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Psychedelics Promote Structural and Functional Neural Plasticity (cell.com)
302 points by lainon 8 months ago | hide | past | web | favorite | 149 comments



I’m a huge proponent of safe psychedelic use, specifically LSD.

I was massively depressed and suicidal growing up (I had family problems, and two of my best friends killed them selves at 13 and 17).

I dropped out of high school.

I experimented with LSD and mushrooms around 17/18 years old.

And while I didn’t realize it then, my life massively changed for the better. Maybe I grew up. Maybe I took responsibility for my life. Or maybe... there was a synergistic effect that accompanied my psychedelic use. My religious family thinks it was all their prayer and god’s work... because it’s a miracle.

As I got older, the more I believe that it had a profound impact on my mind, and my ability to perceive the world and my sense of self differently, in an empowering way.

I now am an evangelist for psychedelic use. I share it with whomever I feel would benefit, educating them on the research, on the negative stigmas, and emphasizing how necessary it is to respect the substance and approach it with care and good intent.

I ended up attended a top 12 university. I worked hard.

Most of my friends at that university experimented with LSD. None of them are crazy. They all are doing amazing things. They’re all deep and insightful.

Psychedelics have gotten such a terrible reputation.

I believe it is immensely helpful for anxiety and depression.

I believe it needs to be adopted as a therapeutic alternative to current psychiatric therapies which are toxic and destructive and deadening by comparison. (I was on countless drugs growing up, dozens, prescribed by psychiatrists... they did nothing. Just made me more dead inside.)

I also believe psychedelics open the mind in ways that only radical life experiences can.

I think this mind expansion can be useful for learning, creating, and perceiving new ways of looking at the world.


> psychedelics open the mind in ways that only radical life experiences can

This is a good translation of the title of OP: neural plasticity is always active but never nearly as much as during major life events. Psychedlics are a shortcut to that sort of plasticity.


Quite the opposite. It stands to reason that the brain is much more vulnerable during episodes of high activity.

"open mind" is a hollow phrase, because you need an open mind to take the risk in the first place.

The only up side is that reason cannot overrule the nervous system at great length, which will sooner or later go into intoxication mode, and that the immune system can handle even chronic infections to some degree.

I would argue that some of the mental activity is caused by placebo effect, because I once experienced someone pranked, told to have been slipped MDMA, trying to embrace the situation and turning irrationally exited and happy for no substantial reason. Certainly some side effects may enhance the placebo effect, like weird after taste, alcohol or just staying up late and creating a suitable atmosphere, but believe is a strong cognitive bias. Otherwise one might just feel ill or poisoned.

A lot of the first experience involves sanity checks, so, if psychedelics have an effect on the currently running processes, so to speak, the ability to judge the situation will suffer first and inhibition won't kick in, or overreact. Then anything can happen with whatever one is liable to think about. Certainly nobody will dispute that normal productivity greatly suffers on a trip. So you can't really trust the self evaluation.


I believe it needs to be adopted as a therapeutic alternative to current psychiatric therapies which are toxic and destructive and deadening by comparison

There are people who have rosy anecdotes about each of the therapies you call toxic and destructive. There are also people with horror stories about LSD. You are inappropriately extrapolating your own personal experiences to everyone else.

It's ironic to say this to someone who's advocating mind expansion, but... you need to be a bit more open minded.


After extreme depression I lost some physical abilities, it came back but not 100%. It's most probably due to damages in my brain (hypoxia, inflamation, whatever). Anyway, since then I'm always wishing for some way to give my brain some fertilizer so I can get skills back. I learned music on my own, I acquired patience, dedication and sensitivity with it, but when your brain is cracked progress is almost inexistant.

Not long ago I found a shop that had CBD eliquids, they gave me a sample (3 strokes). A little bit after my brain was a minuscule amount lighter, but at layers that I never really had a control over (unlike the sensation I get when meditating, I can feel some parts of my brain going off). As usual, may be placebo, but still another thing that cause that itch for a little psychoactive help to regain my previous life quality.


You literally lose brain activity and effectively intelligence/IQ when you get PTSD. You can slowly train your brains with mindfulness, getting in the diffused mode of thinking. The trick is to focus on small victories. Learn different meditation techniques and try them out. You'll get your favourite ones eventually. FWIW, I can highly recommend going to a mindfulness course. Guided with audio, a decent book, and a (hopefully) good teacher you'll have use of it for the rest of your life. An unintended side consequence is that I am now, truly, never bored. I've been afraid to be bored without a mag, without my smartphone, without my bag with me, without my wallet, without my lock pick set, without electronic devices, without my powerball. Mindfulness skills I always have with me though (although I do mostly still prefer guided)


In my case it seems it was more due to cardiovascular problems than to PTSD or 'brain self-harm' if I may say so. But anyway, I do try to have deep slowing moment[1], aiming at stable relaxation. But I'm never sure what to expect from meditation. Give me your favorite books.

[1] a side effect of fubared cardiovascular system is that I had to monitor my breathing and heart a lot so I would naturally have sessions of calm slow breathing exercises.


Mind Illuminated by Culadasa has been recommended here before. It gives a path to advance and helped people with years of experience in meditation to become unstuck.


It's hard to describe, but I feel like I had a permanent "fog" in my brain. A lot of things just didn't click and I'd re-ask the same question countless times to confirm that I understood something.

Then, one day, I decided to try something and I felt like that fog lifted. That was about 5 years ago and things have been great ever since then.


So how do I get to experiment with this in a controlled and legal way these days?


You don’t.

But if you have the drive, and are willing to take a small risk, you venture into the dark web and locate one of the handful of chemists/dealers who provide the world with its supply and buy in bulk.

Or you find a friend who has already done this work.


To bad all the good Darknets were taken down and replaced with Honeypots.


Source?


Thank you for the info



This isn't legal or controlled, but if you spend some time attending music festivals, you can come across just about and drug you would imagine (speaking about the US). LSD and mushrooms are popular at these shows. Speaking from experience, I would that if you have a personality that can handle finding drugs, then this would be less risky than buying from an online source.


I am curious about that too.


Go to New Mexico for ayahuasca or peyote based religious ceremonies?



Oops


Well something like this may exist in New Mexico as well, just that's the one I know of.


step one is realizing that if you want to expand your mind you have to reject the systems of control that dictate to you which thoughts and behaviors are allowed.

put differently: the barriers to experimentation with psychedelics are the ones that you have constructed for yourself.


Look into 1-PLSD


What advices would you give yourself, if you tried it again in the present time ?

First time product, dosage, aquisition method and protocol ?

Anything to read or other things to know ?


Only do it with an experienced guide. Read Jim Fadiman's book. If you're serious, sincere, and patient you should be able to find a guide through your local yoga, meditation, new age, etc. scene. Michael Pollan's new book is excellent if you need a bit more motivation.

These medicines are far more powerful than you could possibly comprehend. Once you are in it, expect to have zero control, so you need a safe, experienced environment.


If you're going to take a psychedelic please read through the safety guides on https://tripsafe.org/ first. And like the other commenter noted, read Fadiman's book.

Also there are services that offer legal facilitated offerings: https://psychedelicsociety.org.uk/experience-retreats


The first time I tried it was with a musician buddy. We met in jazz band. He was a transfer spring senior year, and we hit it off, and instead of playing with the band, we jammed out in the band closet and talked life and music theory.

While he was no guru, he had some experience, and he was one of the few and first people that had access to real LSD-25 (he was from a hippy town in CO). At the time, I was extremely interested in being able to see the world differently. I was suicidal, and desperate to escape from this internal mental hell that I had been living with for years, and trying to escape by more destructive means.

The first experience entailed a sleep over. We each took one hit. It wasn’t that potent.

It really didn’t do much. We talked about life forever. Girlfriends. Family. Just life. Laughing. Listening to stories.

I was expecting mass hallucinations, but there was none.

Just colors. Everything had more potent color. Vivid. Almost a halo of rainbow. I had a giddiness.

But no hallucinations like I was expecting.

We walked some suburban woodlands for a bit and everything was magical and exciting.

I couldn’t sleep, and was hoping for the marshmallow dinosaurs and electric zebras to manifest, but they never did.

The whole experience changed what I thought of psychedelics. I thought it’d be a more visual experience, but it ended up being much more psychological.

8-12+ hours in total.

*

My first time on mushrooms I was in a group of best friends. My friend and I had ventured into Florida cow pastures, donned in camouflage, the days after rainfall and had picked a pound or more. The Internet was crude back in 05, but we found resources for safely identifying them.

As a group of 7, we divided evenly and consumed. Probably 5 shrooms a piece of varying size. They were not dry. We ate with brownies and milk.

It was intense. Hilarious. Colorful. At times overwhelming. Smiling. Laughing. Confusing. We walked, we talked, we looked at the moon and stars, examined frogs and flowers and grass and trees.

All in all, a lot of bonding. It was an amazing experience.

4-6 hours in total.

*

Dosage is approximately 100-150mcg per tab. If it’s older, and not well kept, potency will diminish. Liquid is harder to determine, but one drop is approx the same as one tab.

If you take 1 tab, don’t expect anything dramatic. Mostly a body trip. But depends on mindset.

If you take 2 tabs, you will have a more powerful experience. More visuals.

As you take more, the trip is more intense. With that intensity comes a lot more unpredictability.

Your mind produces all kinds of images and connections, and you can get absorbed in those manifestations, for better or worse.

*

For any trip, set aside the day.

For LSD, it takes about 30-90 minutes for the initial effects to begin.

There is a period where you begin to peak— anxiety heightens, excitement peaks, things begin to jitter and perceptions loosen. There is usually an uneasiness, a giddiness.

This state is dose dependent, but usually lasts between 2-6 hours.

After the peak, the come down and “reintegration” can last another 6 or more hours. This period the mind is no longer “peaking” with energy. It’s making sense of the new perceptions, and integrating them back into a functional whole.

There are major perception changes on a trip. Senses. Time. Space.

Things and perceptions warp, and you gain an awareness of how flimsy and unreliable our perceptions really are.

When you go to sleep, you wake up as though nothing happened, except that you have memories of this experience that resemble a powerful dream.

There are no negative side effects, other than how powerful the experience was, how deeply it affected your notion of reality.

I usually feel very refreshed, as if the world was anew. Like the cobwebs have been cleaned and the fog lifted. There is a clarity.

*

One thing I always tell others and remind myself is that the entire trip is a manifest of my mind.

It’s not outside me, it’s inside me. As a result, there is no reason to lose control.

Do not react hastily to thoughts and feelings and perceptions. Accept them. Embrace them. Reflect on them. They are you. They are apart of you.

You possess them. Do not let them possess you.

Do this, and you will never have a bad trip.

I have safely tripped more times than I can count. Well over 100, with dozens and dozens of people.


Thanks


Any tips for approaching such experimentation in a relatively controlled manner?

(I've always been keen to try, but have avoided so far due to an unpleasant childhood experience when administered an opiate painkiller, which resulted in nightmares with conscious flashbacks for months.)


Find someone who likes them, but is generally not too eager to speak about it - these are usually quite knowledgable but also realise the implications of social agenda coming with the use. I would be wary of anyone who is too much of a hippie, in a way. Ask the person of the implications: anyone who’s _just_ positive about the effects is probably a liar.

Find a nice time: for example, leave one-two days after your week-long vacation for a trip. You’ll have a clear mind and will be well-rested, so nothing to remind of a possibly stressful job.

Trip with the person from the first paragraph. One thing that I find is way more highlighted in people who are fond of psychedelics is knowing that people change when they trip and they expect that. So should be not many questions asked.

I would say approach the setting the way you would approach your therapist: personal stuff should remain in Vegas; and it will be a better trip if you can expose yourself.

Also the most imprtant part: don’t expect to feel “better”. It’s a two-sided experience, where it may swing you towards both depressing and incredibly positive. You learn how to manage that, but one thing that psychedelics are not is an escape.


This resource: Maps.org

https://www.maps.org/resources/responding_to_difficult_psych...

It’s all about mindset and setting.

We could discuss what that entails, but that’s a long conversation. Good attitude, good vibes, safe setting, comfortable and familiar. In your home. In familiar nature. I’d avoid public places and people.

And it’s preferable for the first number of trips to have a safe and understanding “sitter” or “guide” there who is reliable and calm and supportive.

As you get more experienced, you can explore the bounds of set and setting, to push your mind to places for therapeutic purposes.

Psychedelics amplify whatever thoughts or surroundings you’re in. They turn up the volume, so to say, for good or ill.

The bad trips are the most therapeutic. You’re working through repressed thoughts and feelings that otherwise go unnoticed or denied or suppressed as a natural psycho response to pain.

Ridding self deception is the root of all therapy.

When that negativity comes to mind during a trip it’s often uncomfortable as hell. You work through it. You accept it. You embrace it. You see it in the right light, with the right perspective.

What you don’t do is resist thoughts or feelings or experiences. That only causes more problems.

You can’t run from yourself.


> What you don’t do is resist thoughts or feelings or experiences. That only causes more problems.

IMO MAPS are irresponsible promoters of psychedelics.

If you are on a high-dose trip, you lose much control of your thoughts. I have read that some medical experts administer high doses in the hope to avoid bad trips often encountered with low doses.

What if your unwanted thoughts and tendencies must be resisted to prevent further misery ?

Examples:

- Try to stay calm and refuse to succumb to overwhelming terror and panic as reported on this web page.

- Try to stay calm and refuse suicide as reported on this web page.

- Try to stay calm and refuse thoughts about murder as reported here: http://www.dazeddigital.com/artsandculture/article/29599/1/a...

Do not use psychedelics to solve problems on your own. https://psychonautwiki.org/wiki/Set_and_setting

Let medical experts (therapists) use psychedelics as medicine as they see fit.

https://www.rollingstone.com/culture/culture-features/the-ps...

https://www.livescience.com/16287-mushrooms-alter-personalit...


Controlled? 4 grams of mushrooms will be anything but controlled - thats the whole point. You'll be swirling in the primordial energy of chaos and your rigid mental structures will be shred apart in an ocean of absurd humor.


I found this resource quite interesting:

https://www.youtube.com/channel/UCn8V3KNSgDr1Dai77_y8JrQ


Have a thorough read through this: https://tripsafe.org/how-to-take-shrooms/


Wouldn't that argument go both ways? You say that psychedelics cured your depression. Then doesn't it stands to reason that they also can cause depression? The argument I've heard from psychonauts is that you should be careful and treat drugs with respect. For example, if you are tripping you shouldn't not have any weapons such as knives within reach. But given how dumb the average person is, I wonder how effective such advice is.


Anecdotal info warning:

A few years ago, I thought I was completely incapable of feeling happiness. I hadn't experienced it for a long time and was completely numb. I was chronically depressed for 4-6 years.

I took shrooms from a friend at a security conference completely unaware of what I was getting into. For the first time in _years_, I felt truly happy. I have no idea, physiologically or psychologically, what happened, but when I woke up the next morning my entire world changed -- I didn't feel numb anymore.

That day, my chronic depression ended. I have been depression free for a few years now. We _need_ more research for this.


I had a friend who was suicidal, and mushrooms were the only thing that helped him. He'd feel better for a week or two.


I don't have any anecdotal stories to share. I just like shrooms.


Counterpoint for shrooms

1. I took magic mushrooms (well truffles, Amsterdam, sold in smartshops, i.e. legal) and I felt a bit uncomfortable in my body and I felt like a kid.

2. I took magic truffles again (again Amsterdam) and I felt a lot uncomfortable in my body and was contemplating suicide. Fortunately I had on gray brain cell left that said "you can kill yourself, but only if you agree on it when you're sober and it's one week later." I locked myself in a bathroom with no windows. Yes, I could hurt myself in the bathroom, but I was fortunately to dumb to know how to do that. When the effect started cooling down it was a mix between a really bad trip and a really profound, meaningful yet really painful trip.

When I came out of the trip and felt sober I got a lot of data to analyze about myself and that definitely helped me. Yet, god forbid if I didn't have that 1 gray brain cell that realized that I was on truffles and therefore not in my right mind. Needlessly to say, when I was sober I decided to live because life is one interesting big trip anyway :D

One thing that I am realizing more and more: I really like myself sober. When I am sober I am capable of keeping my emotions in check. It's easier to love myself and all those things.

Nevertheless, I am grateful for the insights.


I can echo this sentiment, as a normally soft-spoken guy who was arrested while completely out of his mind on psilocybin. My perception of reality was utterly shattered; I thought I had died and that my mind was transported into a realm of eternal torture. I'll never forget the dread I experienced while being forced to the asphalt and handcuffed by police officers on the side of the road. They took me to a hospital where I believed the medical staff were preparing to physically mutilate me (keep in mind, I was handcuffed the entire time...I felt helpless). When a nurse asked my name and address, I just broke down and started bawling. Apparently they gave me a sedative, and I woke up later to find my family sitting around me crying.

Psychedelics have an amazing propensity for good, but they can also destroy you. Tread carefully.


Sober trip sitters are a requirement, in my experience. Like, cigs and alcohol at most for them


Agreed about the trip sitter!

In fact, my downward spiral was instigated by another person who was tripping with me. He told me we were severely dehydrated (no, we were just severely high) and needed water asap. This prompted frantically running to a residential area asking people for water, and the rest is hell.


Seems like you were missing the three most important parts of a safe psychedelic experience: Set, setting and a trip sitter.


Sounds like it was a fake LSD, more like dxm or something


It is entirely possible that this was real LSD. To believe that the "real" stuff can't cause these kinds of psychotic episodes is absolutely naive. It is also very unlikely DXM would ever be passed off as LSD, the dosage range is in the 200-800mg area and as such is IMPOSSIBLE to fit on any standard blotter. DXM is also a disassociative drug primarily effecting the NMDA receptor sites in the brain whose effects are markedly different from the sertonergic-centric tryptamine effect produced by LSD and related substances.


It could have just been LSD.

Going into a trip with anything weighing on your mind, or any stresses or worries can lead to a bad trip.


I am overall pro psychedelics but I have seen them harm people first hand as well. They should be treated with a lot of caution and respect. I totally understand the urge to evangelise them but keep in mind that you're taking on a lot of responsibility when you encourage people to experiment with their brain chemistry.


I hear ya. I’ve yet to see it negatively effect anyone other than a bad trip, which, seen in the right light, can be a therapeutic experience.

But I know they need to be respected and understood.

I also realize that some people with a family history of mental disorders like schizophrenia, would be better off staying away.

Like, some people have used psychedelics, and they go crazy. But how many of those people were crazy to begin with? How many would end up like that if they never tried psychedelics to begin with?

I tend to think that the fear is over dramatized.

But I do emphasize respecting its use in a profound way.

It changes you.

The upside is that real LSD is so rare, the chances of people finding it are slim to non. It’s distributed by so few people.


I watched a good friend freak out in front of me on a bad trip. Almost thirty years later he's still not the same and needs antipsychotic medication to function. This kind of thing isn't common but it can definitely happen.


The rate of psychosis in clinical studies appears to be very low, and they carefully select research subjects.

I would suggest that psychedelics cannot take a person with zero risk of developing psychosis, and make them psychotic. There are many apparent triggers for mental illness eg a failed relationship, a drug binge, losing your job, giving birth etc, and we don’t treat these as causal events. Psychedelics are most likely no different. People at risk of developing psychosis may have a greater willingness to try psychedelics as well, creating a biased sample.

If we ever do get regulated access to psychedelics, it will need some process to exclude ‘at risk’ persons. This will be crude and highly exclusionary at the start. Over time, genomics and brain imaging may allow more careful selection of those who can take psychedelics safely.


> People at risk of developing psychosis

Psychosis is an episodic condition caused by metabolic failure. Contributing factors include malnourishment, alcohol withdrawal, chronic stress, certain prescription and OTC drugs, street drugs, etc. People would recover from psychosis if given supportive treatment - good nutrition, B-vitamins (liver, yeast, etc), appropriate pro-metabolic prescriptions, naltrexone to keep them off alcohol, etc.

My observations of the standard treatments forced on "psychotic" patients is that they are only useful for preventing the patient's recovery. My aunt's friend was always sort of 'off', now she's dying of liver failure. Didn't know until now that she's been on maintenance antipsychotics for decades, even though the trigger for her episode concluded decades ago.


It can happen with various meditation and yogic practices as well, and the effects can be just as severe and long lasting. I suspect that some people’s minds are in an unstable equilibrium that, when perturbed, sends them way off balance, and it is a state that no one would have been privy to before some traumatic experience acted as a trigger.


It's entirely possible that LSD uncovered or accentuated an underlying flaw in your friend's psyche...


I don’t understand this common response at all.

If I prescribe penicillin to a patient with a pcn allergy, the fact that I “uncovered an underlying flaw” is irrelevant. Pcn is dangerous to them and should not be prescribed to them.

This is true, in one sense or another, of the majority of adverse effects people have from medications given in therapeutic ranges. It’s basically what having an adverse effect -means-.

It doesn’t mean that medication shouldn’t be given when appropriate, but it’s not a rationale for deflecting attention from the risks of the medication.


The difference is that penicillin allergies can only be triggered by penicillin (or maybe penicillin-adjacent analogues). Mental illnesses and psychedelics don't work the same way.

Psychedelics bring these issues to the forefront, but they don't necessarily cause mental health issues, as the same issues could happen without LSD. I understand what you're trying to express with your example of penicillin, but it's not the same thing.

In my opinion, it would be more accurate to compare psychedelic drugs to activities like meditation and fasting, which also have a risk of anxiety, discomfort, and bringing out dormant mental health issues in some people.


A good mindset of psychedelic use is that you’d like things to be brought to the surface so they can be worked with and integrated.

This is precisely what makes them such useful tools for things like PTSD and why it can be a bummer if someone does Molly at a rave and winds up with a memory of being molested and her friends are too busy doing K to talk with her.

In a safe and supportive setting, this is exactly what can help people heal.

It’s when things get uncovered but not fully released and processed they can occupy ones life.

A good psychedelic therapist or sitter should be able to help someone integrat a current or former bad trip.


> In my opinion, it would be more accurate to compare psychedelic drugs to activities like meditation and fasting

I've done all 3 of these (meditation as in mindfulness), and I disagree.

Of these 3, meditation is the most harmless. It is relaxing, not discomforting (I'll hook into this again at the end of my post).

Someone can start meditating or fasting without guidance (though I recommend guidance in both cases, especially concerning fasting) and resume normal life whenever they feel like it. With psychedelics, that one doesn't fly and if you do meditation in a group such as a 10 day Vipassana course or are in a religion or cult being forced to fast then you might also feel the same pressure. But that's an outlier; in general, meditation doesn't have such -or any- pressure. It is relaxing.

Finally, I've followed a mindfulness course for people with autism and there is no such thing as that with regards to psychedelics. The psychedelics also affected my autism, and in some situations made it much worse. All of that while I wasn't aware I had autism!


> It is relaxing, not discomforting

Meditation practice is not relaxing at all. The effect after meditating might be in part feeling relaxed, but in general meditation is pretty hard work.

This is probably a very common misconception, you see all the pictures of people meditating at the beach in front of a beautiful sunset and think that meditating is like going to the spa, when in fact meditating is much more like the mental equivalent of going to the gym.

Also, in many occasions (especially during a 10 day retreat like Vipassana), it can be very uncomfortable if not outright physically painful (although usually never dangerous).


For me mindfulness is far more relaxing than studying, watching a TV series, working, programming, etc (all "active" things). Never mind socializing which is the opposite of relaxing to me, ALWAYS (autism-related). Although it differs per technique (some are easier and fit me more than others).

Especially the effect after it makes that work more fruitful, since for various hours I'll be less tense and more focused. For example, it'd make socializing more relaxing.

Those are 2 very valid reasons for me to call it relaxing. Then again, I find running and listening to certain music also relaxing. Because after a while, I get in an automated flow ("trance") akin to meditating.

The 3rd reason is that if I'm rather tired, mindfulness can potentially get me to sleep. I often (almost daily) do it before I go to sleep, and it aids me to get to sleep. I much prefer it over: overthinking, fantasizing, or masturbating/sex.

Its already painful for me to meditate whilst sitting instead of lying but one gets used to that. Its just untrained muscles getting trained. As long as you don't strain yourself, you're fine.


Psychedelics are not just spiritual/mental. They can literally alter your brain chemistry and, in rare cases, cause severe adverse effects. There need to be more studies done on the brain chemistry so we know how to predict and prevent those adverse effects.


This is the common response from proponents of LSD. To them, it's never the LSD, and instead the adverse reaction must be because the person had a mind that was predisposed to some sort of mental illness.

Even if it's true that someone has some kind of latent / dormant condition that is ultimately triggered by the LSD, then the act of taking the LSD itself was the catalyst, and the person would have been far better off not ever having taken the drug.

The drug is illegal, and the argument growing up was that the "government was suppressing free thought" or whatever nonsense was being pushed, but the reality is that such a drug is dangerous and absolutely does hurt people. Whether connected to a predisposition of mental illness or not, it's not a hard connection and people should be extra cautious when considering whether to engage in such behavior.


Care should be taken, like with any substance we ingest. However, I disagree with your premise.

We do not know if LSD was in fact the catalyst. We don’t know if the people who got ruined after taking a single tab of LSD actually took LSD or some research chemical (which are quite commonly sold off as LSD).


Some research psychedelics are more dangerous physically, and certainly less researched, but in terms of psychological effects, all psychedelics are generally pretty similar. It's silly to assume LSD is somehow significantly less likely to cause psychological trouble.


Yeah, 2CI is for example very dangerous psychologically, and I’m sure it gets sold as LSD when an unscrupulous dealer has excess inventory.


>The drug is illegal

>but the reality is that such a drug is dangerous and absolutely does hurt people.

With this reasoning, skydiving, base jumping, and even the act of simply driving a car should should also be illegal. We let people do far more dangerous things, yet keep them legal. There is another reason LSD & most psychedelics are illegal. What that is, I don't know.


What's your evidence that those people are worse off having taken the psychedelics? You can't know the counterfactual isn't that those people who respond poorly to the drug would have had a similar mental break without it. Until the drug is studied rigorously all we have to go on are conflicting anecdotes. That said in the face of a lack of reliable information caution is warranted.


Even if that person would not have taken LSD and would have had a psychotic episode 5 years later due to the underlying issue, that's still 5 years of good health lost because of LSD.


Or it’s 5 years less of post-treatment life.

We can make random guesses all day about what’s a good outcome but how about we leave it to medical researchers to actually figure out what’s safe and beneficial?


It seems pretty delusional to just say these people would have spontaneously lost their minds even if they didn't do extremely powerful mind altering drugs.


It seems pretty delusional to make conclusions when you don't even know if they really took LSD or something sold as LSD, but actually dangerous, and are missing basically all other important data other than "they took something and then became crazy", while the then in the sentence means "after that", as in time, not "because of that".


It’s literally guaranteed that some of them would have.


So if someone takes any medication and strokes out, has an MI, or stops breathing, we can't blame the drug because maybe that was going to happen anyway?


Usually, yes. That's why we haven't banned Tylenol.


>The drug is illegal,

Only in certain contexts (ie. some instances of interstate commerce).


I agree, it only should be available to those, who are already in danger by pre-existing conditions like chronic depression or other similar serious mental conditions.


That’s the point - there are other, slower, safer means to effect positive change on your mind that don’t run the risk of fucking up your brain from some random effect you had no way of predicting. The point is that it’s effects are powerful, which is why there is finally a revival into what exactly is happening.


This isn't a useful distinction unless you can reliably identify the flaw before the negative impact of LSD. Without a detection mechanism, this is as actionable as "LSD does bad things to some people"


It probably did but that flaw wasn't obvious at all beforehand. He was a bit eccentric but also a really bright and funny guy with a lot of friends and a very dedicated student.


I've seen this too but not from just one trip. I've seen heavy users kind of never come back.

I suspect your friend had latent psychotic tendencies. Would be interesting to look at family history.

These are powerful drugs that seem capable of both helping and doing harm. They should definitely be used with care, studied, and not abused.

Of course what the war on drugs did was to ban the scientific study of these things and push them exclusively onto the street where they did get abused.


The existence of undiagnosed disorders and the potential presence of effective coping skills/supportive stable home environment/unstressed personality/late-onset symptoms would preclude reliance on prior indicators of determining fitness for a given psychedelic.

Family histories are not always clearly diagnosed. That hypothetical uncle you've never met and no one talks about? Unknown mental health flag.

Self-diagnosis of a mental/emotional state that calls for drug-taking is itself a clue that not all is so normal in the individual's mind--or is it something wrong in the world the person wants to relate to better? Who can know but the one supposedly experiencing an unnaccepted state? Observing/deciding/dosing by the selfsame suffering/diagnosing/tripping individual sounds risky, because if the downside is a long future of some degree of insanity, it is only a variety of Russian Roulette.

To allow scientific studies, fund them, possibly create therapies is to also conquer the stigmas involved in substantial ways and that process is tectonically, multi-generationally slow (or impossible).


What was the set and setting for your friend?

What was going on in his life at the time?

Who was with him and how did they work with his “freak out”?

It sounds like he lacked the set, setting and support to integrate that experience in a healthy way.


Someone does not need to have a "family history of mental disorders" to become an acid casualty. Some people simply have a bad reaction to the chemical and there isn't a reliable way of knowing in advance how a person might react to it.


How do they know if what they’ve taken is actually LSD-25, and not some research chemical?

Research chemicals pawned off as LSD is more common than ever. They are dangerous psychotic inducing deugs.


How do they know if what they’ve taken is actually LSD-25, and not some research chemical?

Anyone who has become an ‘acid casualty’ was dosed with these dangerous research chemicals, and everyone who was just fine had legitimate LSD?


Are you suggesting that’s impossible or improbable given the prevalence of fake LSD as well as research chemicals being sold as LSD-25?


My implicit suggestion was that the viewpoint expressed in my comment (as a question) is a ridiculous logical fallacy.

Reading the other comments I see that others have expressed the same thought.


It’s a hypothesis.


I heard LSD is rarely synthesized now and instead people end up with research chemicals (now scheduled) like 2C-B instead. Do you know if this is true?


True. In fact chances you're buying LSD nowadays is almost zero. And I suspect this is the reason of many bad experiences described in this topic


Where do you get that information from? What are people taking when we see articles on HN talk about the benefits of micro dosing?


It's not. There are reliable LSD vendors on the dark markets.


Test kits, test kits, test kits, TEST KITS. This whole thread needs test kits.


Do you have any research to suggest people can become an “acid casualty”?

This seems to be more lore than fact.

And recent meta analysis shows that psychedelic use has no negative impacts on mental health (and in many cases, is beneficial).


Can you cite research that backs that up? I have a friend who it brought out/caused his schizophrenia. I understand it may have occurred naturally eventually because he has a family history but having it occur when he was 20 is much worse than later in life.

It’s incredibly irresponsible to say it has no negative impacts without more research being done in the area.



This study seems to suggest classical psychedelics do not cause mental illness which I will not argue against. However, as someone diagnosed as schizophrenic in 2012 and now considered bipolar with pyschotic features my last use of LSD caused a pyschotic break. I had a great trip, but I took the drug at 9pm before a festival and by the time I made it to 6am I could not slow down the frentic pace of thoughts in my brain and calm down enough to sleep and my pyschosis manifested itself despite my experience with hallucinogens and previous pyschotic episodes. I was in a stable state and it was the night of lsd that destabilized me. I haven't experimented with psychedelics since even though I have had some of the most powerful and positive experiences on lsd and mushrooms. It is not worth the risk of ending up in handcuffs again. I do not wish the mental ward on anyone. So my advice is respect these substances and your body because altering your mind opens you to possibilities beyond considerations of sober thought. People like me should not use these substances, and you may not realise you are like me until you do. I knew I probably shouldn't but my experience led me to believe I could handle any trip, that an lsd trip is a drop in a bucket compared my psychosis, but I learned that drop was all my body needed to propel me into another episode.


I’m sorry you had such an intense experience!

I was diagnosed with schizophrneia and Biploar. I found that mdma in a theraputic setting helped me heal the underlying condition and resulted in an elimination of symptoms.

I’ve also had psychosis induced by psychedelics, however I also saw how the psychosis was a result of deeper held beliefs that weren’t serving. The psychosis ended up resolving with a much deeper sense of self and compassion.

That said, with a clear understanding of psychosis, how to work with and integrate it, and a theraputic setting for psychedelic use, folks might want to avoid it.

Psychedelics helped me heal without medication.


You could say the same thing about anything that anyone has ever had an allergic reaction to.


I’ve seen a friend become semi dependent and kinda disassociated from reality after multiple times a week use of various research chemical psychedelics. It seemed to bring out some underlying bipolar like condition.

Anyway; also a strong proponent, but I’ve seen the potential harm as well. On the balance it seems worthwhile for many people, and good for many people to try a little LSD at least once.


Research chemicals are dangerous.

They’re mostly all synthetics derived from amphetamine class of drugs like MDMA.

2CE. 2CB. 2CI. Etc. and countless others. No one taking them know what it truly is.

They are dangerous. And more ubiquitous than LSD-25.

You can never be sure what you’re getting. You can OD and have a psychotic episode.

I do not classify them as therapeutic psychedelics, and always advise against.

If you ever take a tab of LSD and it’s bitter or metallic, or anything but absolutely flavorless or just paper, do not take. Spit it out.


This is an idiosyncratic opinion to say the least.

2C-E, 2C-B, and 2C-I are what they are, single compounds, just as LSD-25 is. They are phenethylamines, related to mescaline, the substance for which the term "psychedelic" was coined.

They are synthetic, as is LSD, and have a wide therapeutic index. Being less potent by weight, it is easier to measure a specific dose than with LSD, which is commonly put on paper or taken in liquid form.

Getting "puddled" from a bottle of LSD is a more likely route to a psychotic episode than anything 2C-I or 2C-B have to offer; 2C-E is a different beast.

It's fine that you have these opinions, I guess. It's just that most of them are wrong and I wouldn't want others to be mislead.


The really dangerous stuff is the NBOMEs which were being sold as LSD maybe 7 years ago. This is why we need legalization, so people can be sure what they're getting.


Anecdotally I’ve consumed 50-75 100mcg doses of 1P-LSD over the last year and found it almost indistinguishable from LSD. Not to mention easier and safer to obtain (directly from a research lab).

Obviously there is no research on long term effects at this point, and there may never be, but for my personal therapeutic rituals it’s affectiveness is the same.

It’s also worth noting that I’m not microdosing, which you may have assumed from my doses over time. I’m taking it once a week at an average dose of 300-600mcg with a 1-2 week break every 4 weeks (obviously I didn’t start at this dose when I first tried it). Along with other health supplements and exercise just so were clear.

I am an experienced psychonaut, but I’m not a doctor, and I’m not here to champion 1P-LSD nor my personal rituals. But this is my experience.


Cool! Glad to see mention of 1P here. I'm a fan of it myself.


Isn't 1P-LSD the ones that metabolizes into LSD-25?


AFAIK it has not been proven if it breaks down into lsd-25 of if 1p itself fits into the 5-ht receptor as it’s own in vivo.

>It has been theorized that 1P-LSD may act as a prodrug for LSD. While 1P-LSD shows only 38% the potency of LSD in mice, LSD is detected via LC-MS when 1P-LSD is incubated in human serum. Follow-up studies are currently being conducted to compare the affinity and selectivity of LSD and 1P-LSD at 5-HT receptors, and to determine whether 1P-LSD is hydrolyzed to LSD in vivo.[1] Otherwise, it is possible that 1P-LSD may be capable of exerting its own psychedelic effect.

https://psychonautwiki.org/wiki/1P-LSD


This is a bit reductions. There is a lot of research chemicals that are very safe analogues, e.g. 4-ACO-DMT or 1P-LSD. Often times more safe because when you purchase these its from a lab that does testing and you know exactly what you're getting.

The real danger of Research Chemicals is the large amount of cheap drugs of other classes produced that have similar effects and are labeled and sold as LSD. Very few people are buying those type of drugs and taking them on purpose. And they are incredibly dangerous.


It's worth noting that people can know what they are taking (within a statistical certainly) by sending their substances off to somewhere like Energy Control, or another analytical lab for testing. Most people don't do it, but it is possible to know what you've got.

https://energycontrol-international.org/


Although far from non-existent, none of the chemicals you list are more ubiquitous than acid nor usually sold as acid. Actually, their effective dose range is about 100x that of acid and it would be hard to impossible to fit them on a tab.

NBOMEs are something you did see sold as acid especially a few years back, so I'm not saying you shouldn't be careful. The difference in effect is fairly easy to tell, though, and I have no doubt most stuff sold is the real thing. There are some closely related and nearly indistinguishable compounds, but as far as I know, they are about as hard to synthesize and should have a similar risk profile as LSD.


This seems to me to be a very dogmatic approach.

One can be sure of what one is getting with proper testing. Some are dangerous, others less so.

Personally I enjoyed my experiences with some of them.


>And more ubiquitous than LSD-25.

that is CERTAINLY false.


> But I do emphasize respecting its use in a profound way.

You did not emphasize in any profound way.

You did imply though that it invariably changes everyone, and never was anyone you know changed for the worse. So it changes everyone for the better. But you ask, surely because you are not sure, whether those who were crazy afterwards had to be crazy to begin with. So, the only thing you really emphasized was your ignorance. What does that mean to you? Everyone is a little crazy to begin with. Thus estimates about sanity are rather distorted and a small sample group not enough, especially if you are biased by preoccupation.


Real LSD is not that rare. You know, people can and many do have their stuff tested. There was a bit of a dry season in the early 2000s but not anymore. This is variation of the stupid old "clean" vs "dirty" acid myth.

Anyway, you're probably right in the sense that there are only a handful of original sources for it. But once you get the production going, you quickly end up with a crapload of doses.


Psychedelics such as LSD, Psilocybin and Mescaline has the ability to treat long term depression. They seem to allow you to step out of the box in other words get you a truly new perspective on the world. From what I can understand these drugs alter the brain area responsible for emotions the amygdala. I would go as far as to say people with long term depression needs reprogramming of their brain and one way to accomplish that is Psychedelics. This is not something one should self administer when depressed. For those who tried above substances did it change your brain for the better? Also I belive Psychedelic drugs could help people with autism spectrum for some. People with autism also be helped with a different perspective on the world.

Psilocybin and Depression https://clinicaltrials.gov/ct2/show/NCT03380442

https://www.independent.co.uk/news/health/psychedelic-drugs-...


> For those who tried above substances did it change your brain for the better?

That's a tough question to answer, but I can share my story and maybe you can glean from it. The truth is, drugs can do incredible things for the mind, body and soul, but the person must be able to handle the intensity, and their own craving.

My upbringing was pretty rough: parents divorced when I was young and I was raised by my southern-Christian grandparents since I was five. My parents were very poor and my grandparents had already raised two kids on low income. I was fairly depressed growing up for many reasons related to my natural life. I'm first generation in my family to graduate University, let alone with a STEM degree, and my career provides a better salary than anyone in my family has ever had. It was a pleasant surprise for my family, and you'll understand after the next couple of paragraphs.

I had stated smoking pot in middle School, alcohol came next, then ecstacy, codeine, mushrooms, and Acid, all before I graduated high school. College had shown me MDMA, DMT, cocaine, various opiates, and some research chemicals my friend kept around. Recently (late twenties) I had experimented with ketamine for the first time.

In high school, when some friends and I started getting into ecstacy, it didn't take long before some of them became habitual users. At one point my friends would be taking it at school. I took this as a cautionary red flag, and reigned in my ecstasy use at the time. Sure enough, those friends became addicted to the sensations, and took life paths that would lead them to misery. This was a vital learning moment in my life.

Around that same time in high school, I had arranged with other friends to take mushrooms together at their house. I ended up taking about 7 grams, which is -plenty-, and about twice as much as the most I've ever taken. The effects were good when they were good, but really bad when they were bad. Most of the time I couldn't arrange proper sentences, regular body functions seemed like foreign operations within myself, and everything I looked at had a Kaleidoscope-esque effect on it. At one point I summersaulted into my friends wall on the way to the bathroom, where I proceeded to fail to remember how bathrooms work, and pee all over myself. This experience has since kept me distant from mushrooms.

Right into college, I had joined a political activist group and started making friends. While driving together to an overnight rally at the neighbor University, some friends in the group revealed to me that they regularly consume large amounts of psilocybin mushrooms. I didn't end up getting to know them well, but they seemed like nice and well-intended hippy-types attending college.

A month ago, I went to an epic-level music festival where the only thing more prolific than music and water were drugs. While walking to find a restroom at sunrise, I came across a guy hanging in his campsite mumbling to himself. We started some conversion and he came back to our camp to hang. Later he revealed to us that he was coming down off a twenty strip (20 hits of LSD). That guy made for some interesting conversation.

For me, more than any other type of drug I've tried, psychedelics do best at opening my mind. Other drugs have their purposes, but from these drugs, the effects are truly interesting. I feel like I'm able break down mental structures that exist in my mind, and recreate them in different ways, either for a real goal (relief from depression), or just for fun (hallucination, creative outlet). Once I found my footing with psychedelics, my experience became centered around allowing weird and non-conventional thoughts to take over my mind, until I I'm rethinking how everything workes and why things operate in today's life the way they do, and how with some wild creatively, we could have an entirely different reality that's more beneficial to us all. That, and dancing.


For those that haven't tried psychedelics but are curious about them in a personal growth / non-recreational way, on the Joe Rogan podcast I heard a good metaphor along these lines:

Imagine your brain as a snowy hill. Each decision you make is like sledding down the hill, causing a slight indentation in the snow. The more times you make a decision, the deeper the groove, the faster you make the decision and the harder it is to try something different and escape the groove. Psychedelics is like fresh powder on the hill won't the grooves away so you can try new ways of thinking / new routes down the hill.


It's not a bad analogy.

I will add this: the shape of the hill stays the same, and mostly that fresh powder will melt back into those old ruts... the changes that these experiences bring seem, to me, more about knowing the ruts are there then they are about changing things in our lives.

The change comes from the awareness of what can be done, because formerly "natural" things that are "just what people do" start to seem like artificial, learned behaviors. That's a powerful thing to grok, and easier to comprehend at the level of our nervous system with these substances.

I haven't found these drugs to be super "fun" outside of the non-recreational ways of doing things, but the older I get the more I enjoy things that most folks find exceptionally boring. But I do find them very useful.

For people who people worry about the long term effects of these things; I feel like for most healthy adults, if they "start small" the actual long-lasting effects are pretty minor.

Here's an idea to consider for curious folks: if one or two psychedelic experiences could fundamentally alter your views on your life, you probably ought to consider the deep things in your life more often.


yeah, one of the biggest misconceptions that i had was that it would be "fun" to try psychedelics. it wasn't fun, and it wasn't not-fun. it was different, and it was a learning experience.

the long lasting effects were negligible for me. the biggest change was that i realized i might be "on the spectrum" but it isn't as though it was a life-changing realization.

i agree regarding your final point. i do think that psychedelics are more "helpful" for people who are extremely extraverted or otherwise reluctant to reflect on themselves.


Any time I am given the opportunity to learn something new unexpectedly, I have fun.


There is a certain amount of enjoyment from learning.

I wish that I had not had to see out how badly my drinking impacted my marriage with my second wife when she unexpectedly left me, but it was a thing that I needed to learn.

So I take your point, and I am glad to learn things. In general I find learning an enjoyable experience. There are a certain amount of life-altering, important facts about ourselves that are painful to encounter in any situation.


This is a good intuition for brain plasticity in general, has been thrown around in numerous forms since the 70s. "Sledding" is the least abstract way I've seen it put.


This was from the Michael Pollen episode.


For those who want to walk this road I'll share some insights that I think would have helped me progress faster.

You will need to face every thought that you normally would censor due to shame, those include (usually in this order): sexual thoughts, psychotic thoughts and religious thoughts. Then you will reach true vulnerability and loneliness (which is the prerequisite for truly connecting with others).

Any 'spiritual path' will take you through the same process but psychadelics do it faster meaning there is less control (i.e. less feeling of safety) however this can be a good thing since we often use the control afforded through for example yoga to avoid facing some flaw in our methodology.

As always I recommend patience as the principal approach and an absolute belief that the true nature of the world is 'good'.

The key insight is that everything is about relaxing and trusting the wisdom that lives deep down, it doesn't matter what you are doing, if you approach it in this way with balance and compassion as goals then you can feel better.


...and have a trip sitter.


There are some people in this thread asking for advice on using psychedelics.

If you're in this thread and likely to use psychedelics, please do your research first.

My recommendation is to at least thoroughly read the following resources before beginning:

- https://tripsafe.org/how-to-take-shrooms/ (I started this website, it has quite a few users, and it's important that people who are likely to use psychedelics are aware of this info for everyone's benefit.)

- Then, next perhaps the book "The Psychedelic Explorer's Guide"


I am excited to see more positive coverage of psychedelics. But every time threads like these pop up, there are people who claim to know people who came away from a trip with some kind of psychosis/anxiety disorder. I haven't reviewed the literature in some years; can anyone recommend any modern sources which document rates of poor outcomes post trip? I feel like, while odds are in one's favor, these drugs can be a coin toss, I'd like a better feel for the odds.


I cannot find the author of the quote, nor the quote itself, but it was something like this: "You should take psychedelics and then work hard to experience the same, but without psychedelics itself".

I remember one guy posting about his experience with psychedelics and then with long period of yoga and meditation. Interesting thing was, that he described something similar. On psychedelics it was as if you would take a jet plane and got somewhere really fast. Yoga and meditation, on the other hand, take you same place but you have a time to look around during the process. It takes a lot of time, though, but also is safer.

Interesting may be combining meditation and yoga with microdosing, which should still keep you on the safe side.


My friend in college gave a similar analogy as the quote in the first paragraph.

He said psychadelics can open the door but then you go thru the door. You don’t just keep re-opening the door.


There are several meditations teaching that strongly advise to avoid mixing deugs and meditations. Some, like vipassana, even recommand to stop taking any drug prior practice.


I had an acid trip with an agonizing comedown that made me really rethink my life and priorities. As a result of that day I began the path to go to medical school, despite everyone including my parents telling me it was unrealistic. I'm just finishing specialist training in anaesthesiology and my life is great and I pretty much thank LSD for the whole thing.


Surprised there's been hardly any mention of Michael Pollan's new book. He's the author of The Omnivore's Dilemma and In Defense of Food, and most recently How to Change Your Mind -- mostly about the recent advances in the study and therapeutic uses of psychedelics. There's also an accessible chapter or two on the latest neurophysiology findings on the psychedelic or mystical state of consciousness.

The book goes into some detail about a few FDA-approved clinical trials for MDMA and LSD-assisted psychotherapy underway, some approaching Stage 3 -- these are mainly the result of over 15 years of work by MAPS[1] -- if Stage 2 results are anywhere near as successful as the small Stage 1 trials, we're pretty likely to see legal and widespread adoption for the treatment of PTSD, end-of-life anxiety, and/or depression.

[1] http://www.maps.org/


I'd like to see research comparing the effectiveness of cannabis in small doses, against other psychedelics. If your goal is to benefit the largest number of people, then it makes sense to start with a substance that a significant fraction of the population can access without advanced social skills and risk tolerance.


> Psychedelics Promote Structural and Functional Neural Plasticity

Glad to see public research is coming out on this, and it's not a brand new insight. Pretty sure that's why the CIA were using them in MK ULTRA mind-control experiments.


Drug makers do not understand what it is like to be psychotic and mentally ill. They need to experience them to truly understand how to develop drugs, because most of the drugs are ineffective and side effects are way too strong. John Nash has given up on his medication and instead rationalized his disability for the rest of his life, after his final discharge in 1970.

It's unfortunate many people do not understand mental illness at all, and they think therapy and drugs can be cure people. They cannot. Mental illnesses are treatable, but they cannot be cured.

Okay, I am done. I hate this world. Fuck these medications. https://pbs.twimg.com/media/Dip6Q6AX4AAfq8y.jpg

Look at it. Ain't working. Ain't working, people. They ain't working. Ain't nobody gonna understand. I read enough papers to fully understand no drugs can help.


I would prefer something which promotes neural plasticity without showy side effects.


mnm1 8 months ago [flagged]

Current antidepressant drugs are garbage by comparison but we're stuck with them for profit and stupidity reasons. In the meantime millions who could potentially be helped suffer and die. It's truly hard to justify the current situation on this research and the government's position in letting people suffer and die from such a horrific condition as depression when there might be a solution right before our eyes. Future generations will not look kindly on our stupid, barbaric, hateful society for this.


If you have a neurotypical person, therapy, or psychedelics can bring a lasting result.

But for a certain subset of population, with messed up serotonin pathways, antidepressants are the cure. Just like for a diabetic an insulin shot is.


Messed up serotonin pathways. What does that even mean? The chemical imbalance theory of depression has zero proof behind it and is just something told to patients to alleviate their concerns and sell them on these drugs that many will eventually become dependent on (1). No one knows what the mechanism of depression is or how to treat it. It's just a guess as to why and how these chemicals work or don't. Cure my ass. They don't even know how it works or what is wrong with the patient and you're taking about cures.

1: http://www.afterpsychotherapy.com/chemical-imbalance-in-your...


>messed up serotonin pathways, antidepressants are the cure. Just like for a diabetic an insulin shot is.

We should be careful when saying psychiatry is "just like" biological science, it's not.

"psychiatric diagnosis still relies exclusively on fallible subjective judgments rather than objective biological tests"

https://en.m.wikipedia.org/wiki/Allen_Frances

While it's true many people have experienced positive results with antidepressants (many have with placebos as well), "messed up serotonin pathways" and "chemical imbalances" are marketing slogans, not scientific facts.


I read "Lost Connections" by Johann Hari[1] a couple weeks ago. He spends much of the first section on the research and history of antidepressants. One particularly interesting thing is that drugs that decrease serotonin levels are just as effective as those that increase serotonin. The same goes for drugs that alter levels of dopamine. It seems that a great majority of the effectiveness of antidepressants comes from the placebo effect, and the remainder is somewhat of a mystery. Also, doesn't cure imply something that is permanent and not just a temporary measure?

[1] https://www.theguardian.com/books/2018/jan/17/lost-connectio...


I don't know much about human biology, but if the relationship between dopamine/seratonin and depression/anxiety is more non-linear than linear, then the fact that both increasing and decreasing dopamine/seratonin is effective can make perfect sense. This sort of relationship - where small changes shift an equllibrium and result in a qualitative change - are common in nature and a forteriori human physiology.


Yes it seems totally plausible that psychedelics can help people who had maladaptive experiences or upbringings make permanent improvements, that symptom relief drugs like antidepressants may even stand in the way of. Almost all of the work on using psychedelics to treat trauma bears this out.

On the other hand, if psychedelics increases plasticity, regular use could also destabilize a mind or erode important learning.

Figuring out when it is appropriate to adjust plasticity is going to be the challenge to beneficial use here.

If the current ‘psychedelics cure mental illness’ craze leads to more indiscriminate use, it is going to lead to more terrible casualties before we work this out.


>psychedelics can help people who had maladaptive experiences or upbringings make permanent improvements, that symptom relief drugs like antidepressants may even stand in the way of.

this is my understanding as well. kind of like how a child would never learn how to walk on its own if the parent held it upright 100% of the time.

unfortunately, i think a big problem with the current standard of care is that it prioritizes shutting the patient up -- reducing complaints regarding symptoms -- over curing the patient.

there is a difference; imagine if the "real" effect antidepressants have is to make people more reluctant to communicate negative thoughts to others. the patient would still be suffering just as much, but appear to have improved. the brain is subtle enough for this to be a reality...

obviously i don't believe that this example (which is totally made up) is uniformly the case. but shifting the frame to address the underlying problem of "stuck" or maladaptive neural circuitry via psychedelics could be immensely helpful for patients.

psychedelics would also improve the efficacy of the other psychoactive tool we kind of think is somewhat helpful in some instances of some kinds of cases: therapy. therapy is retooling neural circuitry the hard way -- via repeated activation of alternative thought patterns of nebulous physiology in the hopes of eventually shifting the thought pattern to be adaptive rather than maladaptive. if we had a switch to flip that would enhance neural plasticity, this process would be much faster and much more effective. it would also be much more fraught with chances of inflicting damage, i'd assume.


Are we though? Most of the time people look for a pill solution to major deficiencies in their lives. The doctor isn’t strapping you down and shoving the drugs into your mouth.

Just like blaming the heroine drug epidemic at pharma and doctors, it’s weird how we never look at the individual who’s taking the pills in the first place. Prior to this epidemic we had other ones to which everyone was really trying to pin the blame on something else rather than a combination to include the individual as well.

My buddy is a doctor and he’s aware of the lies/illusions patients live in. But if the doctor suggests such things like “exercise/clean up diet” for a few weeks before progressing to another step, that patient will never come back. They will also downrate the doctor on yelp like sites. So it becomes a troublesome proposition for that doctor.


Sounds like your friend decided to optimize his medical recommendations based on return business and has found reasons to blame the patients as a justification for operating on business metrics. The patients are probably doing the same thing, who needs to pay a doctor to tell them to diet and excercise?


Not sure what you're asking. If you're asking if we are stuck with shitty drugs that only work sometimes and require the patient to be dependent on them, I'd say yes. The legal consequences are too severe to argue otherwise. Even carrying out legitimate scientific studies is close to impossible. Of course one should lol at the individual. One should also look at society's role in promoting depression. But you're not going to fix society so you're not going to fix the individual who is made sick by that society. People need friends and contact with other people, not the isolation our society provides. They need stability in life and purpose, not the unemployment and abysmal life our society provides for most of its members. We can't fix these problems. Blaming the individual for things that are out of his control is silly. Making him dependent on a substance to function is criminal. All the while we have medicine that one doesn't need to be dependent on and can be used once in awhile for recovery but researchers are punished with jail time so that we increase the profits of the company making the drug that doesn't work. Who wouldn't rightfully be depressed in such a society and who wouldn't be angry at people who suggest that the individual's own behavior rather than the helplessness and hopelessness of our society are his fault alone (as our society does with this issue)?


The non public health care system you have in the States just looks like such a joke sitting here in Europe.




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