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Alterations in glutamate and the experience of ego dissolution with psilocybin (nature.com)
167 points by kjeetgill 71 days ago | hide | past | favorite | 187 comments

I'm kind of hoping this puts the nail in the coffin with researchers trying to separate the psychedelic effects from the anti-depressant effects so that they can turn it into some kinda pill people have to take every day.

> they can turn it into some kinda pill people have to take every day.

I feel like this model is a perfect example of how the incentive structure of the pharmaceutical industry runs counter to pursuit of the best outcomes.

From what I understand anecdotally, psilocybin taken in moderate doses can have beneficial effects on depression and anxiety which last for weeks or months after the dose. This would be an amazing result by all accounts. A treatment which can be done every 6 weeks and still be effective would mitigate a lot of risks, like possible dependency and any toxicity which might be related to prolonged exposure. It seems to me that gets much closer to what we would refer to as a cure than a treatment.

But it seems like most of the clinical research is going into micro-dosing: i.e. how to make this something you would take every day to alleviate symptoms. I just don't understand the benefit of this approach other than the fact that it might be a better business model.

Moderate does trips aren't for everyone. The HN crew is full of novelty-seeking, curious, open-minded explorers, already drawn to this sort of experience. Your average, vanilla soccer mom who is largely okay with life but struggles with panic attacks because her brain isn't great at damping the amygdala-cortical loop, may not necessarily be ready/interested in a trip through psychedelic space.

I think the answer to that is to slowly increase the dose over a number of sessions. Starting out with microdosing to get used to the body feeling, then getting used to visual disturbances and the altered mental state, and then graduating to a level that can unlock new perspectives on self and the world. This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

That's pretty much how every treatment, for almost anything, should be.

Unfortunately, in most professional services (not just doctors), the people providing the service just have a few "recipes" on how to solve certain types of problems and then they just prescribe that. If your problem doesn't fall into any of their predefined categories, then good luck.

The typical interaction is: you have an initial session/interview where you describe your issue, then they immediately diagnose you (unless they require some additional info - documents/exams), and finally they provide their predefined solution. They never observe you in your daily routine to see what's actually going on, they don't study you to provide a personalized solution.

It's as if programmers would never debug a program, only get told by someone what the issue is and then they provide some library/api/piece of code that deals with what appears to be the issue from the outside.

> This absolutely has to be done by a trained professional with personal experience with the substance and who has assisted with other guided sessions. It's not going to be a prescription that a doctor can throw at the patient and then check up on in a few weeks time.

Seems like a bang-up business model, along with all sorts of other regular-meetings-with-the-professional therapies. Biologics on the pharm side, or just plain old therapy on the practitioner side.

Industry has plenty of practice with "every month or two" doses, so I wouldn't be so cynical in the attempts to remove the side effects. "Can you do it without getting high" is something that would greatly expand the audience and give people a better experience.

Ketamine is being used to good effect these days in major depression. I wonder if they ramp up the doses like that when using it?

They don't.

Fwiw, the psychedelic effect of ketamine is separate from its antidepressant effect.

Hm, could you elaborate on that please? Do you mean the separate as in stereoisomer-wise? Or do you mean that ketamin has multiple effects on the brain or central nervous system, and one is the antidepressant effect and the other is the tripping balls effect? (And obviously pharma would like to find out what's going on exactly in the first case or ... how to block the second case while still having the first effect happen?)

* the stereo-isomers have differing effects: s-ketamine being more inebriating and less anti-depressant, while r-ketamine is less inebriating and has a stronger anti-depressant effect.

* The inebriant effect can be modulated without altering the anti-depressant effect, at least in lab rats. Cannabis is one drug that does this.

* The pharmaceutical company that ran the clinical trials for esketamine likely did so because it is actually the least effective anti-depressant of the two entanomers, and less effective than regular ketamine. By trialing and patenting the less effective one first, they can then patent the more effective one later, and make money longer, by dragging their feet. Esketamine is currently a few hundred dollars a dose (every three days). My ketamine is $70 for ~6 week supply. Capitalism is wonderful.

* fwiw, ketamine triggers other pathways in the brain, including ones that are involved in attention deficit and wakefulness. It has the same effect as amantadine - an ADHD medication. I can't take it after 10 am or so, if I am going to get a decent night's sleep.

Off-label use is great, doctors love it, but ... trials don't show much.

" [...] esketamine’s results are at least as bad as any SSRI’s. If you look at Table 9 in the FDA report, ketamine did notably worse than most of the other antidepressants the FDA has approved recently – including vortioxetine, an SSRI-like medication."


See later on in the article:

> Another possibility is that everyone made a huge mistake in using left-handed ketamine, and it’s right-handed ketamine that holds the magic. Most previous research was done on a racemic mixture (an equal mix of left-handed and right-handed molecules), and at least one study suggests it was the right-handed ketamine that was driving the results. Pharma decided to pursue left-handed ketamine because it was known to have a stronger effect on NMDA receptors, but – surprise! – ketamine probably doesn’t work through NMDA after all.

Case isn't closed yet.

Hah! Serves them right.

I think pharma pursued left-handed ketamine because they could patent it and charge a king's ransom for it, whereas your dog's vet has a bottle of right-handed ketamine for $5.

Meditation has similar effects - some people will have a single mind-blowing experience and a lot of their problems go away at once. Others practice for years and slowly whittle away at the sharper corners of their mind.

The problem is, you may not know what type of person you are going to be till ten years in. I suspect the same is true of psychedelic dosing: some of those soccer moms may need a strong depersonalization experience to get any real benefit from it. In some psychonauts it's going to trigger psychosis. I'm glad there's finally research being done in this area, the possibilities are certainly very exciting.

"The problem is, you may not know what type of person you are going to be till ten years in."

Very true. I used to fancy myself a psychonaut, then i got careless with 5-meo-dmt. Now i'm a teetotaler. Upon reflection i can't say i ever really liked tripping.

That’s probably true some of the time, but I think there’s a mode of mental health issues that I’ve experienced personally and seen in others who approach life with one foot on the gas and one foot on the brake. Basically, my hypothesis is that some people have contradictory impulses of desire and fear of stimulation and calm at the same time. You don’t have two groups of people (novelty-seeking HN crew vs vanilla soccer moms), but one type of person who is both and in conflict with themselves.

That's me. Easily overstimulated, yet drive myself to exhaustion because everything is too damn exciting. If you ask me it's a combination of high dopamine and high neural excitability/high connectivity. I think many programmers are like this and exist in a semi-permanent state of exhaustion.

This is a bad assumption on both ends (HN comments are most definitely not a bastion of free thought and expression.) but If people affected by PTSD can re-experience their trauma in controlled therapeutic settings using psychedelic compounds, so to can most others. Psychedelics are not for everyone, but they are certainly also not limited to chosen ones.

As a mini-side rant, I've found that people in the psychedelic community (defined as those that purposefully use psychedelics vs more spur of the moment usage) have pumped them selves up on their own identities as these "open minded explorers". I've actually found them to be belligerently dug in when faced with new evidence, information, and perspectives.

Source: I helped run a major city psychedelic community for a couple years

I honestly don't understand what happens to some people they trip. When I trip I get torn apart and question everything I believe in. After my first trip I thought wow if only everyone could experience this people would open their minds.

Then in time I met more and more people who regularly use psychs who were stuck in dogma. Recently I saw an interview with Dennis McKenna of all people who regularly trips (like his brother) and he just came across really disconnected like a dogmatic liberal like he was repeating what he had been told rather than thinking for himself.

It's been bothering me for a long time trying to understand it. I think the conclusion I have come to so far is that it opens your mind but only above whatever baseline you came from. The other thing is because the experiences have a feeling of being profound people who are not that open minded end up worshiping it and just fit themselves into that niche.

There's a long rant here, but it'll be pages worth of text. The short of it is that the so called leaders of the community are often accidental, untrained, uneducated, and largely unchecked. They say the right things and every one coalesces around them even if it's unsubstantiated gibberish (Terrance was the master of this and a total nut to be honest). It is very reminiscent of political dogma and zealotry (lets not pretend this is just a "dogmatic liberal" thing). Not to mention the big money they're pulling in from it now too (looking at you Bill Richards.)

There's no reason to continually trip, to take large doses, to try multiple psychedelics, etc. It's up to the individual to decide on what feels right for them. It is one of the most subjective and personal experiences you can have. Benchmarking against others is just...destructive really. No one in the community is saying that right now. It's just spiraling group think.

Yes essentially the leaders become like religious leaders. The problem is there is usually a kernel of truth to what they are saying which makes it easy to buy into if you're not thinking critically about it.

> But it seems like most of the clinical research is going into micro-dosing: i.e. how to make this something you would take every day to alleviate symptoms. I just don't understand the benefit of this approach other than the fact that it might be a better business model.

Could be because it's supposedly quite prevalent in Silicon Valley, so it's a cheap way to study its effects in a largish population that's self-medicating. Research is expensive!

I think it might just be a hangover from the view that "you're missing X from what we consider a normal neuro-chemistry so we'll give you a constant dose of Y to make some changes to the level of X"

This has always felt like it was treating the wrong thing. The way that neurons operate seems to be much more complex than just the changes made by neurotransmitter levels and flooding the entire network with higher levels of a neurotransmitter probably has all kinds of unintended consequences. I think this approach is often applied because its something that can be done quickly and easily and has immediate effect rather than spending months and years retraining the patient's brain. I hope that we see a revolution in clinical treatment that combines guided psychedelic therapy and daily practice. We need a more compassionate approach than just twisting a knob and nailing it in place.

this may not be entirely what you were getting at, but for the "daily pill" vs. "once a month" or "once every 6 months" - the business models already have precedents for this - there are psychiatric, migraine, autoimmune disease, and oncological drugs that are dosed monthly, every 3 months, every 6 months etc.

Unless I'm misunderstanding you completely, what's wrong with that idea? Currently, anti-depressants are a very hit and miss science, leaving many people further frustrated by therapy that was supposed to help them instead. Anything that can move towards better medicine in the future should be a good thing, no?

What's wrong is psychedelics already work as-is, but due to stigma around "fun" alterations of consciousness possibly being beneficial (along with desire for a patentable compound that can get through FDA regs), most of the focus has been on how we can go about removing the wetness from water while preserving water's essential useful properties. Regardless of how many years go by and self-reporting along with scientific evidence accumulates that water's wetness is mostly the entire point, and all while people are being thrown in jail for water possession.

I agree with your statement on principle that we should make these drugs widely available when we find efficacy.

I disagree that we shouldn't try to separate psychedelic effects from therapeutic action. There is a body of research on ketamine metabolites. Some of these metabolites may have less psychedelic effects and more anti-depressant action.

I need to take ketamine almost every day. This means there are several hours when my ability to read, think, and remember things is impaired. I hope we are able to discover better drugs.

> This means there are several hours when my ability to read, think, and remember things is impaired. I hope we are able to discover better drugs.

I don't think people give this enough consideration. Tripping on mushrooms might be enjoyable to some, but having it as a regimented treatment means you are losing a lot of time where you cannot be productive, cannot enjoy the company of your sober friends and family, etc.

The psychedelic effect IS the therapeutic action.

> What's wrong is psychedelics already work as-is

The current research into psychedelic medicine is better described as intense therapy with a psychedelic adjunct for some sessions.

They aren't just giving people psychedelics and hoping everything turns out okay. The psychedelic dosing is combined with therapy, and the sessions are both preceded by and followed with additional therapy without psychedelics.

It's a mistake to assume that the psychedelic drugs are curing depression on their own. In fact, many people experience worsening depression or derealization if they take psychedelics without professional guidance while suffering from mental illness.

> They aren't just giving people psychedelics and hoping everything turns out okay. The psychedelic dosing is combined with therapy, and the sessions are both preceded by and followed with additional therapy without psychedelics.

And historically, that's exactly the way psychedelics have been used, for thousands of years. A shaman/guide would provide the medicine and help the people go through the experience, usually in a tight community where there's follow up and support.

Unfortunately that was suppressed, first by the Catholic Church when the Spanish arrived to America, and now more recently by making psychedelics illegal.

The idea of psychedelics being some sort of party drug is a problem of the current state of affairs, politically and culturally, where we have abandoned or forgotten their origins.

Maybe just the "tight community where there's follow up and support" may help.

It's not "stigma". People treated from clinical depression hope to be able to function in their normal day lives at work and at home, not just be on a never-ending psychedelic trip.

This is exactly the stigma psychedelic enthusiasts have in mind. Psychedelic-assisted therapy doesn't need to rely on patients being administered psychedelic doses on a daily basis.

What's actually happening (either in trials or by underground practictioners) is that the super-malleable/open to self-analysis mental states that can be induced by psychedelics can be a catalyst for significant long-term shifts in perspectives and thinking patterns.

An amazing book to give you a cursory understanding of the state of the field is How to Change Your Mind: The New Science of Psychedelics by Michael Pollan. It'll give you a good understanding of what psychedelic research may be able to achieve (and what it's achieved so far).

> This is exactly the stigma psychedelic enthusiasts have in mind. Psychedelic-assisted therapy doesn't need to rely on patients being administered psychedelic doses on a daily basis.

Why does it have to include the psychedelic component though (even sub-trip-levels)? Some seem to think that you absolutely must not divide the psychedelic qualities from other qualities, even if you could. As if "you only deserve to enjoy the anti-depressant benefits if you embrace the trippy potential of it". That sounds too religious to me.

I find that a weird stance, and I'm very pro-psychedelics and would like to see them regulated but legally available. But I wouldn't want to keep depressed people who are afraid of the psychedelic experience from the benefits just because it won't help with legalization efforts.

Again, I'm not suggesting that you can split them into "trip drug" and "anti-depressant drug". But if you could, I'm absolutely for doing so. I'll still take the trip drug, but people who are afraid of tripping can take the safe one and still get benefits.

I believe the sentiment most people are expressing when they say you cannot separate the "trip" from the beneficial effects is that they both have the same origin or causative agent. Personally I'm in the "neural annealing" camp and it makes sense to me from personal experience that the benefits are due to psychedelics being a drug that essentially induces a state that you would normally only experience during profound and meaningful experiences. Those are the only other circumstances where I have felt the same as I have with psychedelics, experiencing a deep connection with the awesome scale and complexity of the natural world, falling in love, reading a life changing book, being transported emotionally and mentally by a symphony, getting caught up in the experience of a great movie, the physical rush of pushing yourself to your limits when exercising. We have drugs that seem to be able to produce the same life altering experiences that they can on demand. That's why it seems perverse to many people when it's argued that we should distill just the dregs of chemicals that produce the change without realizing that the actual mental and physical journey, the story that you weave around that experience that includes yourself, your thoughts, your environment and the people around you is probably the most important part. You can't just be happy all the time without having a reason to be happy, you can't be in love without someone to love and if you could it would seem more like a nightmare than an improvement.

I completely agree that the profound experiences you can have during psychedelic trips can be life-altering. I don't know whether it's the experience that leads to the other benefits, and if it doesn't, I see no reason why one would have to get them bundled.

The OP's comment reminded me of a some people I've come across that were into meditation and were anti-psychedelics, and to me it seemed like their main issue was that you could get these very deep experiences like ego-death but you didn't earn it, you didn't sit and quiet yourself for months and years, you just popped something into your mouth, experienced a bit of nausea and were teleported into a different dimension. It always seemed to me that they felt cheated because they took the hard road and felt that it's unfair that others took a short cut. Needless to say that it was even weirder given that they also tend to talk about compassion and inner peace a lot.

I totally understand if you believe that you simply cannot separate the psychedelic from other parts because it is what gives the benefits. I did get the feeling that that's not quite it though, that there's a lot of "and you shouldn't try to", and that feels like "you shouldn't get the benefits without embracing the experience, potentially encountering your demons etc", or a religious practice surrounding it.

>> You can't just be happy all the time without having a reason to be happy, you can't be in love without someone to love and if you could it would seem more like a nightmare than an improvement.

What you are describing is the state of enlightenment, and those who have had sustained experiences with it would disagree.

it's hard to argue with a buddha I guess

> I believe the sentiment most people are expressing when they say you cannot separate the "trip" from the beneficial effects is that they both have the same origin or causative agent.

Perhaps I've swallowed too much propaganda, but this seems like a testable belief. What if it's not true? What if psychadelic-assisted therapy is just one of multiple viable psychadelic-assisted treatment approaches? What if people want to be able to use store-bought neurotransmitters to regulate their minds without going through the trip-induced emotional or spiritual experience that they may not want?

Would achieving a deeper understanding of the relevant neurochemistry and allowing people to make their own choices be so bad? Would more treatment options be a negative?

I don't oppose the research or having more treatment options, I'm sure they would be necessary in many cases. My perception of it is a bit negative though at least when imagined to be an easy to access option for everyone, it's the same sort of opposition I feel towards the idea of taking steroids to promote muscle growth.

the psychedelic effect is simply (so to speak) the outcome of shutting down your executive function (that one that creates your internal monologue and gives you the perception of the self) so that the rest of your brain function that normally are "kept together and normalized" become more accessible for analysis and introspection.

Psychedelics are not anti-depressant, are just a potent accelerator for discovering WHY you're depressed. The psychedelic experience is necessary to the therapy. If you ever did a dose once you would understand exactly what I'm talking about, it's pretty hard not to understand what's happening once you experience it, just as it is essentially impossible before doing it.

> If you ever did a dose once you would understand exactly what I'm talking about, it's pretty hard not to understand what's happening once you experience it, just as it is essentially impossible before doing it.

Sorry, that sounds religious. I've experimented with psychedelics quite a bit, I've had very different intense experiences on them that have strongly affected me for long periods of time. That said, psychedelics do not unveil truths to you, not about the universe, not about yourself, but it can absolutely feel like it. You don't discover "why" you're depressed (as if there was a why, and understanding it would magically take the weight off of your shoulders; it's not a Hollywood movie).

That's just mysticism and naive religious interpretation imho.

You understood very little of what I was saying and it looks on purpose. If you like to go around feeling morally superior to people of faith (I’m not one of them btw) then leave me out of that please.

This is not how psychedelics for treatment resistant depression is tested. The most common treatment protocol is a single psychedelics session assisted by 2 therapists (preceded by a few therapy sessions and some follow-ups). Overwhelmingly the evidence point to very significant effects lasting months after the session.

This is far from "a never-ending psychedelic trip". If you follow the evidence for the most researched treatment protocol, this would involve a session every year or half-year.

> The most common treatment protocol is a single psychedelics session assisted by 2 therapists (preceded by a few therapy sessions and some follow-ups).

Ketamine is approved by the FDA for depression and also has a history, albeit shady, of being prescribed off-label at IV clinics. This is far more common than psychotherapy while taking medication and much less expensive too.

> If you follow the evidence for the most researched treatment protocol, this would involve a session every year or half-year.

In this small survey 60% of patients returned once a month or more for maintenance infusions.

A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders https://pubmed.ncbi.nlm.nih.gov/28669202

Psychotherapy is seen as prohibitively expensive because of the way it is currently practiced where the patient must see the therapist on an ongoing basis. This isn't necessarily a bad thing, it's a lot like seeing a personal trainer on a regular basis but it's certainly an expensive way to stay fit. Psychedelic therapy seems to be an option that helps make a much smaller number of sessions "stick". If you only have to do 3 sessions a year then it means the therapists can see a much larger number of patients and the overall cost for each patient could go down.

My opinion is that most people could handle (small) group therapy as well which could further reduce cost and might actually have a number of benefits for those involved.

FWIW, Ketamine is not a psychedelic. It's a dissociative.

It doesn’t affect the same receptors as “classic” psychedelics (LSD, DMT, Mescaline) but dissociatives aka dissociative psychedelics are wildly psychedelic at high doses. It seems ludicrous to insist otherwise. Is Salvinorin-A not a psychedelic?

I have a prescription and take it every three days. A clinically effective intranasal dose is about as psychedelic as a couple of beers.

I think you have it a little backwards. IME, psychedelics give dissociative effects along with the psychedelic experience and the dissociative experience is solely dissociative on its own.

I think there's a lot of confusion on what a psychedelic experience is and it gets confused with a hallucinogenic experience, which both classes of substance can offer.

I’ve been following this stuff since the mid 90s and am familiar with the terminology.

What do you assert is the difference between a psychedelic experience and a hallucinogenic experience then? Dissociative I agree only partially overlaps with psychedelic on a venn diagram but hallucinogen and psychedelic I understand as synonymous.

Hallucinations are pretty concretely defined, medically. Seeing stuff that isn't there. Hearing stuff that isn't there. Things moving when they aren't.

For me, the psychedelic experience is more about the "Ah hah! we're all in this together! We're all the same thing! I've removed the veil and barriers I've built up all my life and can finally see clearly what it's All About." I'm sure it's different for others, but I don't experience that "oneness" or "connection" on dissociative. It feels like I am born again, free to be vulnerable and experience the world without the lenses that society and myself have placed over my eyes.

I think the term there is "entheogenic" a la DMT:


Research has focused on long-term (months to years/permanent) benefits from just one or a small handful of psychedelic experiences. It would even be difficult to find marginally responsible "psychonauts" who would recommend attempting a "never-ending psychedelic trip", which regardless wouldn't be physically plausible due to how rapidly the short-term tolerance increases.

In short, perhaps do more research on this topic because you're arguing against a position no one has taken.

"Life is the never-ending psychedelic trip, maaaan"

On a serious note, this isn't what GP is referring to. Generally psychedelics in the work day are self-limiting. A microdose that is more of a mesodose makes for some interesting Zoom meetings. People learn the right dose to get a boost without excess distraction/warping. Fadiman's research [0] suggests the best dose is well below the threshold of "trip" effects. So there's no risk of never-ending daytrips, unless one desires that thing. So why limit access?

Aspects of American culture have a strong stigma against "fun", euphoria, and to an extent, any effect beyond "restoring normal". eg nootropics are popular in young, hip crowds like HN, but kinda sketch among many MDs, from "I don't think these are safe" to "why do you need that?" It's a "if it feels good, stop" sentiment that runs as an undercurrent through American history and you can see signs of it in Protestant work ethic, Prohibition (of alcohol and cannabis), and of course the war on drugs.

Keep in mind, LSD and MDMA were very hotly researched back in the day, but when subcultures started associating them with parties, that's when things started getting the kabash.

"But addiction bad" - this would be a fair argument if it weren't for the near lack of correlation between DEA schedule and addiction potential [1], as well as the rapid action to ban analog drugs without any consideration to addiction potential. This is the fate of most Shulgin compounds, many exhibiting the typical rapid tolerance of psychedelics.

That leaves the theraputic dose. These are typically administered in a guided setting, either in the clinical sense, or trip-sitters/sherpas, in the informal. This is the best mitigation against trips that leave lasting psychological harm (the term "bad trip" is very loaded, as it doesn't distinct "hard lesson trips" from "no this actually messed them up long term"). If the concern is really "harm trips", then the solution is logically harm-reduction, not prohibition.

Wew, that turned out longer than expected.

Edit: added more

[0] - https://www.thecut.com/2018/05/microdosing-guide-and-explain...

[1] pdf - http://citeseerx.ist.psu.edu/viewdoc/download?doi=

If you take an anti-depressant pill everyday and it solves your problem, why is that bad? Are you hostile to medication in general?

Daily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips. It can be expensive. It can stop working, from tolerance. It can have unpleasant side effects.

A one-time, permanent cure is clearly superior. And your closing sentence was unnecessarily combative.

> A one-time, permanent cure is clearly superior.

No research points to psychedelics being a one-time, permanent cure. That's an extreme misrepresentation of the science.

In fact, the current psychedelic research revolves around a series of intense therapy sessions, a small number of which involve psychedelics. They aren't just giving people psychedelics to take at home and hoping for the best.

And again, no serious researchers are suggesting that depression is cured permanently, let alone with a single ad-hoc dose. This should be common sense, as many people who used psychedelics recreationally still suffer from depression. Indeed, psychedelics can worsen depression for some people.

Properly replicating these psychedelic-assisted therapy sequences is going to be expensive. I'm sure the vast majority of people would prefer a daily pill that has no cognitive distortions.

I never suggested that the dose be ad-hoc, nor implied that we should just give people psychedelics to take home and hope for the best.

"One time cure" is indeed not accurate, today, but as a shorthand it captures the promise of psychedelic treatments. A single session can give benefits lasting many months, and some people may remit entirely. This is why more research is needed.

>I'm sure the vast majority of people would prefer a daily pill that has no cognitive distortions.

These don't exist. Existing psychological medication, not unsurprisingly, often comes with severe cognitive distortions - far worse than a single psychedelic trip every few months.

Psychedelic trips aren't a permanent cure for depression though. They have really good long-term effects on remission, but that still means nearly half won't remit.

> At a follow-up appointment after three months, 5 out of 12 patients were still in remission and 7 out of 12 showed a continued response

It often shines a light on the causes, but sometimes the causes are intractable/ongoing, or the only resolution is to learn to accept.

[1] https://tidsskriftet.no/en/2018/11/oversiktsartikkel/psyched...

> A one-time, permanent cure is clearly superior. And your closing sentence was unnecessarily combative.

So if we don't have a one-time, permanent cure, we shouldn't try to get a daily medication? Because ... why exactly?

>Daily medication, which must be taken without fail in order to have a normal life, is a liability. It can be lost, stolen, or missed. It must be obtained on a regular basis, and carried around on trips.

I doubt these are a real problem for people who have a modicum of conscientiousness.

>A one-time, permanent cure is clearly superior

If you think that big bad pharma companies are keeping people from taking one-time cures for depression, by all means come up with a one-time cure on your own. How do you think one pill can create a permanent structural change in the brain that makes the just-so changes necessary to cure depression forever?

> I doubt these are a real problem for people who have a modicum of conscientiousness.

What does conscientiousness have to do with it?

You might need to travel or transit through a country which prohibits carrying them. Now you have to cancel the trip or go without the medicine.

> by all means come up with a one-time cure on your own

This is not helpful. People have the right to ask questions without being asked to devote a lifetime to develop some arbitrary authority (which would then in any case bias them to look for positive results).

Are there any examples of medication other than ADHD medication that are have such restrictions in certain countries?

Yes. You need to get permission to take a vast number of medications into UAE, including opioids and even common antidepressants.

I went through this process before COVID, with the intention of travelling to Dubai, and they knocked back my request about 10 times for spurious reasons, and were adament that I couldn't enter Dubai with a single pill more than was required for the duration of my time in Dubai. Which of course is completely unrealistic - I'd need some for travelling back, and a small buffer because of flight delays or whatever.

Honestly, travelling with certain medications is a major PITA.

Opioid-based painkillers for sure, sleeping pills, apparently even decongestants like Sudafed because they contain pseudoephedrine.

The point I was making is that right now a one-time cure seems impossible. If you think it's doable, please come up with some evidence for it.

Please have your strawman back as I said nothing about the feasibility of a one-time cure. I was backing up dTal's right to say that a one-time cure would be superior, without suffering a pointless ad-hominem rejoinder that why don't they find one if they're so clever.

One-time cures may be a sci-fi dream but they are highly desirable, as anyone who needs regular/prophylactic treatment for any severe ongoing condition knows.

> Now you have to cancel the trip or go without the medicine.

International travel is a minuscule thing to give up if you get effective depression (or pretty much any chronic condition) treatment in exchange. Heck most people can't justify the expense of international travel in the first place and the number of people who do it regularly for work and have depression is very small compared to the number of people who have depression. Practically nobody is going to let a chronic condition that affects their daily life go untreated because there's a short list of countries they can't have that treatment in.

What exactly are you arguing? That people should be happy with the flaws of the status quo, and that we should not follow up on promising new treatments that don't have those flaws, because...?

I thought my point was fairly clear and I'm not sure how you managed to derive the "people should be happy with the status quo and not follow up on promising new treatments with less flaws" from what I said. I'm arguing that "prevents international travel in some cases" is an inconsequential side effect for anything that treats an often debilitating chronic illness that is not even within the realm of consideration for the overwhelming majority of patients and that likewise "no negative effects on international travel" is not really a meaningful improvement over the status quo of treatments (all else being equal). Basically, if your biggest gripe with a treatment for a chronic illness is that you can't travel internationally then that's a pretty small gripe.

It was one example to illustrate one of the potential problems.

A much bigger issue is as pointed out by harimau777: prescriptions often don't get filled on time and sometimes not at all. Plenty of people run out of pills on holidays and have to suffer withdrawals, with suicidal ideation and actions being one of the symptoms of acute withdrawal from benzos.

Daily medication that requires a prescription is a huge problem for people that actually have to take it. What if they can't afford it at some point? What if their physician changes and the new physician doesn't want to prescribe it?

Why are we even defending daily medication? If there is any possibility of a permanent cure, obviously that is a much better choice of treatment.

His biggest gripe is that the pill has to be taken every day or very frequently. There are loads of circumstances which make that less desireable than taking a pill a few times a year instead. You've latched onto the travel example he gave.

> I doubt these are a real problem for people who [have good mental health]

Yeah. Funny thing about that. You're generally prescribed as low of a dose as is feasible, so by the time you're due to take your ADHD meds, antidepressants, antipsychotics, or whathaveyou, the last dose has worn off (especially first thing in the morning) and you're liable to miss a dose. So you get a pill minder, and fill it weekly, so at least you can check to make sure you don't forget and double-dose yourself. Chances are, you're taking several meds, so you have a highly detail-oriented chore you need to succeed at once a week on a specific day. If that's a bad day, you might not be able to muster the motivation and that throws off the whole week. Or you get most of the pills in but accidentally miss a day or a whole week's worth of a drug because you're juggling a handful of bottles and you're only human. Phone apps sound great, but depend on you being near your pills and your (charged) phone at a specific time of day, which has all sorts of failure modes.

And then there's the uncontrollable shit. You pack for a trip out of town. You're only supposed to be gone for a week, so you diligently pack a week's meds. Your ride home flakes, flight gets cancelled or whatever, and suddenly you're S.O.L. Or, your bag gets rifled by luggage inspectors at the airport and they pocket the goods (I've lost a nice pocket knife that way), it's stolen by hotel cleaning staff, pickpockets, or whatever. Good luck getting your prescription filled in a different country.

And once you miss a pill, you might hit a spiral that lasts a week or longer before you get back on track. It's a fucking liability.

At least for controlled substances, it is definitely not that simple. Patients can run into situations where pharmacies refuse to tell them if they are able to fill a prescription until it is actually written for them. However, if they are not able to fill it, the doctor is hesitant to write a new prescription for a different pharmacy because it could look like they are writing the patient multiple prescriptions for the same drug.

> How do you think one pill can create a permanent structural change in the brain that makes the just-so changes necessary to cure depression forever?

From the article: "...clinical trials with psychedelic drugs suggest long-term anxiety relief in patients..."

I'm not really sure what the context of your comments is, if you're not aware that this is what the entire thread is about.

I found myself irritated enough to talk about conscientiousness.

I have a permanent medical condition which calls for a somewhat antique medication. It is typically used "as needed," certainly not every day. I have had a regular prescription for over a decade and it has certainly improved my quality of life. I refill like clockwork, I am responsible about using it. It comes time for a refill and ... my pharmacist at Walgreens regrets to inform me that they cannot seem to get it, and that the manufacturer has stopped making it.

This is worrisome. I remember life before the medication. I dig through the FDA databases, locating every organization which has applied to make the medication and been issued an NDC (National Drug Code) identifier. Each organization is tracked down: are they still in existence? Have they been bought out and if so, by what other company? I discover buyouts, shutdowns, press releases saying that they are "exiting" some market. I make phone calls, I send emails, and, when no other contact information is available, I send letters with self-addressed stamped envelopes. Almost everyone who has ever made it has stopped or been stopped in one fashion or another. Meanwhile, I begin to canvass the distributors: McKeeson, Cardinal, AmeriSourceBergen. Are there any remaining in stock? If so, which pharmacies in my area do they work with? Most pharmacies have a single distributor. These are organizations who do not like to be contacted by the hoi polloi, and I have quite a lot of "How did you get this number?" conversations.

At last, a hit: someone has just started manufacturing it. Out of all of them, there's only one. I dutifully take this to Walgreens. After a few go-rounds, they cannot seem to get ahold of it. They suggest Walmart. I have to hassle my poor doctor's office, now in COVID-panic like everyone else, to move my script, which one required a special paper. Walmart swears they have it, they have contacted their distributor, they have bottles in stock. Wonderful. And it does not arrive, they call again, and it does not arrive, and they call again. Finally, they shrug and give up. Right!

I call CVS; they are sure they can get it. I transfer the script, again. Off I go to CVS. CVS says that, yes, it is in stock at their distributor. Similar to Walmart, after a few weeks, they cannot get it. The pharmacist has called the corporate offices and only knows that there is a "corporate block" on it and that, despite being able to submit an order for a bottle of pills which are present at a distributor, they will never ever arrive. I am disappointed, and, out of a little curiosity, I submit a letter to CVS corporate (again with the self-addressed stamped envelope to remove barriers to reply) asking just what this block is ... not that I ever get a reply.

I try a small, local shop. I wince at having to call my doctor to have the script transferred yet again. Surely they will try harder rather than giving me the brush-off you can so often get from large organizations. No dice. The dance is now familiar to me.

Armed with yet more research and NDC codes and distributor phone numbers, I approach my original pharmacy again. Another script transfer, with all of the pain entertained in moving something with a low Schedule number around. With the new information I have gathered and a great deal of persistence, they manage to obtain it. The head pharmacist tells me that the sole other patient on it will be relieved, and that he has never had to work this hard to get a prescription before.

By the end of this two month period, I had lost approximately twenty pounds and was clumsily knocking things over due to my coordination degrading. Finally, I managed to fall hard enough that I was still limping two months later.

The moral of the story is this: being conscientious does not guarantee availability. One can do all of the right things and still not have it on hand. Being dependent on a medication, even weekly, can be a burden, even if you attend to the situation quite closely. I urge you not to be quite so flippant about it.

>modicum of conscientiousness.

Is that common in people suffering from mental ill health?

>I doubt these are a real problem for people who have a modicum of conscientiousness.

How insensitive of you.

Most people I've met who solved their problem in this way seemed, as a side-effect, to have distorted their personalities in noticeable ways. (I am not claiming that this tradeoff is never worth it, but something rarely considered, and usually not noticed by the person taking the medication.)

To be more specific in the kind of distortion I noticed: lack of empathy, shorter attention span, lowered curiosity.

I would say if the symptoms reappear when you stop taking a medication, your problem isn't solved so much as the symptoms are being managed. Given that mood disorders can be due to some underlying conflict within the person's psyche, simply alleviating all negative symptoms seems at odds with the goal of getting as many people as possible to self-actualization.

"Given that mood disorders can be due to some underlying conflict" - that is an interesting assumption. It is one of those things that is impossible to prove or disprove. My position is most complex organ systems have biological abnormalities that are prone to dysfunction, such as diabetes, albinoism, genetic predisposition to heart disease and cancers, I'm not sure why the brain would be different in that regard.

Assuming there is an underlying conflict driving things, then medication might be simply masking the symptoms, which is a perfectly valid approach in dire situations, no use seeking out the underlying conflict if the symptoms kill you before you come to a conclusion.

However, if there is no underlying conflict and this is just a twist of fate, searching for an underlying conflict can be aggravating and misleading. If waves of negative emotion occur randomly (or semi-randomly), as has been my experience, and you assume there is always some valid reason for these feelings, the tendency is to re-arrange your life searching for a solution, if that solution does not exist because there is no underlying problem, constant rearrangement can blow up your support system and the routines that help maintain your daily living.

I did say 'can be'. The soldiers with PTSD whose depression has improved with small numbers of treatments did not simply suffer from a biological abnormality - their brains changed in response to stimulus, which is after all what we'd expect brains to do.

I do think brains should be viewed as different from most organs when we describe medical intervention, they are plastic to a degree other organs are not. If a diabetic could simply 'mutate' their pancreas to function normally with a single intervention, I think most would prefer that to taking insulin all their lives, even if the one intervention was distressing.

Brains actually can change in very dramatic ways. Most are for the worse of course, and we instinctively avoid any change in our mentality, but they are times when it is actually preferable.

>Given that mood disorders can be due to some underlying conflict within the person's psyche

Couldn't be further from the truth. I know where you're going with this and I think we are in agreement on the majority of mental illnesses (as the brain's best response to stress), but mood disorders are in a different category entirely. Mood disorders and schizophrenia do not respond to therapy. They are never cured or recovered from. All you can do is manage the symptoms.

I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.

> I take a prescribed ketamine lozenge every day. I don't experience any psychedelic effects and I'm fine with that.

Many of the researchers and clinics are gravitating toward ketamine regimens that avoid hallucinations entirely, like your current treatment regimen.

Ketamine has some inherent anti-depressant effects that don't depend on hallucinating. Unfortunately, many psychedelic proponents have tried to push the narrative in the opposite direction to emphasize the trip.

It's unrealistic to expect depressed people to routinely go on psychedelic trips to keep their depression at bay. It's also unrealistic to expect people to trip frequently and not have part of the population start to accumulate weird, irrational ideas from their trips.

A medicine that captures the anti-depressant effects without causing a psychedelic trip or really any cognitive distortions at all would be far better than expecting people to trip regularly. I don't understand the aversion to pharmaceutical companies pushing the research in this direction.

I’m very curious about how much you take daily and the effects. I’ve read about the super high dosage therapy, and that made a lot of sense to me. Are you just ever so slightly dissociated at all times?

Not the OP, but I'm prescribed ketamine for chronic nerve pain.

Prescription is for 25mg orally 4-6 times a day, but I find 15mg as effective as 25mg, but with no side effects at all.

At 25mg I do feel slightly dizzy for an hour or so.

Ketamine has a small, but noticeable effect on the pain - but has had a huge effect on my ability to deal with the pain.

I dunno about them but, but I get by on 20mg taken weekly. If I miss a dose, it's usually ok. If I miss two, suicidal ideation is my dominant thought pattern. As for effects, I'm a little dizzy for about 30 minutes and I prefer to spend this time napping or in a hot bath.

All medications have two kinds of effects: therapeutic effects, and any number of side effects.

The "problem" with compounds that can alter our state of mind is that, by definition, they can be fun/weird/recreational if taken in meaningful doses. And this, of course, scares the government and the pharmaceutical industry. They are not allowed to sell things which can be used for disorder (read: "recreation").

So the pharma industry must select against these compounds. What we're left with is medication where the active, psychoactive effect is so small that it's of the same magnitude as the side effects. This prevents "abuse".

Hence why antidepressants are basically constipation/headache/libido killing pills that kinda maybe change your frame of mind.

> And this, of course, is what scares the government and the pharmaceutical industry.

The opioid epidemic has shown that not all pharmaceutical companies feel constrained in this way.

This is an excellent point and seems to torpedo my entire argument.

Why are you hoping for that? Is non-hallucinogenic anti-depressant a bad thing in some way?

The profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely. Psychedelic research up to now is pointing to small numbers of uses having lasting positive effects. There is a fear that research driven by a profit motive will try to not just not investigate this further but actively gloss over this potential medicine.

> The profit motive would clearly prioritize finding an expensive medication that must be taken regularly and indefinitely.

The idea that pharmaceutical companies are deliberately avoiding one-time treatments is a myth.

If you assume profit is the ultimate motive, there's nothing stopping a pharmaceutical company from charging $10,000 for a long-lasting depression treatment.

It's not like pharmaceutical companies are going to stumble upon a perfect treatment and then decline to patent it.

Also, patents don't last forever. Common SSRI anti-depressants are available for $4-5/month.

Everyone I've known who took such medication have altered their personalities in noticeable (unpleasant) ways. It may be worth it for the person in question, but one should be aware of it.

Maybe I’m too self involved, but I’ve never noticed someone microdosing psychedelics til they have told me

Selection bias. Plenty of people take SSRIs with positive experience.

They're just not advertising it to the world. People who have bad experiences are much, much more likely to communicate this to other people.

This may be true, but even in the cases that I mention the experience of those taking the medication was positive, it is just other people who noticed the shift in personality.

that's not how it works. The anti-depressant, anti-addiction effect can only be achieved through the psychedelic effect since ego dissolution IS what you experience. Through that effect, you get to analyze the "parts" of your psyche without the executive function hiding the discrete parts and that's integral to WHY a psychedelic drug helps with those issues.

I don't believe this will ever be a once a week treatment.

Totally anecdotal but LSD made my depression significantly worse than improving it in any way. I had two proper trips and had a seizure kind of thing at the start of the second one due to the overwhelming visuals (not experienced anything like that before or since).

EDIT: to expand, it made me very questioning of my own consciousness and gave me severe and persistent existential dread and fear of death to the point where I felt quite suicidal (which I've _never_ experienced before). I restarted my old anti-depressants which have helped quite a lot but I don't think these feelings will ever truly disappear. Quite honestly it is the one drug I truly regret taking. If you aren't ready to accept what these drugs will show you then it can be a long-lasting and damaging experience, certainly it was for me

Thanks for sharing, I'd like to add my own experience on LSD and the long-lasting effect of fear-of-death it can result in. I have taken LSD only three times and can't say I enjoyed it very much, but I still wanted to give it a chance. Last time I took a 1/2 of what was recommended for me to see how it goes, and the beginning was pretty enjoyable, I played League of Legends, and the mobs started walking on the wall behind the monitor as if the view was projected on it, it was fun. I used to smoke a lot of weed at that time, and it always had a soothing and calming effect for me - not this time.

Marijuana never caused me any panic, but at the end of the trip, I was barely feeling anything and smoked a joint, what happened next was frightening. I felt an ache at my heart and considered calling the hospital for several hours, but was scared because of intoxication. I could not relax and sit at one place, there was darkening in my eyes, and peripheral vision was gone, and LSD made the feeling of fear massively intense. It felt as if my heart was going to stop just because I was thinking so much that I was dying.

I can only name what helped me then: I started walking short distances telling myself that if I manage to go from point A to point B then I'm fine and it's just a bad drug tripped. It helped, also tasting various flavours and hearing sounds from outside the street helped me focus my attention on something else. After a few hours of walking/tasting/hearing, I noticed my heart pace slowing down and the realisation that I wasn't in any real danger followed next. A terrible feeling that I will never forget. The bad trip lasted about 6 hours, and for the next few days, I felt a sharp pain in my chest.

sounds like your trip was done very sub-optimally. I can't imagine a violent video game being something I would like to be involved while on psilocybin or similar.

read this before trying again: https://en.wikipedia.org/wiki/Set_and_setting

League of Legends is hardly a "violent video game"

what? you're literally destroying a city and killing hundreds of creatures a game with the goal of destroying the building that allows them to exist. How is that not violent?

As others have noted, set & setting are hugely important as well as staying away from other intoxicants during the experience (unless you are experienced with LSD or in the care of someone to guide you through the trip). It's not surprising that the combination of the video game and weed would have this effect. I personally can't even look at a screen during a trip, it looks too cartoonish and just beyond uninteresting to me.

My personal rules for any LSD trip are: be in the company of others you feel comfortable being sober with (as in no drugs, not even weed or alcohol), be in a safe place or near a safe place you can get back to without much issue if things get overwhelming, relaxing music, lots of fresh fruit on hand. Oh, and make sure anyone you're with is not on any sort of anti-depressant. I've seen some bad mixes with SSRIs and psychedelics (primarily DMT).

You should be ready to go introspective during your trip. If things get overwhelming, lay down, focus on your breath, and remember you're tripping and that you will sober up in a few hours. Let yourself cry if you need to. The worst experiences come when you try to fight it.

My experiences with psychedelics and cannabis (many decades ago now) were similar in that LSD or psilocybin were terrific on their own, but the addition of cannabis made it extremely unpleasant. I still find cannabis unpleasant now. I found cannabis very enjoyable before trying that combination. My advice for any explorers would be to not smoke cannabis while tripping.

I've heard so many anecdotes about how to steer acid trips by mixing with other drugs.

These candy flipping practices seem like a great way to die!

The process that patients go through when participating in a medical trial of psilocybin is so different than the typical recreational setting that the rest of us experience these drugs. They do everything they can to make sure the patient is well prepared and has the minimum chance of having a bad trip.

However, every time I read about studies into psychedelics, I only ever hear about the upsides and not the potential downsides. I went through a similar experience to you - although not as severe. I had anxiety for about 3 years after my bad trip which luckily gradually reduced over time.

What worries me is that the more these drugs gain credibility in the medical field the more likely it is that depressed kids are going to self-medicate and given the ability of these drugs to multiply the user's existing anxieties, they should be the last people who should be experimenting and self-medicating with them.

> The process that patients go through when participating in a medical trial of psilocybin is so different than the typical recreational setting that the rest of us experience these drugs. They do everything they can to make sure the patient is well prepared and has the minimum chance of having a bad trip.

Not just this, but they surround the sessions with intense therapy.

They're not just giving people psychedelics and keeping them calm. Look up the MAPS (a foundation for psychedelic research) protocol. People are given a series of intense therapy sessions, only some of which involve psychedelics.

Sadly, many of the studies fail to have an active control group. That is, they aren't comparing therapy + psychedelics to therapy alone. That's a major pitfall in the current research.

And unfortunately, the therapy component of the research is lost in most internet headlines and articles. People are walking away with the impression that psychedelics are inherently anti-depressant compounds, when the reality is that they're being researched as adjuncts to intense therapy.

I also had severe, lasting anxiety after a couple of bad trips. I will never use again unless I get the opportunity to do so in a therapeutic setting with trained professionals. There is tremendous potential for good with these substances, but they have some real risks.

That's rough. I'm sorry you're struggling with the aftermath.

My own story may be relevant to you. FWIW:

I was really into zen as a kid. Part of my rebellion against Christianity and leaving my church. Once while meditating, I accidentally had a pretty bad trip. (I can describe the actual trip separately.) I was completely unprepared, didn't even know such a thing was possible.

It's kicked my ass ever since.

From what I read (afterwards), others have called that kind of trip ego death, death-rebirth, religious experience.

In buddhist terms, if that was the 2nd stage, I had ZERO interest in experiencing the 3rd stage, much less the 4th stage (aka "enlightenment").

A few months later, I was diagnosed with an acute life threatening disease. I was hospitalized for months, spent a few years recovering.

So the upside to having the living shit scared out of me while meditating was that actual near death real experiences were emotional cake walks. My care providers were like "Who is this kid?!" My family was less amused by my apparent blasé attitude.

Any way. To wrap this up.

We're all going get "there" one way or another. You're gonna die. It's all pointless. Yadda, yadda.

But you can choose to resume your normal life. You cope. You adapt. Fake it, if you have to, like I did. And eventually the habit of day to day living, striving, struggling, smelling the roses will become your new normal. Most of the time.

Just one caveat. Your pharmacology can absolutely change your brain, personality, outlook. Mental well being isn't just happy self-talk. Mind and body are inseparable. So figure out that other stuff too, if needed.

Honestly it was similar for me. I'm not sure if this is related to what you are saying but partly for me the suicidal and fearful thoughts were just from considering how incredibly intense the trip was. The emotions and anxiety and just general rawness of nature felt so clear on the trip that it gave me some kind of PTSD and flashbacks that lasted afterwards, to the point where whenever I thought back to the trip I would crave death instead, and these intrusive thoughts were getting more and more frequent to the point of daily. I remember having many thoughts were I was so scared of even the thought of tripping that I would immediately start to obsess over the idea of being dead instead.

I knew that wasn't ok at all so I ended up going back on my old SSRIs which, unsurprisingly, massively turned down the intensity knob on everything and brought me back to reality.

I think I struggled with the aftermath for about 6 months. At first I thought my anxiety was cured by the trip, but about 2 or 3 months after I started losing touch with reality. I am better now (due entirely to SSRIs) but still struggling with the generalized anxiety disorder I have grappled with for my life so far

Consider reading this book to deal with your trauma.[1] It talks about how trauma is stored in the body but also offers a few approaches to healing at the end.

[1]: https://www.goodreads.com/book/show/18693771-the-body-keeps-...

Damn. I think you've got it worse than I ever did.

I politely ask you to do two things, if you haven't already.

First is to have someone, something in your life that keeps you accountable. Self-reporting is unreliable. My most recent example: I was on bupropion last year. I literally felt no different with or without. But it was harming me. My only clue was my activity monitor. (Apple Watch FTW.)

Second, never accept "No" or "idk", tenaciously seek the answers you need. Someone, somewhere has some of the missing puzzle pieces you need. Doctors (et al) are not omniscient and if they've not seen cases like you before, they couldn't possibly have those answers.

Be well. I hope things get easier for you.

Thank you for the support.

I am sure I have overstated the risk, or maybe that is just my anxiety talking. I never had any actual plans to hurt myself, just overwhelming fear and dread to the point I wished it would end by any means.

Thankfully I have my wife to keep me accountable

Wait, you accidentally experienced ego death while meditating as a kid!? That's fascinating

If you're willing to share, I would love to hear more. How did you get so deeply into meditation? What was your practice like? What were you doing that got you to such a "bad trip"

I don't know that it was ego death, precisely. I just inferred that from comparing the impact on me with what others reported experiencing. I've heard it also called 'epiphany'.

I was just reading books and pondering. Sci fi, Sagan, Fritjof Capra, Taoism, Zen, some Buddhism. I didn't know any one who knew anything about this stuff.

I started meditating because I was struggling, had a lot time, nothing to do, and was trying to psyche myself up to start working again. I hadn't been diagnosed yet, so didn't know my failings were health related. I thought I just had a bad attitude, was being lazy.

I got pretty good at reaching a trance state. I was stuck on the notion of "no thought". Best I could do was let thoughts float away. So I started my notions of mental exercises. Visualize a sphere. Think of a color and try to see it with my mindseye. Imagine the center of my ego was my sternum and not my head, imagine the world from that perspective. Float above my own body.

So I was just doing my thing, pretending to have an out of body experience, and I slipped into a different state. The idea was really simple. It was like being able to actually internalize a trillion. Or like Fritjof's epiphany of seeing all the grains of sand on the beach.

I had the full impact of how big the universe is and how small I am, the briefness of my lifespan.

It terrified me. I reflexively pulled back, popped out of trance. And then I laid on the bed for a long while, trying to figure if I was back in my room, if I was dreaming, what's real or not.

I came out of it very different worldview. That whole ecological, holistic awareness, everything is connected, and other woo-woo descriptions. Popping that ego-centric bubble for just a moment.

Again, I'm just using other people's words for what best matches my experience. "If you meet Buddha on the road, kill him." and all that.

I don't know if this is the same thing, but in my early teens, I terrified myself during meditation because I got to a point where I felt I could "think myself out of existence" if I had continued along the (mental) path I was on.

Not sure if that's the same thing as ego death but it was terrifying.

Sounds the same. The Void is terrifying. Whenever my distractions stop working -- Hello Hacker News! -- my mind wanders back and everything seems a lot less real.

If you want to delve more into this topic, I recommend this book: https://www.goodreads.com/book/show/25942786-the-mind-illumi...

How are you dealing with that experience now? Did it completely put you off meditating?

re mediating:

I tried to resume shortly thereafter. FHCRC (always doing experiments) had a doctor working on pain and toxicity. Her angle was mindfulness, mediation, hypnosis. Didn't work on me.

Though I do yoga style relaxation, manage my pains, I've not been able to attain trance state again, much less the next stage.

I think it's because I can't concentrate, focus that way any more. Cuz chemo brain.

The only success I've had is with http://thewayofseeing.com. Focus is like a muscle. I've gotten a bit better. But my best effort is mindfulness.

re coping:

One day at time. Happy to be here. :)

I'm glad to hear that you're coping and that you found a practice that works for you.

Wish you well and I hope you have a fruitful journey :)

Apologies in advance for the wall of text, but this is a topic that has occupied a considerable portion of my attention for nearly 25 years. :)

If any of what I share here is helpful for someone, it will be well worth drifting significantly off topic and perhaps over-sharing my personal experience.

That said, my experience is my own - other people's mileage may vary depending on their background and personal makeup. Trust your intuition (and your doctor / therapist if you have one)!

From your comments below (about being able to notice yourself out of existence), it sounds to me like you experienced both udayabbaya-nana (knowledge of arising and passing away) and bhanga-nana (knowledge of dissolution), as well as the other dukkha-nanas (knowledges of suffering) that follow [1].

It also sounds like you are familiar with the Zen analogs for these Theravada terms - sharing them here mostly for other readers.

These are well-known and understood phenomena, at least in Buddhism. Some modern yogis refer to this territory as the "Dark Night", a term borrowed from St. John of the Cross' work describing the experiences from a mystical Christian perspective[2].

The Atlantic had a good piece on this (touching on some relevant research at Brown) several years back [3].

I went through something similar to what you've described here with meditation, and similar to what many others have described here with psychedelics.

It took years of searching, research and growth for me to process and integrate these experiences and return to both a stable, consistent meditative practice and enjoyable / helpful use of psychedelics, including cannabis (which gave me panic attacks for many, many years).

For anyone who is in similar territory but wishes they could continue exploring: Bhajan / Kirtan [4] (example [5]) and Yoga Asana were both incredibly helpful for me, as was a-melodious chanting of various mantra and stotra.

Coming at the problem as a programmer with some understanding of machine learning - I looked at chanting practices as training data for my own biological neural network. A way to re-wire my relationship with meditation / spiritual practices / ego death.

The transition from my atheistic Buddhist practice to a sort of mystical pluralist practice that integrates many traditions was an interesting one, for sure.

I stopped seeing "god" as an absurd, surely-non-existent (for everyone) personal entity and began recognizing "gods" as undeniably-existing (for me) hybrids of:

* helpful anthropomorphic representations of key truths

* helpful anthropomorphic representations for lawful phenomena

* at the highest level: helpful conceptual placeholders for things that are completely impossible for me to describe

As a former atheist, I slowly became more and more comfortable with this framework. I think this was a combination of having grown up in a religious environment; having mystical experiences, searching for answers and finding documentation (independently arising in many different traditions) that closely mirrored my experiences; and feeling like there was tremendous mind-shaping power in a shared subconscious framework transmitted through trance-inducing chants practiced by millions of people over many centuries.

Like many, I would encounter truths through various mystical experiences and find great relief - only to fall back into unhelpful habitual patterns later. A daily relationship with one's personal Gods (in whatever form they take for you) is a very powerful psychological anchor for remaining tethered to truths discovered through mystical experience.

Lectures by Ram Dass[6], talks by Mooji[7] and dharma talks from many different teachers at Dharma Seed [8] also helped considerably.

I have some conjectures rattling around in my mind about _some_ manifestations of mental illness having _some_ of their roots in the territory of ego death (or close brushes with it). Many of us live in a society where all of our basic needs are met and there is ample time for introspection. Moreover, many of us fill a good deal of our non-introspective free time with music, cinema and television which has been shaped (directly or indirectly) by artists and thinkers under the influence of mind-expanding drugs, leading to further introspection (at least this was the case for me and many of my peers).

That is, I don't think someone necessarily needs to even be a yogi to wander into Dukkha-nana territory. Though, to be sure, the proliferation of superficial "mindfullness" practices will add to the aforementioned dog pile of causes and conditions for initial "spiritual awakenings" (for lack of a better term).

I'd love to share my entire journey and more thoughts on this (including 8 years living and traveling in Asia, trying to find answers). One day!

Lastly: if you find yourself in this territory and things are really bad, there are resources available to you! Check out: https://spiritualcrisisnetwork.uk.

Shenzen Young also has really helpful advice about when it's time to seek help from a medical professional: https://www.youtube.com/watch?v=BQ5B70ac_9M


[1] - http://www.buddhanet.net/knowledg.htm

[2](pdf) - http://www.carmelitemonks.org/Vocation/DarkNight-StJohnofthe...

[3] - https://www.theatlantic.com/health/archive/2014/06/the-dark-...

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

[5] - https://www.youtube.com/watch?v=YBso7TPtvJU

[6] - https://beherenownetwork.com/category/ram-dass/

[7] - https://podcasts.apple.com/us/podcast/satsang-with-mooji/id1...

[8] - https://dharmaseed.org/talks/

Thank you for your thoughtful reply. I'll chew thru those links.

I'd be interested in hearing about the actual experience.

I wonder if some have a genetic predisposition to bad reactions to psychedelics. My best friend had an LSD reaction similar to yours (increasingly intense hallucinations until falling on the ground and starting to seize). His brother had a bad experience with psilocybin and jumped out a window. I believe a second brother also had a bad experience.

Makes me even more concerned when people talk about psychedelics as a low risk self-treatment for various illnesses. I myself have had a bad trip which resulted in years of anxiety and panic attacks (although after having done psychedelics many times before).

Yeah I think that the psychological harm, much like some other drugs, can be underrated. Another example of a drug people see as harmless is cannabis, which can reliably give people (including myself) intense anxiety and panic attacks. It is conjecture on my part but I can't think that it is healthy for your mind to subject yourself to intense feelings of anxiety.

These days I steer clear of all drugs except for my SSRIs and alcohol, the latter being basically the only recreational drug I've taken that seems to not put me at some level of psychological turbulence.

Powerful psychoactive substances shouldn't be taken by people who are not mentally 'balanced', meaning just fine, happy with themselves or similar.

I know its easy to say in hindsight, many of us tried those things when we didn't think about it, and it worked better for some and less for others.

I think the old set & setting has some proper meaning here and can vastly bootstrap the incoming experience. Having a calm, even soothing environment, no negative outside influences like badly tripping / drug rejecting friends who can drag anybody down to mud. If one is really unsure, have some friend 'spotting' for you and drag you back and calm down if bad trip comes. If one is in bad mental place, just don't do it, it ain't alcohol which can be taken almost on any mood.

Personally, I've never had a profound trip unless alone, relaxing on the bed with nice music in the background, but that worked for my specific personality.

> Powerful psychoactive substances shouldn't be taken by people who are not mentally 'balanced', meaning just fine, happy with themselves or similar.

Agreed, but part of the problem is that they're often framed by their proponents as a miracle drug that can cure you of depression, anxiety, and fear of death. So people with those problems will often self medicate with them.

And for some people, it totally works. But it can backfire tremendously, and actually worsen those problems. There's a psychonaut meme that there's "no such thing as a bad trip, just a difficult one", but that's absolutely untrue.

I think psychedelics have incredible therapeutic potential, though, and I'm looking forward to a world where they are legal, well tested and researched, and usable in safe environments with trained and compassionate professionals.

I would say you shouldn't have your first trip unless your mental health is stable, or it is in a therapeutic context.

Once you have some sense of what to expect you can more readily use your judgment as to whether you're in the right headspace. I find it can be quite helpful to mitigate mild/moderate anxiety or depression.

"Powerful psychoactive substances shouldn't be taken by people who are not mentally 'balanced', meaning just fine, happy with themselves or similar."

But therein lies the crux of this kind of reasoning: those kinds of requirements are vague and highly subjective - what does "mentally balanced" entail? who determines that?

It would require a high level of self-awareness and even then, some woundings/mental illnesses may not be apparent until some sort of traumatic event (such as a bad trip). It's incredibly difficult to know ahead of time what kind of reaction someone is going to have to such powerful mind-altering substances and IMO although the advice of "set and setting" is important, it in no way will prevent all possible issues from happening.

It's a paradox, isn't it? What person in their right mind, who's perfectly balanced and stable, would willingly ingest powerful reality-altering substances?

I believe it's more about your psychology at the time but also your past trauma that determines how you react to it. Experience with meditation should help with any weird moments too.

I hear what you are saying, but I'm not just talking about generalized "bad trips" similar to my own - I'm referring to people who's physical bodies have extreme reactions (such as seizures) that seem to be outside the norm (although probably not as rare as most think).

the "jumped out of a window" part seems suspect. It's a common anti-LSD propaganda trope but as far as I know it happened only once provably. It's so strange that your best friend would have been the second case of that.

IMHO psychedelics get a bad rap because they are used by people that haven't done even the bare minimum reading and preparation to have an optimal experience. It's not difficult to do, and once you are in the right place, with the right environment and mindset, it's very easy to use the altered mental state to do productive work on your own psyche.

A hammer is a useful tool as long as you don't hit yourself in the forehead with it.

sounds like you have a bit of a pro psychedelic bias here and are minimizing people's experiences. This isn't just some story I heard, this is a person that I know and who I witnessed struggle to heal from literal broken bones over years.

"as far as I know it happened only once provably" = "I haven't heard of it, so it must not exist or be a lie". Pretty unproductive perspective to have...

I find your kind of flippant "well they just didn't do it right" approach a very common defense of various forms of dogma. Maybe you should consider that mind-altering substances can have consequences for even those who approach them in the most responsible way possible.

Similar experience taking LSD(or whatever was on the blotter) when I was a kid. I've done psychedelics since and enjoyed it, but that was my third experience and it was decades before I tried again.

That is what puts me off trying LSD. It seems that unless you live in the Bay area and are friends with certain organic chemists, your chances of getting good quality, real LSD are slim. However, mushrooms are quite easy to grow.

>It seems that unless you live in the Bay area and are friends with certain organic chemists, your chances of getting good quality, real LSD are slim.

Definitely not true. LSD is one of the purest recreational drugs you can buy. If it's LSD it's 'good' LSD. Occasionally dox or nbome are sold as LSD but even that is relatively rare. Also you can just order it online.

I think nbombs are being mixed with LSD

You gotta test. Don't dismiss the need to test.

"Just order it online" make it sound like it's Amazon. In practice you're going to need BTC, a VPN, and several other safeguards.

Empire is just like Amazon

There was a time "just using Amazon" meant a whole setup that was not ubiquitous. People also are passionate about making darknet seem like a scary place, I've seen many askreddit threads about the "scariest thing you've seen on darknet" with anything to the contrary losing consensus very quickly. Found that odd and contrived.

A lot of regularly repeated things you must do don't even seem based on evidence. Like the bible everyone says to follow suggests all these overcomplicated things, it comes off as written by pretend lawyers.

You don't need a VPN and in most (western) countries getting btc is now trivial.

Not as easy as amazon of course but often easier than depositing money in a poker site for example.

And that's not even mentioning that you can just legally order 1p-lsd on the clearnet the same way you'd order anything (though the UK, Germany and a few others have clamped down on it a bit).

That isn't true here in the UK at least, it is easy and quite cheap to get real LSD. Also it's pretty easy to test too

I guess I haven't been that motivated to really look for it, so maybe I'm wrong about availability here.

[...] you're chances of getting good quality, real LSD are slim

How do you figure?

It is not that popular as a drug and there can't be that many people world-wide capable of producing it.

Nah, it's an extremely popular drug and right now it's probably more available than any time since the sixties.

I don't reccomend LSD to anyone. My last time taking it was devastating. Traumatic hallucinations and delusions during the trip and I had anxiety and uncomfortable tactile sensations that took more than a year to dissipate.

I also suffered from intense tactile sensations throughout the trip that lingered for a few months afterwards. I've always had oversensitivity to touch on THC-heavy cannabis strains but I experienced strong synesthesia on LSD which translated to a few months where feelings of anxiety were directly coupled to my sense of touch in my right index finger and thumb

I've had a very similar experience with my hands. I believe it's a symptom of Depersonalization.

If you used to be on SSRIs and they worked, then LSD doesn't sound like a good match.

I regret not taking psychedelics, but I hallucinated from a large dosage of hashish and had visual disturbances for a couple of days after, so I figured it's better to not mess with other psychedelics.

I also got a bad panic attack from a moderate dosage of stimulants(bad idea mixing them) and I could not drink coffee for 2 years, or I would get a panic attack just from the coffee -- it all went away eventually and I can drink coffee without a panick attack now (though it does seem to cause joint pain so I try to avoid it).

>If you used to be on SSRIs and they worked, then LSD doesn't sound like a good match.

Well honestly I had thought that LSD could be great for anxiety and depression under the right set and setting. Since I was very sure I could have a great setting (which I could) I thought that my chances of a bad trip were very minimal. Unfortunately I think I just didn't pay enough attention to the "set" part

> If you used to be on SSRIs and they worked, then LSD doesn't sound like a good match

Do you have any evidence at all to support this claim?

LSD isn't inherently an anti-depressant. The research around psychedelics involves many sessions of intense therapy with LSD used in some sessions to help facilitate the therapy.

Researchers aren't just dosing people with psychedelics and walking away. The drug itself isn't doing the heavy lifting of addressing the problems.

I have absolutely no evidence, just my reasoning that if you are depressed and SSRIs work, there must be something wrong with those serotonin networks and SSRIs working mean some balance was restored; LSD will just blast the same networks.

I was not under the impression that OP did LSD in a therapeutical setting.

>though it does seem to cause joint pain

Wait, you get this, too? I have searched for answers to this and gotten nothing. I have long suspected that my coffee habits correspond to my joint pain, but I have associated it with many other things in a search for truth. Can you elaborate?

It is just an observation that I made, the research seems to be mixed.

My joint pain started a couple of years ago (early 30s), with really bad pain in my thumb joint after some exertion, X-ray or MRI showed I had some inflammation and excessive liquid, the pain went away after one month or so; then I got pain on the outside of my elbows (perhaps from incorrect posture and lifting my toddler all the time); I originally thought it had to do with my nicotine usage, but I quit for some good months and nothing happened, on the contrary, I started using more coffee and my pain got worse.

I don't think the coffee is 100% responsible, rather that it exacerbates some underlying condition; but so far it is pretty dramatic -- after quitting coffee for a couple of days, my pain is almost gone -- and that happened for too many times to be just a coincidence(though it could).

Mental disturbances from hashish and psychedelics, while similar symptoms, are completely different internally. I wouldn’t rule out psychedelics based on that experience.

It wasn't just "mental" as in anxiety -- those were visual disturbances -- tracers in bright led lights, bright spots in grill patterns (metal or my chess-pattern shirt). The experience just made me think I'm predisposed to HPPD so I thought to play it safe.

Can you share more about the context of the trip? Typically mindset and setting have a big influence. Were you in a safe environment with people you like and trust? Thanks.

Yes, first time was on a canal boat (EDIT: my father-in-law's boat, but he was away) with just my wife. Very safe and secure setting.

Second time was at a very small psytrance festival with my wife and her parents. I trust them completely and they are both very nice, and there were not any scary people about.

Also hoping you move towards recovery and it sounds like you have good people in your life to support that.

I would say that a festival (even small and friendly) is possibly not the ideal place to take psychedelics, unless you're very experienced. If you are particularly prone to paranoia, it can surface with psychedelics (even Cannabis) even in good settings.

I suffer from diagnosed generalised anxiety disorder (GAD). Weirdly that second trip was actually much more relaxed and enjoyable during the trip than the first alone with just my wife on the canal boat, even if I did almost pass out at the start.

Thinking back, your experience of the seizure thing sounds similar to what a friend of mine experienced, not with LSD but MDMA. It is possibly related to the motion sickness and brain poisoning reflex.[0]

[0] https://en.wikipedia.org/wiki/Motion_sickness#Defense_agains...

This is what it made me think of as well. My first experience with MDMA started out in the grips of anxiety, trembling and feeling multiple uncomfortable symptoms, afraid I had taken too much. I don't think I was able to even stand or walk for several long minutes.

I went on to have a wonderful & memorable experience, feeling closeness & positivity with every human interaction for hours. The worst part after I got over the initial freakout was coming back down. I've heard people talk about such early-stage freakouts happening on other psychedelics, too, but I don't have much experience there.

Serotonin is involved in regulating the digestive system so if you take drugs that act on serotonin like LSD or MDMA symptoms like nausea are quite common.

I did experience motion sickness on LSD so could be related

Hope your recovery keeps moving in a positive direction :).

Thank you

I don't want to downplay the negative effect it had on you and the difficulty you're having integrating the experience, but it's possible that long term, confronting those thoughts and feelings directly and coming through the other side will end up being better for you.

Everyone has to confront their own mortality eventually.

>confronting those thoughts and feelings directly and coming through the other side will end up being better for you.

I am not sure whether this is actually true, or whether the rumination and pondering will mess me up more

Well, hopefully you can come to some resolution about what it all means. I went through something similar after a bad trip and it made me focus on what’s important to be doing in life with the time I have left.

Personally, I think that the effective ban on psychedelic research is a crime against science and mental healthcare - given its immense potential. Sure, there are risks, but we routinely use drugs (as in: medications) of far worse side effects! For some reason, reading Grof felt like reading "Solaris" by Lem - on forsaken, unreal research. I am happy to we are slowly starting research into that.

I recommend "Realms of the Human Unconscious: Observations from LSD Research" by Stanislav Grof (https://www.amazon.com/Realms-Human-Unconscious-Observations...) - he was one of the pioneers into psychedelic research, while it was easy and possible. For many aspects, it is... humbling. It seems that visions/senses/experiences of cosmic unity, or unspoken dread, or going beyond the physical world is more of a common theme of LSD.

However, I am torn, when it comes to its lack of skepticism. On one hand side, he hints that some aspects of extrasensory perception (e.g. clear visions of spermatozoid entering an ovum, visions of one's ancestors, etc) can be real, without noting some typical biases (e.g. people reporting coincidences only when they happen). Same, he seems to accept a lot of Freudian stuff uncritically. On the other, I am really happy he didn't censor the stories (or himself!) and share both processed and raw experiences. The overall narration is in the tone of a curious researcher knowing that he may get answers he is not looking for.

Overall, I recommend it a lot, keeping in mind that you don't take too religiously his mentions of Freud, Jung, birth matrices and extrasensory perception too literally. But... as a lens/perspective, that (though flawed/simplified) can yet be fertile.

> Personally, I think that the effective ban on psychedelic research is a crime against science and mental healthcare - given its immense potential...I am happy to we are slowly starting research into that.

Have you thought about supporting the people who have been laying the groundwork for the current wave of research (e.g. https://www.heffter.org/)? This new crop of research owes a lot to this group's decades long mission to bring psychedelic research back to acceptability.

[no affiliation other than knowing some of the founding board members]

also MAPS,

> On the other, I am really happy he didn't censor the stories (or himself!) and share both processed and raw experiences

This should be the default reaction when it comes to metaphysical phenomena like ESP, consciousness, and the like. If he had self-censored, that's less of another human's experience shared.

Sure, enough off-beat ideas label you as a kook, but I think if we entitled every human to one or two write-off beliefs, without labelling them as a kook, we'd discover more interesting things about the world. It's so easy to go, "that person believes in X, clearly they lack skepticism" and write off every other stance by them. Instead if we the listener accept these data points as "interesting but potentially erroneous" we can build better mental models than if we reject outright ideas contrary to our worldview.

> However, I am torn, when it comes to its lack of skepticism.

That's a common theme among psychedelic researchers.

Slate Star Codex wrote an article about it: https://slatestarcodex.com/2016/04/28/why-were-early-psyched...

Every time I read a book or listen to a podcast from a prominent psychedelic researcher, I'm caught off guard by at least one or two bizarre, anti-scientific statements.

With Stanislav Grof, it's his insistence that "synchronicity" is the mind directly manifesting experiences in the physical world. This is an actual quote from Grof:

> What's characteristic for synchronicity is that it seems that the psyche is entering into a kind of a playful interaction with the material world, where something happens in your dream or in your visions, and then the material world kind of plays it out. Let's say you have a powerful shamanic experience involving an owl, and you walk out after the session and there is an owl or a wounded owl and so on.

I suspect that psychedelics might be useful adjuncts for professionally-guided therapy because they open the mind to suggestibility. I suspect that same suggestibility might be dangerous when repeated frequently without external direction, as is the case with many prominent psychedelic proponents. These people begin to believe their own hallucinated thoughts and realities.

It's important to note that the vast majority of psychedelic research doesn't involve dosing people with psychedelics and walking away. Instead, the research revolves around intense therapy sessions where specific sessions also involve psychedelics. Internet articles tend to disregard the therapy portion and write headlines that lead people to believe that psychedelics are inherently anti-depressant, which is a dangerous mischaracterization of the current research.

> Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution.

This is interesting. Is there any practical techniques on how to induce the latter form of ego dissolution?

Eat mushrooms, apparently.

For me, psilocybin removed data filters and allowed my mind to receive data without mental heuristics prejudging my senses. I saw light and not objects, I saw more color where I knew there should be less, and I viewed bugs and plants as other beings occupying the same space as me.

"Set and Setting" https://en.wikipedia.org/wiki/Set_and_setting

"Of course, the drug dose does not produce the transcendent experience. It merely acts as a chemical key..." — Timothy Leary (who ought to know.)

So narcissism and egomania could possibly be a result of a bad diet?

Would IF help?

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