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Psilocybin repairs 'brains cells damaged by depression' in mice: study (leafie.co.uk)
403 points by pmoriarty on July 7, 2021 | hide | past | favorite | 328 comments

Psilocybin's effect can be amazing, but there were moments when I took truffles in Amsterdam that almost made me commit suicide. The sane part -- whatever was left of it -- recognized it and found an immediate way to stop it. So what actually happened is that I locked myself up in an empty room and cried (I couldn't harm myself there, because I didn't know how to get out until I sobered up a bit).

After one hour of crying I started noticing the magical effects of "we're all connected" etc. So after the bad part of my trip, the amazing things came. I don't mind that I cried, but I do mind that I was acting on a suicidal tendency that I never experienced sober.

I think I overdosed on it, being quite an inexperienced user. Because the first time I took half a dose, that was an amazing experience and it allowed me to reconnect to true child-like wonder (measured in units of whatever the smart shops in Amsterdam sell).

N = 1, I know.

All I'm saying is: be careful, have a trip sitter and a good set and setting. Don't go all out simply because you see a few positive papers.

I hope that nobody reading this has an unsupervised psilocybin experience in 2021. We are so close to being able to pay for a professionally supervised experience (and you can almost surely find one today if you look in the right circles and come with the right intentions) - these will enhance the moments of clarity and alleviate a lot of the confusion and darkness that are part of the territory with psychedelic experience.

I've benefitted greatly from a handful of psilocybin experiences in my life. The experiences were marked by long periods of profound terror and deep sadness, but I consider these to be powerful literalizations of anxieties, fears and attachments that helped me grapple with them in new ways. That said, I've glanced at scary thoughts that don't occur to me in daily life and came close to getting in trouble when I ran outside. Get a good babysitter - even better, track down a professional.

There are absolutely no guarantees with mushrooms, regardless of set, setting, sitters, professionals or not. To say nothing about the persistent hallucinatory disorder you are risking ever time you imbibe.

Even McKenna swore off mushrooms after he went through a hellishly intense existential nightmare. His brother wrote a book about it: The brotherhood of the screaming abyss. It’s not all rainbows and happy elves, there are trips so devastatingly dark that make death seem like a merciful release.

This is what worries me: I feel that the only reason that public opinion on psilocybin is recovering is because the drug is outlawed, so only the most motivated and prepared people would be willing to seek it out, and thus there is overreporting on the positive, life-changing effects that are impossible to be had without the drug. If the drug becomes more widespread, stories of "average people" taking the drug and experiencing negative effects could surface, causing mainstream public backlash, because there are so many more people taking the drug, some without the level of preparedness of the people willing to go off the beaten path (breaking the law, finding a distributor and a trusted copilot, being in a positive state of mind), so there are so many more chances that something could go wrong.

If psilocybin is legalized I feel that the responsible thing to do is to restrict its usage to the context of therapy. I have a feeling that this kind of legalization shouldn't be equivalent to marijuana where you'd be able to walk into a store and purchase some out of curiosity.

I haven't tried psilocybin yet, because of my impressions above, and because without knowing someone who could act as a guide I don't think it would be worth it.

"If psilocybin is legalized I feel that the responsible thing to do is to restrict its usage to the context of therapy."

What are you going to do with those people who choose to use psychedelics for religious or other purposes outside of a therapeutic context? Throw them in jail? We know that doesn't work, is counterproductive, and ruins lives. People are going to do them regardless, especially as more and more people wake up to how beneficial they can be.

If there's a media backlash from the inevitable increase in negative reactions as more and more people use psychedelics, we'll have to take on that backlash head on. Hopefully the world will react more sanely than the last time there was a moral panic about psychedelics in the 1960's and 70's.

We've learned a lot since then, there's a lot more information in the public about these substances, and they're not as closely associated with the counterculture, the antiwar movement, and antiestablishment sentiment this time around. They're actually much more mainstream now, and as allies there are many suffering people and even veterans who see the healing potential of these substances, so it's much harder to demonize their users as mere druggies and freaks, as was done in the 1960's and 70's.

As every successive year of the Psychedelic Renaissance passes and more and more positive results come out of all the research that's going on in to them, I'm feeling more and more hopefull that they'll fully become part of the mainstream culture in some fashion (starting with therapeutic and religious use), and that there'll be no major backlash.

> and you can almost surely find one today if you look in the right circles and come with the right intentions

It would be great to know more about how to make this happen

Tripping alone can be wonderful, just don’t take too much.

Don't come to Amsterdam and take drugs without knowing how to deal with it, please. This kind of stupidity is exactly what got psilocybin mushrooms banned here.

I'm Dutch and I live there (born and raised, I've seen way too many examples how drugs can screw people over because of being raised in Amsterdam). Nevertheless, it doesn't matter whether I live there or not. Experimenting with psilocybin is not easy, even when you're experienced with weed and alcohol.

Here was my thought process:

First time: I did half, that went amazingly well

Second time: I did a full dose, and I had the suicidal bad trip experience

Third time: full dose, got into a bad trip state again (just bad trip). I recognized the experience and knew what would happen, how to deal with it. It was completely fine. It was a wonderful experience.

Fourth time: potential explosive dangerous situation with the other person who used it (also did it 4 times, 4th time together with me as well). Crisis averted, having a tripsitter in this case (like in the second case) was an absolute must.

These experiences has happened in a span of 3 years, spread out quite evenly. I took it because of the research on psilocybin.

Truffles has been my first psychedelic. Ultimately, for me it has had positive effects.

It is what it is. Be careful, have a tripsitter. Not having a tripsitter was the biggest mistake I've made.

For other folx reading this, if you're keen on trying this, try to get ahold of 4-HO-DMT instead - it is an identical experience to psilocybin (psilocybin converts to 4-HO-DMT in your body, which causes its effects), but can be dosed exactly to the milligram, greatly reducing your chances of accidentally taking too much.

Also prevents the stomach pains of digesting lots of dry fibrous mushrooms. For the same reason, the experience with 4-HO-DMT can be shorter/quicker than with mushrooms but not by much.

I’ve found the following to be key in a good experience:

1. Do not take too much. This cannot be overstated. You don’t need to take 4 tabs of LSD, you don’t need to take a 1/4 oz of shrooms. Take the right, safe amount. Usually 1 tab or a 1/16th oz will do for me. Double that if I’m feeling up to it. I’m a larger person too.

2. Set/setting. Are you emotionally and physically prepared to go on a trip that could get _very_ complicated? Lots of people think they are when they're not.

Trip sitters can be helpful, but they do not guarantee a good trip by any means. Sometimes a person being around you that isn’t on the same plane of existence can make a situation needlessly uncomfortable. I’ve had a moment where we had to ask a trip sitter to leave mid-trip when things went sour. Once he left, we felt we could deal with things more naturally.

If it’s one of your first few times, a trip sitter could be great. Make sure it’s someone everyone in the group deeply trusts and likes. I’ve found I have better experiences without them personally.

> Not having a tripsitter was the biggest mistake I've made.


The problem is that if a person wants to learn how to deal with it legally, they have no other possibility than to come to a place like Amsterdam.

Wouldn't the solution rather be for Amsterdam to create a "newbie coffee shops" or something similar?

1. Create safe newbie-friendly places that provide an opportunity to safely experience a legal drug X.

2. Mandate that for a foreigner to buy a legal drug X, they must have an ID-like document that says they are experienced with X.

3. Once a tourist experiences X in a newbie-friendly place, they award him/her with an ID-like document that enables the tourist to buy X on their own.

Surely that create more jobs and opportunities in Amsterdam than the "bug off!" rhetoric I've seen from the local Amsterdam government.

To be clear, the staff in coffee shops do ask you if it's your first time and give you guidelines for how to use them safely, and usually informative leaflets are attached. At least in tourist places.

I was actually really impressed with the effort to educate people about truffles last time I went.

I've heard from friends that this exactly happens with DMT experiences. I'm not sure if DMT is legal here (they make it themselves, the ingredients are legal). Yet, they somehow advertize it publicly (?).

He did it in the south of The Netherlands.

"This kind of stupidity is exactly what got psilocybin mushrooms banned here."

Then why didn't alcohol, which causes way more problems than mushrooms, also get banned?

Downvoters and skeptics: You do realize that alcohol is involved in countless suicides, homicides, and other violence (not to mention the ravages of alcoholism), don't you?

It's the worst substance of the two, by far.

Amsterdam is one of the drinking capitals of Europe. Way more touists come to Amsterdam to get drunk than ever have to eat mushrooms, and they've always caused way more problems. But alcohol will never be banned there. Why the double standard?

Because there are some big money interests that don't want alcohol regulated (much) or banned.

There was an interesting study released in 2010 which attempted to measure the total cost, beyond just health harm, of different drugs. https://www.ias.org.uk/uploads/pdf/News%20stories/dnutt-lanc...

The UK government did not like that study, because it showed that many illegal drugs were ultimately much less overall harm to society (the direct users as well as those around them and the healthcare system) than alcohol.

Did the study take into account the prevalence of each substance? Alcohol would be the most prevalent by a wide margin. If it's normalized for prevalence however, then the results are mighty interesting.

Yes, it was normalized. It was a very comprehensive, well thought out study. Of course the researchers could still get the results they wanted by choosing which metrics to include in the comparisons, but the choices attempted to balance individual cost (physical, mental) with social (family suffering, divorce) and societal (burden on society from underperforming people, shared health costs, etc.)

The takeway was that alcohol was one of the worst, along with crack cocaine and heroin; ecstacy was really not bad, and weed was a bit worse but still nowhere near as overall costly/damaging as alcohol.

Century ago United States tried to ban alcohol, and it simply didn't work - it is way too easy to produce it from innocent food products. Exotic mushrooms or artificial drugs are much easier to ban.

Mushrooms is one of the easiest drugs to procure.

Some species like Psilocybe semilanceata grow in the wild, both in Europe and North America. You can just pick them if you know the type of habbitats to look for.

You can buy grow kits semi-legally (grey area, might vary on where you live) and you don't need any extra equipment. You get a plastic box and you literally just add water.

If you want to save money, you can buy only the spores. Then you just need some substrate which you can buy either at garden supply store or at a supermarket. Biggest issue is ensuring sterility, so a pressure cooker is recommended, but there are ways around that.

I'd say it's easier to grow shrooms at home than it is to make alcohol. You don't need any specific equiment like a still for distilled drinks, and you don't need any trial and error like you do when making fermented drinks. I know you could make alcohol without any equipment, but the end result will probably be quite poor. Meanwhile the shrooms grown without any equipment will be the same as any.

"Exotic mushrooms or artificial drugs are much easier to ban."

You can ban them, but your ban won't be any more effective than the ban on alcohol.

It's easy to get pretty much any drug you want.. especially in Amsterdam.

All the ban does is moves the market underground, gets organized crime involved, makes it much harder for users to tell they're getting what they paid for (possibly leading to all sorts of adverse effects like overdoses), and ruins people's lives when they're thrown in jail.

We know drug bans don't work and are counterproductive.

It's sad to see the Netherlands buy in to anti-drug hysteria after being one of the leading lights in constructive drug policy and harm-reduction for so long.

Exactly this. What happens south of US border is absolutely the same as the effect of 1920s prohibition. Communism and prohibition both looks good and neither works.

How, exactly, is the average person supposed to do them, then? It isn't like most countries let you walk into a shop and buy them. Realistically, it is the only way many people will ever get to do them legally. And realistically, if you are wanting to do psychedelics, you might not even find the same sort (I've generally found more opportunities to do LSD than truffles or mushrooms, for example).

Your words are kind of like telling young folks not to go and buy alcohol without knowing how to deal with it. The only way to learn is to take them.

"It isn't like most countries let you walk into a shop and buy them."

No. But you can walk in to the forest and pick them.

You really do need to identify them properly, though, and not just pick random mushrooms.

For help in doing that I can highly recommend Alan Rockefeller's excellent videos on psilocybin mushroom identification: [1] [2]

Another option is getting mushroom spores (which are legal in most states in the US) and growing them yourself.[3][4]

There are also various other legal psychedelics, like morning glory seeds[5], hawaiian baby woodrose seeds, and salvia divinorum[6].

Some sorts of breathwork (like holotropic breathing) is actually effective at inducing altered states of consciousness comparable for some people to psychedelics. It's not clear how safe such breathwork is long-term, as not enough serious studies of it has been done, but at least breathing is perfectly legal everywhere.. last I checked.

[1] - https://www.youtube.com/watch?v=pInqVRRva7M

[2] - https://www.youtube.com/watch?v=VcL-7u80kjs

[3] - https://old.reddit.com/r/unclebens/

[4] - https://www.youtube.com/watch?v=f0gJTeTT-pE

[5] - https://erowid.org/plants/morning_glory/morning_glory.shtml

[6] - https://erowid.org/plants/salvia/salvia.shtml

"No. But you can walk in to the forest and pick them." If you live by such forests. I happen to now (and do), but I haven't always had such a luxury.

And again, lots of folks don't have the luxury of growing. Just because there are other "legal" options doesn't mean much: These are going to act differently than what you get in Amsterdam.

I have no doubt that breathwork can make altered states, but I very highly doubt it is comparable to drugs. And again, this isn't really going to prepare you for, say, truffles in Amsterdam. If you don't like breathwork, you can just stop and do something else. If you don't like where you are at on drugs, you just have to wait.

"I have no doubt that breathwork can make altered states, but I very highly doubt it is comparable to drugs."

I was super skeptical myself.. so much so that even though I'd heard of holotropic breathwork at least a couple of decades ago I didn't bother to try it because it just sounded like complete bullshit.

But I did eventually try it, about a year ago, and I was amazed that it did in fact induce a state that was comparable to at least a low dose of psychedelics. Some people have reported even more powerful effects.

I aborted my self-experimentation out of concern that it might cause long-term health effects (as, paradoxically, hyperventilation -- which is what holotorpic breathwork mostly consists of -- can cause oxygen deprivation to the brain) but at least now, one year later, I haven't experienced any adverse health effects that I can detect, so might give it another try.

The really long-term effects (like 10 or 20 years later) are still unknown, though, as there just haven't been any serious long-term studies of it.

Another interesting possibility (which is again, mostly unstudied by science yet) is combining breathwork with other means of inducing altered states of consciousness.

Just like any other even remotely dangerous activity, having someone trusted with experience is the best way. Otherwise start very low and wade in. I would ABSOLUTELY tell young folks to not just go buy alcohol without knowing somewhat how to deal with it. Alcohol at least has enough cultural guard rails that a kid will generally know that drinking an entire liter is a bad idea.

So I’ve been this idiot.

Drugs aren’t really my thing, I’m more of a beer guy, but the first time I was in Amsterdam I experimented with edibles.

The first couple of times was just kind of nice, chilled me out, had a good vibe etc.

Then I got some from a different shop, and it was a nightmare! Headaches, heart racing, hallucinations, and it hurt to open my eyes. I thought my heart was going to explode.

To make matters worse I was sharing a tiny Air BnB (one room basically) with two other friends and there was nowhere to go, so I was just curled up in a ball tripping out while they drank and played cards, for hours!

Just horrendous lol, agree with the other commenters that there needs to be a safe way to try stuff like this out with people who know how to deal with somebody having a bad trip (as opposed to pointing and laughing, as my friends did).

"Then I got some from a different shop, and it was a nightmare! Headaches, heart racing, hallucinations, and it hurt to open my eyes. I thought my heart was going to explode."

You overdosed. Fortunately, the effect of overdosing on cannabis is purely psychological. You may feel miserable and be super paranoid, but there aren't any actual adverse physical effects.

Under such circumstances, if one is 100% sure only cannabis has been ingested and nothing else, and when there really are no adverse physical effects one could reassure the tripper that everything is going to be ok.

Hugs might be welcome, as might other physical contact like holding hands. Try changing the environment to somewhere more pleasant and more peaceful. Going out from a crowded party to peaceful nature might be a good idea. Changing music or putting on more pleasant music might help, as can looking at books of beautiful art or other fascinating images.

Something else that can be really good is having the tripper play a simple physical, acoustic instrument like a drum or a guitar, or to dance, chant or sing. This is an under-utilized and underappreciated technique that can dramatically change the mood as the tripper expresses themselves on a more primal level than speech.

Finally, in difficult trips (whether on cannabis or any other psychedelic) sometimes the best thing to do is not to try to run away but to go towards the difficulty and face it and try to learn from it. What exactly is it that you really fear? Why? Can you embrace it and surrender? Very often doing so will lead to a complete transformation of the experience from one of existential dread to bliss as one "dies" and is reborn.

I've just concluded it's more difficult to dose psilocybe truffles than mushrooms. The psilocybin content in the former is wildly inconsistent. I had two experiences, shared with a friend, spaced months apart using the same variety, vendor, dose (strong) and preparation method- The first was overwhelming and mystical, the second left us struggling to identify any effect beyond placebo. I spoke with the very friendly shopkeeper afterwards, also an avid psilocybe user, and she has also concluded sometimes they're just duds and prefers mushrooms for that reason. In your case, you got a scarier surprise as I guess you had the order reversed.

To respond to the somewhat rude "don't come to Amsterdam and do drugs if you don't know what you're doing" post:

You have a strong psychedelic substance being legally sold with totally unknown strenghth (as 'grams of truffles' doesn't count). What could go wrong? These products definitely need better labelling. I've also seen ridiculously strong pot edibles being sold in Amsterdam with insufficient labelling, but I digress.

This particular doseage mistake might not have been made if mushrooms were legally available as their psilocybin content is much more predictable. ("I did X grams last time and that was fine so I'll do X grams again!" is mostly reasonable) The problems are exacerbated by prohibition.

> I think I overdosed on it, being quite an inexperienced user. Because the first time I took half a dose, that was an amazing experience

Why did you go for a full dose when the half-dose was amazing? Did you expect a different outcome?

Every time I took truffles I had a 'dirtier' and less predictable experience, more often than not they were negative. At the time I was very experienced with wet and dry mushrooms so maybe it was a nocebo.

I have very unpleasant experiences on low doses. Maybe it is because the truffles are so weak.

What dose on that first experience?

Anyone know if dose needs to be scaled with body weight?

Dosage is usually measured in grams for the dried out mushrooms. There's no standard scale because the amount of psilocybin in each mushroom can vary quite a lot. Counter-intuitively, larger fruits tend to be less potent than smaller ones. The amount you take should depend on the kind of experience you want. Body weight shouldn't make a big difference. (These assume potent mushrooms such as Cubensis, Liberty Cap, Wavy Cap). Main effects kick in around 60-90 minutes after eating.

1/4-1/2g: microdose. You should still be able to function pretty normally on this.

1.0-1.5g: Recreational dose, lasting a couple of hours.

2.0-3.5g: Deep trip, lasting 3-6 hours.

4-5g+: Hero dose. Not recommended for beginners.

My first dose was 3.0g (cubensis) and it was great. I don't really see the point on microdosing and I see mushrooms as more medicine than a recreational drug. I usually take 3.5g as they're typically sold as 7g (1/4oz), which is 2 doses.

How often do you take them? I have access all the time (hopefully dried P. cubensis are not toxic after months in a vacuum container), but they're not addicting and I keep forgetting about them :) My first dose was 7g (was supposed to be 4, but my old kitchen scale didn't measure properly) and I can assure everyone curious that it's not fun, lol

Around 2 or 3 times a year. Not took any for 8 months. I also use DMT occasionally. Last time was about 6 months ago.

I've had 7g myself and yeah, I wouldn't recommend it. 3.5g is enough.

In my experience it is better to measure the number of shrooms you are taking as the max. dose per shroom is pretty consistent vs. measuring the total weight.

If only Psilocybin was available as a substance so we could just measure μg directly.

If you pick fresh this may be a good idea.

When you buy dried shrooms, it's not easy to tell what one fruit is because they shrivel up and break easily. Some sellers break them up deliberately - if some fruits are more potent than others, then by mixing them, the total psilocybin content is more likely to be similar in every package they sell.

Interestingly, some vendors sell "mushroom pills" and "mushroom chocolate bars," where they do this on a bigger scale - mill the mushrooms down into powder form and then thoroughly mix the powder to give an even distribution. The idea then is that each piece of chocolate in the bar contains the same amount of psilocybin - and with some trial and error taste testing, they can recommend how many pieces of chocolate to have for the desired effect. This also doesn't give you the same nausea you typically get by eating the dried mushrooms directly, which might give you a better trip.

The strain of mushroom taken can also greatly influence the experience. Some strains are far more potent than others.

First experience: half

Bad experience: a whole one

Smart shops in Amsterdam have a pretty standardized dose that they sell. I forgot the actual amount of grams.

This does not match my experience. I've found they have beginner, intermediate, or advanced truffles, presumably types with different natural dosages of psilocybin in the different types of Truffles. I've only taken the beginner ones and had a good time.

I think in both cases we took an intermediate one. But I don't fully remember tbh.

When I went, they had the doses already set out like beginner, intermediate, advanced. Whatever you took, they recommended taking half and then waiting about 30 minutes. If you felt ok, you could take the other half.

They should always recommend beginner, if you haven't had experience with truffles before.

Just google psilocybin dosage erowid...

Were you on any other drugs at the same time you took mushrooms?

Did you have a good set and setting when you took them?

Set and setting was neutral. I was curious that's all.

Back then I didn't mix drugs.

Now I sometimes mix alcohol with weed in certain social situations (don't do it, this is a personal failing on my side).

"Set and setting was neutral. I was curious that's all."

Your curiosity was part of your set (or mindset), but it's still not clear what the setting was (ie. where you did it).

On the subject of mindset only, it definitely helps to make it as positive as possible (same with setting too, by the way). A neutral mindset could easily get to a negative mindset once you start tripping.. it's harder for that to happen if you have a very positive mindset.

It's also good to have an experienced trip sitter you trust and like, to have constructive intentions for the trip, and to prepare in other ways (such as being in a comfortable, safe, and familiar environment at a time when you don't have any responsibilities to do anything else than enjoy yourself and don't have to deal with any people you aren't extremely comfortable around).

Some other things that can help a lot are to have a good playlist of music to listen to (see the Johns Hopkins Psilocybin playlist[1] for a good example).

Other props that have been successfully used to guide trips in a constructive direction were photographs of loved ones to look at during the trip, and a rose to look at towards the end of the trip.

The time you trip can also influence how it goes. Some people like to time it so that they get to see the sunrise towards the end. Others prefer to trip during the day. Tripping in nature can be very nice..

In modern therapeutic contexts, the trip is done in a comfortable apartment with pleasing decorations, with a mask you put over your eyes to shut out the light and headphones with a carefully curated playlist (so you can go deep inside), and a therapist at your side.

This is a far cry from how most people trip recreationally, where they might be in a party, club, or festival among people they don't know with music they can't control or just out in the streets. That can be a recipe for disaster.

[1] - https://www.hopkinsmedicine.org/news/articles/inside-the-joh...

So I have a family member that suffers from depression. At some point at a party we convinced her to drink some mushroom tea. She was amazingly together for 6 months after. Magic mushrooms should be legal.

For anyone else reading this and considering it -- you really need to be careful before recommending this for someone with depression. If they are not prepared for the experience it can be deeply destabilizing. Bad trips are real. Shroom tea is generally very strong too.

It absolutely can work for depression sometimes, just be careful and intentional, and don't just talk somebody into it who may not be ready for it.

A "microdose" is enough to alleviate symptoms of depression without risking one's psychological stability. There is really no need to take more than ~0.5 grams of cubensis unless the goal is deep insight/profound experience.

I completely disagree with the term "microdosing" though. I think this should be considered a standard dosage. Nobody calls a few ml's of cough syrup a "microdose" just because half a liter can cause euphoria, disorientation, etc. Calling this amount of mushroom a "microdose" only furthers the impression that psilocybin is a primarily recreational substance.

> A "microdose" is enough to alleviate symptoms of depression without risking one's psychological stability.

Not only the body weight of the person is going to matter, yields of active substance varies heavily and there is no consensus on what a microdose is. Cut-off can be as low as 0.2 grams.

Psychedelic use is correlated with an increase in neuroticism though, and not as a function of the badness of the trip. Plus in a susceptible person even 0.5g can trigger a first psychotic episode.

I find such claims of safety unfoundedly bold and honestly irresponsible.

One of the problems is that most people don't know they are susceptible and only find out after. It's a dice roll without some kind of ability to do a screening.

But no studies have proven so far that microdosing is even effective at all.

Are you under the impression that it isn't primarily a recreational substance?

If you plot out all usage globally, recreational use is probably going to be the most common case. However, being recreational is not a property of the substance itself, so the term you both were using is misleading in that sense.

Are you under the impression that a substances effects are somehow mediated by their legality?

Not at all. I just realize that these are primarily used for recreation. It could change - I mean, look at cocaine - and it can be both (opiates, for example).

Fair enough.

Cocaine is both too, by the way, stops intra-nasal bleeding post-op.

Completely agree that it's not for everyone, and that those that do try it should thoroughly (and I mean really thoroughly) educate themselves on what they're getting themselves in to and how to maximize their chances of having a good experience. For this I'd recommend "The Psychedelic Explorer's Guide"[1] by James Fadiman as a good start. Erowid[2] and PsychonautWiki[3] are good for experience reports and reference.

People with pre-existing health and psychiatric conditions, and young people should be doubly careful. The physical and sometimes psychological effects of some substances can be dangerous, especially when mixed with other drugs (alcohol is a particularly bad one to mix with).

Psilocybin mushrooms are some of the safest psychedelics around, but at the very least be absolutely sure you got the right kind (have them identified by experts or grow your own)... and starting with lower doses, in a good set and setting, with someone more experienced than you who you like and trust is prudent. Have some quiet days to integrate the experience afterwards, maybe with a therapist.

[1] - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut...

[2] - https://erowid.org

[3] - https://psychonautwiki.org/wiki/Main_Page

"People with pre-existing health and psychiatric conditions, and young people should be doubly careful. "

And since we are talking about "depressed" people, that should qualify as a preexisting psychiatric condition.

The problem is, in most places there are no professional therapists avaiable who can (legally) work with mushrooms. And really, long term depressed persons, often have no one around, they can prepare a trip with.

"in most places there are no professional therapists avaiable who can (legally) work with mushrooms."

Despite that, there are underground therapists who will do just that.. and even licensed therapists will sometimes do so. Discretely ask around and you might be pleasantly surprised.

"really, long term depressed persons, often have no one around, they can prepare a trip with."

There are free, online trip sitters that you can contact here:




The problem is, in most places there are no professional therapists avaiable who can (legally) work with mushrooms.

This is the real sadness to me. So many people seem to start dabbling in various forms of drugs as a way to ail their problems, and if there were qualified people who could help with that (beyond merely dishing out the typical SSRIs, benzos or stimulants) I think a lot of good could be done.

To be clear, this was well planned, in a safe environment, at dusk sitting on the back acre with family and friends and a small dose with constant communication.

These type of drugs have been shown time and time again to be massively effective in treating depression, anxiety and PTSD. It is a crime that ultra conservative socialty morals have prevented a more in depth study of their use. The fact of the matter is we treat our vets with a cocktail of drugs for PTSD that have major side effects and provide little relief. It was my experience and the experience of serval people I know that had PTSD that the use of magic mushrooms provided a substantial and sustained relief.

This is critical. You cant/shouldn't just go out on a whim and take shrooms. Either find someone who knows what they're doing and can walk you through it or do your own research and take it slow. Know how much your taking (as best you can) and don't over do it first time. Bad trips _suck_ and aren't going to help anyone.

Set and Setting folks.

They should probably be taking a sub-threshold dose anyways. The effects are the same and there's no risk of strong hallucinations.

thank you for posting this.

I think that there is always a survivorship bias with such anecdotes. We mostly hear about stories of people who have had good experiences with it - they share the recommendation to others too. On the other hand people who have had bad trips are less likely to talk about it.

To prove survivor-ship bias, you would have to show that somehow either bad or good experiences never gain visibility, which to me doesn't seem to be the case at all.

With natural medicine there's always people who point out the downsides, but with products made by the pharmacological industry, there's always those who defend SSRIs.

Is it even possible to gather some actual data on this issue without obvious bias either way?

The medical industry seems to have obvious motive to downplay any natural remedy as it doesn't make them money, and actively competes with their own products. On the other hand what motive would the average person have to unreasonably hype up things like the healing power of shrooms?

The medical industry has obvious motive to unreasonably hype up the healing power of shrooms, because they are illegal to distribute and use, and their dosage is uncertain. If they are judged effective, they will only be distributed by big pharma in specific, approved preparations and distillations.

> what motive would the average person have to unreasonably hype up things like the healing power of shrooms?

It's something to hang a personality from.

Big pharma is not going to be pushing for shrooms, LSD, etc. Many studies show these substances can have curative effects after a single use, which means no more money for them. Things like Ketamine that need to be taken more often are far more useful to big pharma, which is why that is being prescribed now IMO.

Big pharma is not the main driver of ketamine use for treating depression right now, as it's no longer patented so nearly as profitable for pharmaceutical companies. There is a newly patented ketamine derivative called esketamine that is making inroads in to depression treatment, but plain old ketamine is still used quite a lot.

There are a couple of drivers of ketamine's popularity for treating depression:

First, it actually seems to work astonishingly well for a lot of people (certainly way better than standard antidepressants), though not for everyone.

Second, it's a big money grab for ketamine "therapists" (I use "therapists" in quotes because many of them just sit around while you get your injection, and don't actually provide much if any therapy) who can charge $500 or more per treatment (which usually isn't covered by insurance), and people often come back for treatment multiple times a week or month for long periods of time. The cost of ketamine itself in these treatments is negligible.

An interesting development in ketamine therapy is the use of ketamine lozenges, which patients can take at home and therefore are way cheaper than having a medical team inject you with ketamine in their office.

>On the other hand what motive would the average person have to unreasonably hype up things like the healing power of shrooms?

Ego and I'm-better-and-more-enlightened-than-you attitude. You find this very often with cannabis smokers or "ents" as they fancy themselves. Also it's not that hard to find people peddling any type of dubious method : Homeopathy, crystals, acupuncture, Chakra meditation, putting up angel figurines. Often with the same amount of conviction and zealousness.

Read trip reports on Erowid.[1]

There are plenty of both good and bad trip reports.

The thing about bad trips, though, is that many people actually get a lot out of them, and find them to be therapeutic or something they learned from.

I've personally learned a lot more from my bad trips than my good trips, and ultimately found them a lot more rewarding. Not that I'd want to have a bad trip, but I found them to be a lot more insightful and those were the trips that really helped me grow, while the good trips were just fun.

[1] - https://erowid.org/experiences/

"On the other hand people who have had bad trips are less likely to talk about it."

Depends, it can also go the other way around.

I remember from my teenage years, that mostly the horror trips from some persons, with the scary anecdotes of people who stayed on the trip and never came of it and stayed in some asylum, were openly shared.

One of the reasons, I was very cautious and never did a mushroom trip at that time and especially not in a potential bad environments like parties, focused on drinking.

That was my experience as well. In my later teenage years there was a pretty successful movie around where the protagonist develops schizophrenia after using LSD one single time and his subsequential descent into "madness". That scared me off psychedelics for decades.

Sounds like "Das weiße Rauschen"? (The white noise, but I think he did mushrooms)

If so, I saw that one too ...

That's the one and you're right, according to wikipedia they were doing magic mushrooms not LSD.

Great and intense movie. So far the only time where I can say with certainty that a movie changed my life.

The thing is that even bad trips can be very, very useful if you treat psychedelics as a tool for exploration of your mind. I had two super bad trips - with 7g and 5g dose, in both I felt like I'm trapped in my mind and there were no world outside of my mind, and that idea was constantly repeating, with me feeling that there is no time and it will be forever like that - it was like pure hell :) Ultimately it was mind opening for me and I would recommend mushrooms to others if I knew that they are mentally strong and healthy.

That's because:

- bad trips are rare if your respect set and settings, which every responsible consumer will tell you to do.

- they have been used politically in bad faith. It's only fair to not add to the stack of propaganda.

- most of bad trips are not a bad thing. It can be spectacular, but rarely dangerous, and may actually be a good thing. My only bad trip helped me grow just like my good ones. It was not pleasant, just like throwing up stale food is not, but I was mentally healthier after it. Some dark things are inside of us all, and it's good they come out, but the experience is likely not something we crave for.

Talking about survivor bias, I meet a girl that tried magic mushrooms first time in a Saturday night. She was minor, young and naive at that time. Her night ended with a CPR.

She learned a valuable lesson that weekend about buying funny stuff in plastic bags from strangers.

Good for that person. But I'm not sure if that was "smart" to convince somebody with mental problems to drink mushroom tea at a party ... that's recipe for disaster.

Counterpoint, I took it one time and it set my mental health back 5 years. It took that long for me to wrap my head around what happened and get back to feeling secure.

I think we give magic mushrooms FDA approved based on your anecdote.

This isn't the first time I've heard this. There's plenty of other sources that seem to corroborate this anecdote; and let's all not forget. The plural of anecdote is evidence.

All that said, actually waiting for FDA approval does seem a lot less risky

Anecdotal: report of clinical experiences based on individual experience, rather than an organized investigation with standard research features, such as appropriate controls.


I think it's fair to say that medical research is not scaled up anecdotes.

The plural of anecdote should be hypothesis

>The plural of anecdote is evidence.

While I find the anecdotes compelling. I would assume that to make multiple anecdotes evidence you'd have to at least register these anecdotes systematically, otherwise you only hear the extreme ones that people like to tell.

Yeah, that's my bad. I meant to say data, not evidence. But you'll note that I didn't weight the quality of it. Anecdotes (plural) are data points, interpretation of them is left to whomever wants to use said data.

A temperature sensor that you know isn't desiged to work at subzero is reporting -30 consistently. It may be -40 or -20 but you know it's below zero.

Someone reporting symptom relief from depression, (which is something who's most severe symptoms are by definition subjective,) after taking psilocybin is a good data point. It without a doubt has helped.

Why, how, and discovery of caveats notwithstanding; it's something worthy of understanding, and with anecdotes (plural) consideration for use * . Just because the picture is incomplete, doesn't devalue the existing data points. Which is the thing I was trying to push back on. My data points may be weak, or noisy. But my data points are worth more than your scepticism. Full disclosure, I'm a card carrying sceptic saying that. I always think there's more to be understood, but merely devaluing the data points you currently have is not the way to go about it.

Ask questions, don't raise complaints.

* : some restrictions apply

dang - can we add "in mice" to the title?

Yup, always up for that. almost tempted to write some code to try automating it

I'm always impressed how quickly you respond to the bat-signal.

It's a sample-bias illusion, like the Super Bowl prediction scam.

Could you explain a bit more? Or point to a ressource / story? (Failed to find something relevant by searching!)

There's a classic scam where you send a letter correctly predicting the Super Bowl winner and then collect "investments" for your future predictions (i.e. scam people out of their money). The trick is just to mail out the same letter for every team.

I guess it's hard to google because anything involving "super bowl" is quite a haystack. But apparently it's called the "Perfect Prediction Scam": https://www.google.com/search?q=%22perfect+prediction+scam%2....

Apparently Alfred Hitchcock did a TV episode about it: "The Mail Order Prophet" (1957):



"I wish he hadn't done it. We have a very sensitive elevator man. He doesn't like it when he brings people up, and then they don't ride down again. It confuses him."

Given that he just expressed his affinity for writing code for things, I'd assume the bat-signal also sounds a buzzer in the HN-cave... ;)

i forgot what thread was that, but someone linked this twitter account lol


Haha first proper laugh of the day

What we need is some code to turn a human to a mouse.

Every study works in mice.

Human trials, not so much. Also, who would volunteer for depression + psychedelics before and after brain biopsies to prove this thesis? Maybe try it on the "before" sample in vitro first?

Of course it doesn't. The fact that we don't hear about all the trials that don't produce a significant result in mice is more to do with the state of science publication than to do with mice.

This seems like something that could be measured with at least one of the scanning techniques we already employ. It seems like an MRI could provide a rough result that could lead to further and more direct testing.

Gross structural scanning is essentially worthless when it comes to pathway functions.

got me cured. acted in 15 minutes. 4 years of pain gone.

i have no words to explain the relief.

I wish I had your experience.

During mine, I cried a lot, I texted my mum but I'm still inside the same hole that I was in before. Also some additional experiments with LSD (halfdose as well microdosing) didn't help with my depression.

Why psychedelics help some people and not others is one of the most interesting open research questions.

Still, there are ways that you can maximize your chances of getting therapeutic benefit out of psychedelics.

Doing psychedelics with a trained psychedelic therapist that you like, respect, and trust is probably the most effective way.

Something else you can do is read some good guides like James Fadiman's The Psychedelic Explorer's Guide[1] and the MAPS Treatment Guide for MDMA Assisted Psychotherapy[2]

[1] - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut...

[2] - https://maps.org/research-archive/mdma/MDMA-Assisted-Psychot...

it should be done with a therapist to get reliable results.

i'm a highly introspective person and worked 10% of the times for me.

so it worked for you when you finally did it with a therapist? or it worked 10% of all the time spent with a therapist?

no always in party context without therapist. happened by surprise actually.

What do you feel changed mentally? People have described it as mental knots being untangled. Would like to hear your feedback after the trip.

What dose? Just one trip?

1g mushrooms two weeks ago that did most of the job and 150ug lsd on sunday that did the rest .

in both cases i was in safe contexts, which is very important.

also in both cases there was an introspective phase at the end of the trip followed by a relief phase approx 15-30 long.

i'm so tempted.

it should be noted that this not recommended doing this out of a medical context.

> it should be noted that this not recommended doing this out of a medical context.

How could you even do that? As buying and possession of psychedelics is illegal in most countries.

There are both underground and licensed therapists who will work with patients who use psychedelics. Discretely ask around and you might find them.

Try asking around at psychedelic conferences and psychedelic meetups.

Also try contacting MAPS[1] and CIIS[2] (which has a training program for psychedelic therapists), and related organizations. Contacting people doing research in to psychedelics might also be fruitful.

[1] - https://maps.org/

[2] - https://www.ciis.edu/

The idea of a licensed therapist who does psychedelics is something of an oxymoron because even if they are licensed for doing therapy they aren't doing anything that they were taught to do in school so I don't see the point of looking for someone with a license.

You could just have a friend you trust babysit.

There are places which train licensed therapists to perform psychedelic therapy. Take a look at CIIS for one prestigious example: [1], [2]

More from MAPS: [3], [4]

Finally, laws around psychedelic use and therapy vary around the world. In some places in the world (like in parts of Europe and South and Central America) psychedelic therapy is much more widely practiced above-ground than it is in the US.

[1] - https://www.ciis.edu/research-centers/center-for-psychedelic...

[2] - https://www.ciis.edu/research-centers/center-for-psychedelic...

[3] - https://maps.org/news/media/8532-psychology-today-how-to-bec...

[4] - https://maps.org/training

It's been an established method of therapy for well over 40 years now. While it's not my personal preference to include them, there are certainly many experienced and licensed therapists that will conduct sessions with psychedelics.

I'm not saying there's anything wrong with this method of therapy but it reminds me of the time a relative went to a licensed therapist who did past life regression hypnotism. (And it's well documentation that there is something wrong with that!)

A licensed therapist who does psychedelics is someone outside the norms of society while at the same time carrying a license that carries the implicit promise of following society's rules. It just strikes me as "weird" to seek that out.

That's fair enough

it is illegal in mine, a single therapist has the authorizations to perform this therapy here in switzerland.

on the other hand it is perfectly legal for food/oil traders in geneva to starve entire countries / destroy an entire planet for short term profit.

i suspect psychedelics will remain illegal here for a long time since at least half of our politicians are paid by the pharmaceutical industry, so that would crunch a multi billion market.

Great! But to be clear, you are talking about diagnosed depression, right?

diagnosed burn out, but no diagnosed depression. i however feel the difference, even if i can't give scientifically relevant data.

You do not need a diagnosis to be depressed. What a counterintuitive logic.

that wasn't the logic -- parent never mentioned what they felt relief from.

for all we know it helped their rheumatoid arthritis.

Yeah, that was my point. And the word 'pain' actually reminded me of cluster headaches, which are treated with psilocybin exceptionally well. And yes, many people will experience long term changes without having suffered any illness (diagnosed or not). It's just that under the topic of this thread, well assume posts are about diagnosed depression.

You definitely need diagnosis to be called “clinically depressed”.

For all we know lay folk use the word depressed for feeling bummed. (Not insinuating this is the case with the GP)

agreed. i'm not claiming any scientific data here, just a personal experience.

however i wouldn't be surprised my dendritic tree grew 10% last two weeks like the article claim.

(I work in healthcare) There is something very odd or perhaps magical about these agents. I don’t really understand why they exist. What purpose do they serve to the mushroom? And how is it that similar agents exist in fungi, plants (ayehuasca) and amphibians (DMT from toad venom)? And also how do they produce such dramatic effects (generally beneficial when used judiciously) in humans with seemingly very little toxicity? There are basically no other molecules like this in the biosphere.

There are a lot of compounds that are poisonous to most species, but where some species have adapted defences against them, rendering them harmless. (IIRC capsaicin is like this in humans.)

There are also compounds that are toxic to basically every animal species for low-level common-animal-ancestor reasons, but which exist in the plants/fungi they exist in, in concentrations dictated by what’s required to kill/ward off the particular predators that plant/fungus had in its evolutionary environment. Aspirin, caffeine, nicotine, cocaine — these are all effective pesticides. They kill or severely harm insects. But we’re orders of magnitude larger than insects, so they have orders-of-magnitude less effect on us (unless we make orders-of-magnitude more concentrated doses of them, of course). That change in quantity, is reflected by a change in quality — i.e. having “a little bit” of caffeine does very different things to a body than having a lethal dose of caffeine.

Its also worth noting that often the experience of actually consuming these kinds of things, results in symptoms not that different from actual poisoning. Stomach cramps, nausea, the 'spins', double vision.

While there is plenty of anecdotal support for the longer term benefits of etheogens, the road to a better understanding of yourself and place in the universe is strewn with people hiding in their beds or under a table. The psychonaughts experience isn't exactly a piece of cake and shouldn't be taken lightly. Likewise, the 'why' of why these things help with issues like depression are obvious to any one who has taken the trip. These kinds of altered states force you to confront demons. They help you because they are >hard< and you have to deal with things. The experience helps with depression because it specifically brings to light the issues and causes of ones depression and you have to deal with them.

I'm concerned about the idea of boiling the positive benefits of something like mushrooms into a single compound.

My guess is that depression is basically caused by the feeling that "nothing changes therefore there is no reason to do anything, which means nothing changes...". But psychedelics are in essence a difference-experience, a changing experience. You are different after that. That proves to you that things do change, and also that there is love because we are all one.

But as earlier post pointed out, we don't really know why they do these things, why should they be so beneficial to us?. Let's say they are poison to thwart off plant-eaters. Then why do they work towards GOOD in small doses? Have humans evolved the capability for psychedelic experiences meaning experiences of unity which is a trait that helps survival of the specific species which experiences it?

The effect a natural deterrent causes in species that it didn't evolve to deter is pretty random. Even if the effect is positive sometimes, as long as its presence yields an overall fitness advantage (or at least no particular disadvantage), then evolution preserves it.

Like humans can be outright killed by touching some jellyfish, while turtles just eat them. I wonder if to turtles, jellyfish taste pleasurably spicy due to what chemical poisons us, like onions taste for us, which poisons insects. Overall, they're still good deals for the jellyfish and onions, since the traits are preserved.

> But as earlier post pointed out, we don't really know why they do these things, why should they be so beneficial to us?

Why does St. John’s Wort, passionflower etc have antidepressant effects? Why does penicillin mold produce an antibiotic? Why does gingerols act as anti-emetics? Why do coca leaves, coffee beans give a buzz?

There is nothing magical with an active compound to have a specific dose-response curve either.

> Why does St. John’s Wort, passionflower etc have antidepressant effects? Why does penicillin mold produce an antibiotic? Why does gingerols act as anti-emetics? Why do coca leaves, coffee beans give a buzz?

I don't know what listing a bunch of similar mysteries does to make the question less mysterious. Are you implying that these questions can't have answers and everything is unknowable? Is this one of the arguments where someone says that we can't answer your question until we answer every other question first? I don't get it.

The context of the thread is that somehow there is something romantically magical about mushrooms especially for humans. Me (and bunch of other people in the thread) throwing bunch of other compounds at it is to disprove that there is anything necessarily magical or secretly meaningful about them. It is mostly incidental or phenomena not specific to humans, therefore there is not much mysteriousness about it.

Not magical not romantic but yes mysterious. Or at least interesting.

The question is why do psychedelic drugs hit our brains in the peculiar way they do, which also has a therapeutic effect.

First why do they cause the experience that they do, and secondly why is that experience therapeutic? I think these are interesting questions without clear answers as of yet.

It has been speculated that mushrooms caused religion. Religion is spread all over the world so there must be something "fit" about it. It is as if mushrooms and human societies are in some kind of symbiotic relationship.

"Its also worth noting that often the experience of actually consuming these kinds of things, results in symptoms not that different from actual poisoning. Stomach cramps, nausea, the 'spins', double vision."

Those are the easier effects to explain. Much harder is why these compounds cure/treat depression or addiction, make people see infinite beauty or god, enhance their creativity, etc... Not much analogy to poison there.

I think that if I can make an animal who's trying to eat me hallucinate aliens on another plane, the animal kinda... totally forgets that it's trying to eat me.

Psychedelics in that sense may be distracting poisons rather than harmful poisons

It’s the opposite. The spores survive digestion and grow in the feces.

Maybe cows enjoy the experience and they help spread the spores.

Ha, much appreciate adding psychonaughts to my lexicon

Thanks for this insight. Searching it up there is evidence that psilocybin affects insect behaviour in a way that benefits the fungus that produces it [1]. This provides an explanation for how a neuro-modifying and low toxicity molecule could evolve.

Nevertheless, it still seems quite remarkable that such a molecule could coincidentally send a big mammal on a trip through the doors of perception.

[1] https://www.sciencedirect.com/science/article/pii/S175450481...

> Nevertheless, it still seems quite remarkable that such a molecule could coincidentally send a big mammal on a trip through the doors of perception.

Perhaps at first thought, yes, because mammals, insects and mushrooms are such different things.

To put it in perspective though, they share more than 2 billion years of evolutionary history when you look past their last common ancestor.

That M1 CPU in your new MacBook is a much mightier beast than the little black ICs in your grandfathers transistor radio, but they both rely on the same fundamental NPN silicone junction property. And that’s only 60 years of evolution.

> IIRC capsaicin is like this in humans.

Capsaicin triggers the heat-sensing nerves in mammals specifically. Scientists think this is because birds disperse the seeds well after consumption, while us mammals tend to crush the seeds with our grinding teeth. Peppers don't want to kill us, they just want to hurt as real bad ;)


it’s not really though. The mushrooms evolved independently a neurotransmitter that also just happens to work on humans. Fungi and humans have a common ancestor roughly 450 million years ago. It’s also possible that they evolved this by accident and the mushrooms that were mostly successful got carried away further and reproduced more because of this secondary utilization humans had for them.

Terrance McKenna entertained us with the theory that psilocybin catalyzed human language "on the mushroom dotted plains of Africa".




The “stoned ape” theory is one of the dumbest theories ever invented. I say that as a big McKenna fan - he’s a great orator and very insightful, but his theory is very transparently a way to elevate the perceived importance of shrooms. There’s a common trip motif that shrooms make one “more human” and the “theory” is just a projection of that.

Mechanistically it just doesn’t make any sense. The reason mushrooms make us trip is because there’s already a network there that they “talk” to (the 5ht_2a receptor system)

And how exactly would non-linguistic animals suddenly gain linguistic ability? They better hope everyone around them is tripping on the perfect dose too otherwise they’re just gonna perceive it as meaningless babblimg

> And how exactly would non-linguistic animals suddenly gain linguistic ability? They better hope everyone around them is tripping on the perfect dose too otherwise they’re just gonna perceive it as meaningless babblimg

I don't think this has to be an sudden event? Apes are already communicating with each other and have the relevant structures for communication in place. It isn't impossible for me to imagine that mushrooms with their creativity-heightening effects might offer insights to an ape on how to improve the utilization of that which is already there, making their communication more refined, precise and expressive. It also isn't impossible to imagine that in a group of social animals better communication would likely increase the probability of survival and leaving offspring, thus influencing evolution.

"The reason mushrooms make us trip is because there’s already a network there that they “talk” to (the 5ht_2a receptor system)"

But how does binding to the 5-HT[2A] receptor lead to, say, communing with one's dead mother, or to forgiveness of oneself or one's abusive father, or to a creative breakthrough on a problem you've been struggling with for months or years, or to an encounter with one's god, or to the realization that you/we are god, or to curing/treating depression or addiction, etc?

These are open questions that science doesn't have very satisfying answers to yet.

> These are open questions that science doesn't have very satisfying answers to yet.


It’s nowhere near complete but one place to start is psychedelic (a) increase communication across/between disparate brain regions, (b) synchronize the various waves of brain activity into a single vibration, and (c) reduces the threshold at which pattern matching / classifier networks will fire (thus the increased visual acuity at small doses and pareidolia and other visual effects at high doses)

I remember a study that explained (b), can’t remember anything else about it though :/

EDIT: https://ai.googleblog.com/2015/06/inceptionism-going-deeper-... is also great to think about. DeepDream produces very psychedelic images and the bit about reversing the network and having it recurse on pattern matching its on output to “massage” the raw input into alignment with a schema (akin to feeding output back into input) is very relevant

they sort of are open. your brain is basically a interpreting and predicting the world 24/7. it work by making meaning of what it perceives. a flood of a neurotransmitter basically alters the way the brain works and whatever experience you have is your brain trying to make senses of the new and unexpected electrochemical activity.

you are not communicating with your dead mother or you are not being a god.

it works for depression because it allows the brain to exercise and form neural pathways that are not normally allowed. even if we think about the brain as one organ, in reality there are a lot of interconnected neural nets that are regulated by a central supervisory net called the DMN. Under psychedelics, the DMN shuts down while the other networks increase activity.

I was careful to say "entertained", so I don't disagree with you, But just to engage further, what other satisfying models are there for non-linguistic animals suddenly gaining linguistic ability?

Evolution. Animals suddenly gain all sorts of competencies when the competitive pressure is on. Most animals already have linguistic ability, I don't think human language is all that special. We can do all sorts of fancy things with our brains that seem to defy explanation through the simple mechanics of evolution, but communicating the state of your brain to another of your species, that feels like basic stuff to me.

The Stoned Ape theory is a prime example of a phenomenon I've noticed where frequent users of psilocybin begin attributing all sorts of miracles to mushrooms. Everything becomes explained by mushrooms. I've seen it happen in person and online. It's a bit bizarre.

It's almost as if they were ingesting a substance which altered their thinking...

Look, I seriously love shrooms. I stopped everything else, especially weed with all of its subtly negative effects which creep up over time, and do frequent mushroom trips and occasional light dose of alcohol. That said, I find it funny when people do a drug that alters their thinking and perceptions on such a deep level but draw a line at where they think those effects begin and end as if the brain/mind was ever that clearly compartmentalized.

yup. The Stoned Ape theory.

Not just humans - animals may respond to these compounds as well. Like humans, or in a different way.

It is also possible that the answer lies somewhere in our evolution, not the mushroom's.

Couldn't you ask the same thing about aspirin or literally any other naturally occurring drug with few side effects?

> And also how do they produce such dramatic effects (generally beneficial when used judiciously) in humans with seemingly very little toxicity?

While toxicity may be low, it's very unlikely we'll find few side effects. The reason we don't know many ill effects of the drugs used in small doses is that we haven't studied them properly yet (meaning at a population level over time).

Isn't DMT biosynthesized endogenously in most mammals? https://pubmed.ncbi.nlm.nih.gov/31249368/

I think it would be fascinating to know more about the anabolic/metabolic pathways that create these molecules. Could it be we are seeing similar products created as mutations of core synthetic pathways?

The article you link to is about NN-DMT.

It's important to understand that the venom of Bufo alvarius (the Colorado River toad)[1] contains 5-MeO-DMT, not NN-DMT. It is NN-DMT that is colloquially known as "DMT", and the two substances should NOT be confused.

They are very different in effect, though closely related chemically.

5-MeO-DMT is widely considered to be by far the most powerful psychedelic on the planet. NN-DMT is considered to be much more powerful than traditional psychedelics like LSD and psilocybin, but still a pale shadow compared to 5-MeO-DMT. NN-DMT is a lot more visual than 5-MeO-DMT, while the latter is considered to be much more likely to lead to states of non-dual awareness and ego-death.

For more information on 5-MeO-DMT see: [2]

Something else to note about the bufo alvarius venom: these toads are under threat and might well go extinct because they're being recklessly exploited for their venom.[3]

Furthermore, their venom contains a lot of other compounds apart from 5-MeO-DMT, some of which are known to be toxic when ingested. So it should always be smoked, never ingested! Even when smoked the venom could cause health problems for people with heart conditions. The synthetic form of 5-MeO-DMT only consists of 5-MeO-DMT itself, so has none of these problems, though people with heart conditions should probably still avoid even the synthetic version.

Finally, some people who style themselves "DMT shamans" use very dangerous practices like pouring water in the mouths of people who are essentially unconscious under the influence of 5-MeO-DMT, mixing drugs, slapping and kicking people under the influence, and covering their mouth and nose... fatalities have resulted from these dangerous practices.[4] So if you are considering trying this substance very carefully vet who you do it with!

I strongly recommend reading and following the guidelines from The Conclave.[5]

[1] - https://en.wikipedia.org/wiki/Colorado_River_toad

[2] - https://psychonautwiki.org/wiki/5-meo-dmt

[3] - https://www.forbes.com/sites/davidcarpenter/2021/02/02/psych...

[4] - https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=86872

[5] - https://theconclave.info/

You don't think there's kin selection value in making any animal that eats you trip balls and/or freak out? In the wild I'd imagine any herbivore that spends six hours wandering around hallucinating and responding erratically if at all to outside stimuli will get eaten pretty quickly.

You have a point, obviously - but I wouldn't be surprised if mushrooms actually heighten awareness and response in animals and some people. Mushrooms tend to fog the mind only with regard to emotional responses. But other than that it seems one acts mostly pretty rational - only the perception seems to be changed. I took enough psilos and LSD to lose control of my ego and experience amnesia but from all I can say I never really acted irrational. Some tribes take psychedelics before hunting also.

I'm intrigued, are there any records of hallucinogens in recreational doses enhancing real world performance? In my own limited experience they can be fun, but not what you'd call practical.

How are you determining your own behaviour during your experience? Is it purely from your own recollections or is it from a third person viewpoint (video evidence, a sober trip sitter etc.)?

first of all it's a regular experience where somebody tripping is convinced s/he's acting weird just be assured that they seem completely inconspicuous for an observer.

If they are beneficial to us, and we grow the fungi, then it’s beneficial to them too.

We co-evolved with plants, many of the healthy chemical parts in plants were once evolved to be poisons or deterrents. Also the common biological base means that one plant creates dopamine and serotonin.

"What purpose do they serve to the mushroom? And how is it that similar agents exist in fungi, plants (ayehuasca) and amphibians (DMT from toad venom)? And also how do they produce such dramatic effects (generally beneficial when used judiciously) in humans with seemingly very little toxicity?"

These are some of the most important and fascinating open questions regarding these substances, the answers to which have the potential to revolutionize our understanding of the mind and mental health. Unfortunately, at the glacial pace that human studies in to psychedelics are proceeding[1], we will probably have to wait a very long time to find out.

Meanwhile, there are religious answers to these questions, as many psychedelic users consider these substances, plants, and animals sacred or even divine. Other theories, regarding psilocybin mushrooms, for instance, have been that they are some sort of alien beings who are trying to communicate vast amounts of information to humans or trying to influence human evolution. Similarly, I've heard theories that nature or "Mother Earth" is communicating through these substances, plants, and animals to humans to try to stop the environmental destruction they are causing, etc.

Materialists, physicalists, or naturalists[2] might scoff at such explanations (especially if they've never had strong psychedelic experiences, though sometimes even then), but I believe that it's likely that a great religious revival is heralded by the renewed interest and widespread use of psychedelics. Some have argued that psychedelics were the original cause of some if not all the great religions, and plenty of new religions are being inspired by psychedelic use all the time.. so such religious/non-materialistic/supernatural explanations and more are likely to become more and more widespread in the future.

[1] - While the popular view is that psychedelic research is running full steam ahead since we're in the so-called Psychedelic Renaissance, the unfortunate fact is that human studies of psychedelics are still very difficult and time-consuming to get approval for, and there really aren't that many.

[2] - https://plato.stanford.edu/entries/physicalism/ and https://plato.stanford.edu/entries/naturalism/

Materialists, physicalists, or naturalists[2] might scoff at such explanations (especially if they've never had strong psychedelic experiences, though sometimes even then), but I believe that it's likely that a great religious revival is heralded by the renewed interest and widespread use of psychedelics.

Is it not more likely that these substances just happen to match the knob labeled "profound" in our brains and crank it to 11? I hope these studies move very cautiously but optimistically, because as someone whose life was deeply damaged by a religious upbringing, the prospect of another psychedelic religious revival concerns me. Religion and mysticism tend to diverge over time, leading to conflict. Scientific knowledge tends to converge over time, suggesting science is a more reliable means of acquiring knowledge. So I hope a primarily scientific approach is taken with psychedelic research.

"Is it not more likely that these substances just happen to match the knob labeled "profound" in our brains and crank it to 11?"

Maybe. But regardless of what the more materialistically minded among us might think, many people are going to interpret these experiences religiously anyway. It's been that way all throughout history, and it's likely going to be many hundreds if not thousands of years until religious interpretations of experience dissappear.. if ever. (My bet is on never)

"I hope these studies move very cautiously but optimistically, because as someone whose life was deeply damaged by a religious upbringing, the prospect of another psychedelic religious revival concerns me."

Me too.. especially when these religions are full of people who have no compunctions on using violence and believe themselves to be the only possessors of The Truth.

Unfortunately, psychedelics don't automatically make their users in to tree-hugging, peace-loving hippies. See Charles Manson or Mike Tyson (sorry, don't mean to imply they're at all in the same category.. but they are both examples of heavy psychedelic users who aren't averse to violence... and Manson started a cult).

Some people are great at deluding themselves and others, and for certain types of people psychedelics can make such persuasion much more effective.

> Materialists, physicalists, or naturalists[2] might scoff at such explanations (especially if they've never had strong psychedelic experiences, though sometimes even then)

I've had strong psychedelic and dissociative experiences. There's nothing about those experiences that cannot be explained with materialism.

"There's nothing about those experiences that cannot be explained with materialism."

Or with religion. People pick and choose the explanations they like, and neither scientific nor religious explanations are going to be satisfactory for everyone.

It'd be another story if science could at least explain the really big open questions about the mind, consciousness, the mind-body connection, and how psychedelics work.. but we are very, very far from that.

Staunch materialist psychonaut here.

You're far from alone. There was an interesting thread on r/psychonauts recently about atheist psychonauts[1], and a lot of people identified as such.

Psychedelics clearly don't inevitably lead people to become believers... but still a lot of people do, especially when they have overwhelmingly powerful mystical experiences (which we know are pretty likely to happen on psychedelics).

[1] - https://old.reddit.com/r/Psychonaut/comments/oa6782/atheist_...

The most lasting message I got from my trips was "wow, we don't know shit. It sure is weird that we're all on this planet and don't really have any idea what's actually going on." No real insight into the nature of reality, except that it's pretty weird.

Well, Socrates' knowing that he knew nothing was counted a real insight! Uh, and his singular wisdom was proclaimed by a psychedelic-inhaling priestess in a temple, no less.

It didn't work for me though—in epistemology class once I said to the lecturer "I don't know anything!"—not being flippant, at the time I really felt I couldn't be 100% certain of anything—and he said instantly, unimpressed, "Don't you know your name?".. (Which didn't seem quite fair. He didn't "respond to the strongest plausible interpretation". Or maybe he did.)

The response to that is, yes but who is yesenadam?

The reasons are complicated and evolutionarily symbiotic.

Lure a "pollinator" to protect and spread it. Avocados were the diet of some unknown animal that no longer exists. Avocados shouldn't exist except for humans preserving and exploiting them.

Well, look at capsicum. Birds can't taste it but mammals can. Even so, most deer and some humans sure do like jalapeños.

Some compounds are deadly poisons to particular predators while merely annoyances to others. Beyond deadly poisons, there are deterrents like emetics, anticoagulants, dissociatives, and paralytics aimed at defending from particular predators.

These are evolutionarily-conserved because they add to the fitness of a species.

Nature is a hacker: it reuses (mutations) a lot of pathways and molecules for different purposes. We just hack compounds out of nature intended for other functions that also happen to serve our purposes at therapeutic doses.

Intelligent design.

A crazy idea: our brain is a fungi-like plant and even uses same chemicals in neurotransmitters.

We can dismiss this easily.

Fungi and plants were treated in the same category some thousand years ago, but times changed and now are categorized by biologists as new and very different creatures deserving its entire kingdom. The old concept of 'plants' has split into several unrelated lineages.

Fungi have a easily recognizable and unique cell structure than neither animals, nor plants have, so can't be the origin of our brains.

Fungi are the origins of all creatures on earth, humans included it seems. As far as I know, it's still the oldest identified complex organism on this planet.

> Fungi are the origins of all creatures on earth, humans included

Bacteria are older.

Nobody knows if that fossil is a fungus. It looks like one, but to me looks much more like a tiny sponge. I could be wrong and could be perfectly a third different thing. Ctenophora are now the oldest animals I think, so there was a lot of old complexity yet from the start that we don't know well.

I was thinking of Prototaxites which was maybe 470m years old (possibly) and humongous. Sounds like sponges are it (oldest) then. Until we learn otherwise.

I think my brain might be a truffle.

Another method which any able-bodied individual can try at home is multi day salt water fasting with multivitamin supplementation.

Elevated levels of autophagy after fasting result in the elimination of senescence-like neurons. Individual neurons of this type can negatively influence the extracellular environment and may promote induction of the same phenotype in surrounding cells, as well as driving aging and age-related diseases.

A quick google search seems to confirm that fasting can indeed help with depression:



Did multiple quite few 5 days fast, the max i got to was 10 days.

I experienced none of the effects. People claim to be sharper and more energised during fast, but all I experienced was noticeable sluggishness (no glucose, only fat as energy source) and bit more pissy about small things (though I recognise it and never act on it).

P.S. Worth mentioning, any water fast above 4 days can be potentially dangerous if you don't take supplements that regulate your bodily functions, like salt, potassium, magnesium etc. I have read accounts of people doing only water fast no supplements for 10-15 days and report serious symptoms of their body shutting down (maily cells dying due to lack of salt).

In my experience it is dangerous to go more than a day without electrolyte and multivitamin supplementation.

Care must be taken to avoid potassium overdose if supplementing with potassium. Sodium chloride is well tolerated on the order of no more than 20 grams per day spread out over the whole day.

If you can't go without multivitamin supplementation for a day then there's something medically wrong with your body.

Another potential positive benefit of fasting is it deprives the body of the energy/nutrients it needs to physiologically repress unexpressed emotions. Certainly if you have any past major traumas buried deep it may be beneficial to have someone well-fed along for the ride who can guide your thinking, but there's nothing quite like an extended fast to force you to jettison old cargo and take that ride on the emotional rollercoaster you've been avoidng for years.

> deprives the body of the energy/nutrients it needs to physiologically repress unexpressed emotions

Citation desperately needed.

What is the physiological mechanism through which we repress unexpressed emotions, and which nutrients does it consume?

As I began reading that comment I assumed it was a satirical response but it seems the user actually believes humans can “purge” emotions.

Not "purge" but rather "starve" or "transform" or even better "disrupt" standard chemical pathways. As many emotions depend on dopamine, serotonin, oxytocin and endorphins, starving/fasting kicks in the primary mode of operation and reduces disbalance caused by excess amount of nutrients... For instance there is a link between diabetes and depression https://archive.ph/f50wd


And as I read this comment, I'm amazed that this user doesn't believe calorie intake is a core component of emotional regulation and stress management. Has the user ever heard of terms like "stress eating" or that "hangry" has made it into the dictionary? Or has the user ever realized that despite all the stressors of Navy BUD/S and Army Ranger bootcamps, the one thing they do not restrict is calorie intake (and why)? Alas, poor skeptical user.

I believe they're criticizing the somewhat unfounded idea of a stress-induced uncovering of past traumas in order to purge emotions about said traumas.

It’s not about the content, it’s about the delivery. People need to be more respectful of others anecdotal experiences. Evidence based Science cannot read between the lines all the time

And they are all welcome to point at the chair and claim it won't hold any weight. But until they try sitting the fuck down their critique is irrelevant.

I posit that drinking a daily capful of bleach will purge you of past trauma and negative emotions. Your critique is irrelevant unless you try it.

Except I've already tried the thing I'm "positing", so it would only be right that you try your capful of bleach regimen first, report back to me with your positive results, and then I will gladly follow.

For anyone confused enough, bleach WILL kill you.

Yeah, I guess I should state the obvious punchline in case anyone is dumb enough to follow the fringe diet advice they read on HN: Drinking bleach will kill you and thus purge you of all past trauma and negative emotions.

People don't have to "believe" in it. If what you're saying is true so easily, then it should be very easy to form a trial that proves it.

Army Ranger School does restrict calorie intake.


Try a 72-hr fast sometime and you'll have your answers and more!

Ah yes, hunger induced delirium.

Nothing as special will happen after 72hrs of food fasting... humans can go on surprisingly long without food 8-42days and without food + water around 7 days.

Sure, you'll survive without lasting damage, but thinking such a fast itself won't impact your brain chemistry seems a bit much.

It will impact there is no doubt about it, but not in such dramatic way as 'hunger induced delirium' you need much longer fast than 72hrs (talking about food fasting, not sure about dry fast). 24hrs to 72hrs food fast is quite common as part of preparations for medical procedures as colonoscopy...


...and you know, also something humans routinely did for hundreds of thousands of years without ill effect (called winter time).



With the obligatory 'In Mice' addendum.

Also worth checking out in the context: https://peterattiamd.com/the-mouse-trap-lost-in-translation/


That sounds really interesting. Do you have any book recommendations that explain this process (ideally targeted at a non-medical audience)?

Dr Peter Attia is obsessed with the topic :)


Not a book but this does a good job exlaining it, https://youtu.be/FGoLcJxApCA

"the strong eat the weak", "autophagosomes are like soldiers", said my body builder standing in front of a "home farmstead" festooned set. .. this video is doing a lot more than explaining autophagy..

What it does for you is between you and your YouTube overlords.

For me, I try not to judge people for their body shape and listen to what they have to say regardless.

The "festooned set" is a common thing across YouTube influencers and affiliate marketers, this guy particularly likes to push bone broth and other keto related stuff. Doesn't mean he isn't damn well versed in the subject matter though.

If you like I can track down some old 3 hour long talks on autophagy and fasting if you'd prefer, those doc's are pretty funny too sometimes.

Sorry if my comment seemed negative about the guy. Sometimes videos that have very marked signs like this one tickle my semiotics senses. It's a highly appealing video and I just wanted to pause and think why, and what other things it was transmitting.

Not too negative, just wanted to make sure he was taken seriously, the amount of research and peer reviewed articles he covers in his videos is quite intensive, he doesn't half ass it at all.

I think 'The Cancer Code' by Dr. Jason Fung does a decent job of laying the groundwork.

That guy is a quack.

I mean, he's a licensed practicing physician in Toronto, Ontario and nothing he advocates seems too far out of the mainstream medical science to me.

Also, I just pulled out a copy of the book I mentioned, and in the appendix he's got 467 citations. I'd say ballpark over half of those are peer reviewed medical journals.

Doesn't seem very duck-like, but I'm interested to hear your take on why he's a quack.

Any able bodied individual with a decent understanding of microbiology can grow some mushrooms too.

In other words, Jilly Juice.

IME, there is always some nugget of truth behind bizarre public crazes.

You actually don't need the multivitamin. Salt is essential though. Magnesium and Potassium are also really good supplements to add.

But agree, fasting is great for cleaning up the biological cruft.

There's a free psych investor conference tomorrow (https://psych.global/agenda/) for people interested in what companies are working in the psychedelic space.

California just voted in favor of a bill that would allow those 21 and older to possess for personal use and social sharing LSD, mescaline and the psilocybin.

I suspect a lot of consolidation and new players entering, but it's definitely in its infancy and will be exciting to watch it mature. One company called Braxia Scientific is opening ketamine clinics throughout Canada and plans to do so in the US. They also just received funding from the Canadian government to study the effects so some of these companies are legit.


I'm kind of ambivalent about commercial interests entering the psychedelic space.

Hopefully some way will be found to keep the providers small, local, employee-owned, and ethical... maybe non-profit even.

Having experienced psilocybin a few times and agree it does have some of these positive, possible (but not guaranteed) effects, I also believe that similar effects are possible through entirely sober means, though harder to achieve for most people (proper meditation, talk therapy, certain relationships with natural surroundings).

A 10% increase in synaptic density and strength can be good or bad. Are these new connections rooted and grounded in useful things that pertain to reality, or are they connections rooted in halluconations? Or what?

Magnesium-L-Threonate (Magtein) also increases synaltic density but without hallucination. However it doesn't offer the serotonin effects of psilocybin.

Aerobic exercise regimens offer both, but without the hallucinogenic benefits of having a new perspective on things.

> The research found that the compound increases the density of dendritic spines, small protrusions found on nerve cells that aid in the transmission of information between neurons. Chronic stress and depression are known to reduce the number of these neuronal connections.

How well is the latter known? Is that consensus? Also, is it just an effect or a possible cause of depression? If it's just an effect, why would reparation be an effective treatment for depression?

I wrote a piece here about avoiding bad trips. Maybe it can be useful to someone. https://www.eleusiniaretreat.com/how-to-avoid-a-bad-trip/

In my opinion the main problem of the using of psilocybin, LSD and other psychedelics in medicine is unpredictable effect that depends on not only the status of a pacient but on entourage too. One time you have a good trip, but next time you get into TRUE HELL.

Recent research in to psychedelics has proven that we've learned how to control set and setting so that the overwhelming majority of people who do psychedelics with trained therapists have positive results.

Some people still have difficult experiences, but with the aid of properly trained therapists even those experiences can be constructive, and people can come out healed on the other side of even the worst trips.

I do not known such researches but I agree that it can work for some people, especially for suggestible people or who strongly trust in therapist. But in general we do not be able to control it. Any psy trip is similar to sailing in ocean.

It's not just about trust in the therapist. Music plays a huge role. In fact, I've recently heard a psychedelic researcher say that he now thinks of psychedelic therapy as a form of music therapy done with psychedelics.

It's also important to be in a safe, comfortable place, without people you don't intimately trust around, at a time when you can just focus on yourself on the day of the experience and ideally at least a day or two afterwards.

These are necessary but insufficient conditions. A bad trip may be triggered by a fleeting recollection/thought. I believe that a medical procedure cannot be based on such precarious approaches.

I haven't taken psychedelics in a therapeutic setting, but I have had a couple "PURE HELL" experiences, and those were still some of the most meaningful and instructive experiences I've ever had.

For anyone considering using psychedelics, consider that a "bad trip" might make you uncomfortable but it will also force you to confront your problems.

Would love to know the dosages they are using in the trials. Obviously, we're not talking McKenna level doses, but are we in milligrams or even as little as micrograms?

> we chose to use 1 mg/kg – the inflection point of the dose-dependence curve – to assess psilocybin’s effect on structural plasticity.


For psilocin, 25 milligrams is enough for many (or a good start...). Just like with THC though, it's tough to gauge how much is appropriate per person per experience per environment. A tenth of a gram may not be enough if you've previously consumed it the day(s) before.

Johns Hopkins uses pure psilocybin about the equivalent of 2.5 grams of dried mushrooms.

2.5 grams? That's enough for an exeperienced psychonaut to have a good time. That's way higher than what I would believe a therapy session would be going for, so I'm not buying these numbers one bit.

I would love to know, too! Oh. A search engine. What's this?

"Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo."

Is this the "new study" the article is referring to with "a single dose of psilocybin given to mice"? Oh. Some text. What's this?

> Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.

I'm not convinced these participants are mice.

(As an aside, I love the way they talk about double blind conditions as if you're not going to be able to tell whether that pill was 25mg of psilocybin.).

It's possible to have a blind participant if they've not had psilocybin before and they are going to receive either psilocybin or one of a multitude of other psychoactive substances (at least that's how Johns Hopkins did it).

You go to all the trouble to type up a smart ass response to show how smart you are with being able to use a search engine, yet you totally fail to provide the link which you found. This quote is meaningless without context of what study you found.

I'm pretty sure you can find the link using Google, also.

That is not the study referenced in the article. That's an older study.

You are right. That is not the same study. Thanks for pointing that out.

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