that may be visible when applied to the general population.

This was, also, presented to a neuropsychopharm conference, not published data. Which is to say, they're ready to brag about it, but they're not ready to submit themselves to close scrutiny.


https://www.caymanchem.com/msdss/14041m.pdf

Acute toxicity level 4 for Oral ingestion

https://www.ilo.org/legacy/english/protection/safework/ghs/g...

Defines Toxicity level 4 as ~ 2000 to < 5000 mg/kg

The most potent strain of "magic mushrooms" are at most ~2% by weight(Psilocybe azurescens)[0]. So according to all the de facto standard literature, a potentially fatal dose of magic mushrooms is over 3 ounces of dried mushroom per kilogram of body weight. At 68 kg I would need to ingest over 5 kg to come up to the lower bound of the LD50.

No one without an axe to grind could realistically argue toxicity is a real valid concern.

[0]https://www.shroomery.org/8700/Psilocybe-azurescens-taxonomy...


Acute toxicity and LD50/fatal dosages are fine when you're worried about acute overdoses or unintentional ingestions.

Those are not the measures we are concerned with when we're talking about uncommon or rare effects (which, like the Vioxx deaths, had an incidence of one in /thousands/ at standard dosages), or effects that manifest with /chronic/ usage (e.g., over years of use, as is common with anti-depressant therapy).

What you're discussing is apples to oranges.


It's not about toxicity, but tolerability limits and side-effect profile.


It's worth noting that they were testing with 10mg and 25mg, which is equivalent to about 2g and 4.5g of dried mushrooms which are significant doses (e.g. far from microdosing). They reported no significant negative effects on cognitive and emotional functioning which is surprisingly positive for such an experience. Instead it is just the expected psychedelic experience.

As to safety, the LD50 of psilocybin is pretty well established at very high levels, with physical effects being unreported below that.


The press release noted no negative effects. The poster they presented to the neuropsychopharm folk the other night noted a few hundred, but none life-threatening.

Poster: https://compasspathways.com/wp-content/uploads/2019/12/poste...


Still big news that anyone is even doing phase 1 trials, since you wouldn't tend to bother if you didn't intend to follow up with further phases. I.e. "X is safe in a phase 1 trial" is never a useful terminal fact that you set out to prove and then, having proven it, do nothing more.


The vast majority of drugs don't make it through phase 3. Most will fail by the end of phase 2. If we trumpeted every time a prospective intervention underwent the earliest phases of study... well, I guess we'd have what we have had for years. Constant claims of miracle drugs on the way, with almost no subsequent impact on human lives.

If you find the endless hype a source of optimism and hope, then ... well, I guess I /am/ glad you have another source of optimism and hope. I don't share it, though.


Oh, to be clear, I'm not excited by the prospect of psilocybin making it all the way to FDA approval. What excites me is that this is more evidence of a pattern of change in what medical research is being conducted. There were many drugs that we were "leaving on the table" before, that we're actually bothering to look into now. Whether or not they turn out to work for anything, at least we'll know, instead of pretending they don't exist!


Thanks for this breakdown. Any thoughts on how this process might unfold for psilocybin as opposed to a drug that's subject to a chemical patent? Funding, timing, etc.


I'm not familiar with the company running this trial, but I can basically guarantee you they have found a way to patent this. Their intention is to come to market in 5 to 10 years, and there's no way they're bearing the expense of phase 3 trials just to become a generic manufacturer. Psilocybin isn't hard enough to manufacture (as opposed to say, propofol) to provide any sort of moat. They'll probably try to patent either an extended-release form or a particular administration device (e.g., inhaler).

E.g., the company that did the major trials for ketamine actually studied the s-enantiomer of ketamine using a nasal spray, which is quite distinct from the years of data we've accumulated on racemic ketamine with prolonged IV infusion. But this let them get a patentable version of ketamine on the market.


They can’t get a “composition of matter” patent, since psilocybin is already known.

They could get a “method of use” patent that describes treating a co diction with psilocybin.

Even without either of those, the FDA will give them 3 years of market exclusivity (no other drugs will be approved).


Are controlled experiments necessary for proving safety? Intuitively, there shouldn't be a placebo effect, and you could get twice as powerful a study by giving twice as many people the drug and using statistics for the general population as the control group.


No. For phase 1, it's generally sufficient to show that few or no people had life-threatening adverse effects, that none of the life threatening effects were plausibly related to the drug, and there were no meaningful hiccups in CNS, pulmonary, or cardiac function.

In this case, they went for a placebo set-up because they were also trying to grab a little data to show whether 25 mg was significantly distinct from 10mg. The comparison to placebo was not needed, but is winning them a little extra publicity.


What is general population? I guess the study exclude people with more than 95 year old and people with terminal cancer. Other exclusion factors are not so clear, so you need to know the results of no treatment in the same population. For this, you need to split the group at random.

Note also that the study probably include some regular visits to the hospital. Some people may eat more healthy food a few days before a blood exam so the doctor gets happier. Some people may change other habits, like no binge drinking. So you need to measure the results in a group that follow the same explicit and implicit rules.

Does the report of the symptoms use the same criteria in the study than in general population? What about dizziness? Does this produce dizziness? Does the general population report dizziness to their family doctor? Replace dizziness with chest pain, or constipation, or whatever symptom you are interested.

Also, people lie to their doctor because they try to be nice. It's not a voluntary lie, but if there is a study about curing something, people want to be nice and give optimistic feedback. You must have a double blind control group so you can compensate this.


Why shouldn't there be a placebo effect? It's well documented for basically any drug, even for alcohol. Serve people non-alcoholic drinks but tell them otherwise, and they get drunk.


Because the trial wasn't about finding the expected effect (drunkenness) but the secondary effects. People don't get heart disease or cirrhosis from non-alcoholic drinks, or at least, I'd be interested in reading the study where they do.


No, but they can get short-term secondary effects such as nausea, headaches the next day, etc. Probably this category of things is what they want to control for.


Related: How To Change Your Mind is worth reading. It covers the history of psilocybin & LSD research including the early parts of this recent resurgence in interest.


I was performing my own informal tests on various psychoactive agents in the late 60's and early 70's and can attest to the efficacy of psilocybin, as best as I can remember...


Some charts and data:

https://compasspathways.com/wp-content/uploads/2019/12/poste...

"Psilocybin administration to healthy participants: safety and feasibility in a placebo-controlled study"

"Poster presented at the 58th Annual Meeting of The American College of Neuropsychopharmacology, Orlando, FL, USA, 8–11 December 2019"



I'm gonna sound really cliched but I have become really fascinated with Psychedelics thanks to the Joe Rogan podcast.

I wouldn't say I am depressed but as someone who doesn't drink, smoke, drugs or take caffeine. I really want to try them.

The fact that mushrooms have been used by shamans all around the world since neolithic times, is truly fascinating.

I hope to try them at some point although at the moment I have been trying Sensory Deprivation Tanks and it really has reset my mind and emotions.


I’d steer you toward kava kava as a legal and otc way to change your mind and emotions for the better or more open. Also St. John’s wort.


I would add in the non essential amino acid L-Theanine [1]. Has a nice calming and focusing effect.

[1] - https://examine.com/supplements/theanine/


I get that from matcha in the morning. Very focused, almost driven sort of energy. Definitely a nootropic for my purposes.


Personally I didn't notice any difference before or after or during going through a bottle of it.


I am not a neurologist nor a doctor and I am entirely guessing, so I should not even comment, but some people may not be affected by small amounts of amino acids like this depending on their diet, gaba receptors, existing amino acid intake such as already drinking green tea or using arginine or citruline, or other medications. It is entirely possible that your α waves are already elevated from something else or that this amino acid isn't metabolized correctly.


kava is okay as a replacement for a muscle relaxer or alcohol if you want to drink dirt that makes you pee like a race horse, but, I wouldn’t put it anywhere in the same league therapeutically as psychedelics.


After googling, it appears that kava causes liver damage, thanks but no thanks


Yes you probably would not want to take it for an extended period of time [1] There is not a direct causation link to liver damage as of yet. It may be that people have a preexisting issue that is exacerbated by kava.

[1] - https://examine.com/supplements/kava/


There was something of a hit campaign against it at one point. I forget the specifics, but it’s safe if you do your homework and buy from proven sources.


That's happened to several food compounds. Scientists don't spend time on a compound unless there is a compelling medical need to do the research. There just isn't much money in supplements / foods as compared to prescription drugs and the risk of litigation is really high, according to a few of my favorite scientists that I follow.


1 minute on Wikipedia told me it is only the root which is edible, the rest is extremely toxic and causes liver damage.


Deeper googling might lead you to the conclusion that it’s totally safe. Anyway it’s not a psychedelic.


What source would you recommend? I've tried some name-brand kava tea and it didn't seem to do much.


Avoid any product called "kava tea". It's not tea and can't be drunk like tea. Kavalactones aren't water soluble so simply steeping a teabag filled with powdered kava root in water won't do anything.

Head over to /r/kava and the read the FAQ in the sidebar which includes a list of recommended vendors (and which ones to avoid).


If you want to get high, by the bulk kava powder from Amazon, but it tastes absolutely terrible.

For day to day use try the Yogi Tea with kava in it. It has cardamom so actually tastes good. The dose is very low so you’d need 3+ teabags to feel anything.


I’ve had extracts that didn’t do much. Pills of the powder have helped. The biggest experience I had was with the full on blending of the powder in a blender following a YouTube recipe video-wakacon from amazon.


Recently tried shrooms for the first time and was a bit underwhelmed, but not sure if I'm micro-dosing or what. Tried the regular variety and some other allegedly Thai shrooms, which definitely had a stronger effect. I tried a few stems at first, and then ramped up the dosage with slightly more 'visuals', but it's like I have to eat a whole handful or just let my body learn to process it or something.


From what I've heard (no real scientific data to back this) the stems contain very little psylocibin.

And the dosage for mushrooms is surprisingly high. For run of the mill strains, I believe 3.5 grams is considered a standard dose. Which is still not a blast you off the planet amount, but enough to experience visual distortions and euphoria.


On some strains 3.5 grams is a serious therapeutic dose requiring a sitter.

My last trip was about this much with another 1.5 set aside but I was blasted out of time and space and opted not to re-up.

It all depends on the strain.


The stems are the most potent part of the specimen. The caps have less psylocibin than the stems. If you bruise the fresh (and sometimes dry) specimen, you can see it turn blue. That indicates the presence of psylocibin. The smaller the specimens, the more psylocibin per gram you will have in a dose as there is significant psylocibin even in tiny specimens, including ones that have barely formed caps.


Typically you have to eat a whole bunch if your goal is to trip. Since they don't taste very good, people often eat them with other fun to help mask the taste (pickles, peanut butter, etc).

I'm sure you can find dosage guides online easily enough.


Right, that's probably it then. Yeah a concentrated edible would be interesting.


Majority of my mental energy in relation to drugs, some consideration:

- having a mortgage and life insurance attached to it

- parents prevented contact with their children due to government intervention

- people in jail for possession of drugs

- safe driving limits

- undoing 50+ years of propaganda and social conditioning


Awesome! Can't wait until 2030 when it is legal in a handful of states in the US.


Denver is actually full of those little chocolates wrapped in tin foil , easy to find easy to get and also cannot get arrested for as long as no $ exchanged per the new law that was voted by the people


It will be Denver first again


One day we'll be able to buy Psilocybin supplements on the shelves of stores like CBD, 5-HTP, and St. Johns Wort today.

In small doses it's super useful and seems to be relatively benign.


Always safe. Only it can’t be patented is why you never got it!


This could dramatically improve my family’s life.

Been following and supporting the research at Johns Hopkins since Tim Ferris brought attention to it.


I'm curious what the sample size is in this study?


6th paragraph

> ... 89 healthy volunteers.


Sorry, I was tongue-in-cheekly referring to @coffeemug's study.


You're fine, I just wanted to be helpful :)


How the hell do I get into one of these trials?


I got in to one of those trials when someone posted the sign up link on HackerNews and I applied. If you're near Baltimore you could see if you are a match for any of their current studies: https://hopkinspsychedelic.org/

Other in process research studies: https://maps.org/other-psychedelic-research/211-psilocybin-r...


The study seems to be this one:

https://doi.org/10.3389/fphar.2017.00974

Would it kill the PopSci article to include the DOI to the actual study?


Possibly of interest to others

> Post capsule ingestion, patients lay with eyes closed and listened to music pre-selected by the research team (Kaelen et al., 2017) (https://www.mixcloud.com/MendelKa/playlists/psilocybin-v13/).


A more relevant poster from last month: http://www.compasspathways-posters.com/ACNP2019_Rucker_poste... I don't think these results are published in a paper yet.


OK, we've changed to that from https://www.independent.co.uk/news/health/magic-mushroom-dep.... Thanks!


That's the wrong study.


Urgh. Thanks. We'll switch back to the original URL.


That's not the correct study. That one is from 2017 and published in 2018. The newest one used 89 patients.


Don't rush out and take mushrooms. If you're not taking it in a clinical setting, you're doing it wrong.


> If you're not taking it in a clinical setting, you're doing it wrong.

I'd be interested to see some support for this statement.


IMO There is a much better case for: if you're not taking it in a spiritual setting you're doing it wrong.

Anecdotally I've had the bad experience and the life-changing transcendent experience, all self-directed.

In my experience. It's not good for partying, but it's very good for meditating and inquiring deep into the nature of your being, what reality is, what Love is and what God is.

I've had long periods in my life of being a hard-line rationalist atheist. And I've had direct encounters with God. If there is one thing I learned it's this: You can't take anything as a belief you have to validate it in your direct experience.


if you take mushrooms you will abandon the simplistic view implied by your statement.




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