Importantly, this tracks with what we know about the protective effects of things like religiosity against depression. As such, the qualitative experience of the drug might not be something we can (or should) do away with. I would even go as far as suggesting that an absence of transcendence in one's life is precisely what causes a large segment of people to become depressed in the first place, and that perhaps drugs are helpful only insofar as they produce a transcendent experience.

This isn't to say we can't take a scientific approach to treating depression, but that has to be balanced with something profoundly metaphysical: the actual qualia of life experience. Wellness isn't the absence of disease; it's the presence of thriving, and that includes within it a component of things like hope, inspiration, and elevation above the ordinary. We used to have various ceremonies designed to turn us towards the numinous, but we've pretty systematically dismantled those in favor of a grounded hyper-rationality [1]. As a scientist, I can't really object to rationality on its own, but it may be worth considering non-rational, transcendent experience as a fundamental psychological need.

[0] If you're a materialist, you might object that neurological machinery is not differentiable from qualia. Fair enough! I even agree! My point is simply that medicine needs to consider qualia as a major parameter in the treatment of depression. Fixing depression is not like fixing a car.

[1] I suspect most people here are familiar with Nietzsche's "God is dead quote". Many people in my entourage are floored to discover that he correctly predicted the dramatic increase in anxiety, depression, neuroticism and nihilism that is present in modern life.

Ketamine dosed at levels used in a lot of the original depression studies won’t result in anything resembling a “trip”. Many of the more responsible clinics will carefully administer IV ketamine infusions over 40 minute (IIRC) spans at levels that only result in a little dizziness.

The association between ketamine depression therapy and “tripping” is a more recent development, pushed partially by clinics and influencers seizing on the trend in the most dramatic way possible. Some of the clinics will now dose people with excessively high doses with the goal of inducing trips and overt experiences, even though this isn’t supported by the literature.

I’m actually growing concerned that the pop-culture obsession with tripping and the over zealousness of ketamine providers is going to result in regulatory crackdown on the whole process.

A few months ago I was discussing the topic with a psychiatrist friend. She had tried prescribing ketamine for several patients, optimistically. However, a number of them complained that it wasn’t enough because they weren’t having full on hallucinations like they had read about online or in books. Several of them also started trying to demand higher and very early refills, despite her explaining up front that she was only willing to follow the dosing protocols used in studies.

I would like to chime in a thought about the choice of words... I think that we might be doing us a disservice when reducing the whole discussion down to "trip" or "no trip". Some patients have mild sensory experiences from the treatment, some have unpleasant dissociative-ish experiences, some done feel much at all. My belief is that the subjective experience, or the phenomenology of the treatment, is of importance even if the experience is far from a "trip". My patient who thus far has had the most convincing response did not "trip", but described a calm feeling of "everything will be alright" during the treatment - a response that none of 20-ish drugs or ECT had given.

I do not have experiences with psychedelics, but I do have quite some mileage with meditation, in particular approaches that aim at shifting the "way of looking". Those practices can lead to experiences that lead to profound shifts in the usual day-to-day way of looking at the world, but the experiences themselves are more subtle than what I expect a full blown trip to feel like. So I can totally picture that the experience, even if just subtle, can be a big part of the transformation.

I'm not sure if I remember correctly but I think I've read ketamine makes neurons groe new dendrites in petri dish. I have no idea how this effect could happen in the brain without making a patient trip.

I interpret you as saying that unless there is a "trip" there is only a placebo effect left on the table so to speak. I think this is somewhat refuted by the fact that the standard ketamine infusion protocol (that does not normaly induce "trips") has an effect size that dwarfs the effect size of placebo (say 0.2 - 0.4). Some studies have shown ketamine approaching ECT-effect sizes. This makes me sound like a ketamine nut, which I am not. I am a bit of an ECT nut though. I have just not excluded the fact that the phenomenology of certain treatments actually mediate the treatment effects in a non-placebo way.

At least it is what authors of this study consider.

Also consider the difference between high and low doses of alcohol: just because having 1 beer won't make you blind drunk doesn't mean that the effect is a placebo.

I only say all of this to ask: Is there a scientific or medical definition for a trip? Is the medical community still trying to decide what constitutes a trip, or is that well defined?

In this way, your psychiatrist friend is simply the next iteration of a priest, and the portrayal of her patients as greedy fools only furthers this divide and pushes ever more people towards the other side of the law. I'll see you in _my_ cow field with a woven basket!

_edit_: think of it this way. An internal urge drives people to your friend in search of a meaningful experience. Your friend consults her good book and returns to them with information: no, you cannot have your meaningful experience.

This really isn’t about being a lawful authority trying to buzz-kill society as much as it is about having principles as a doctor. The patient wants a cure to an ailment while their doctor has no evidence of its efficacy.

If I had someone coming into my auto repair shop telling me they didn’t need brakes, they let Jesus take the wheel like they heard in the song, my noncompliance to their request to remove them from their vehicle does not make me a gatekeeper like the Catholic priests you described.

What I broadly mean is that modern society has done a relatively poor job at helping to produce integrated humans that have the capacity, tools, and know-how to navigate their inner journey. I know this sounds woo to a lot of people here. That the new wave of psychedelic interest is reified as purely medical treatment is a continuation of this trend. That is what I'm trying to articulate.

I have a deep suspicion that you can't simply sterilise the transformation at the heart of these experiences.

And anyways, your statements ignore that there's plenty of hippies on Instagram peddling their mushrooms and Ayahuasca in intense spiritual experiences for only 1500$ a pop. Does the Catholic church control them too?

Dostoevsky made observations like this, too.

"It was not you who ate the idea, but the idea that ate you"

"Men need to bow down to something; whether another man or an idea.”

I think Ernest Becker explored similar ideas in The Denial of Death, though through a different context.

Somehow you turned someone's subjective spiritual exploration into them limiting themselves...

When people tell me about their psychedelic trips, I am like, so? I’ve been doing it my whole life without drugs!

However, my tendency to go on these trips are highly affected by environmental variables. So the only thing I would add is, it’s a mix between the spiritual and the material And we cannot negate either.

So all these therapist and psychiatrist trying to cure me are taking the wrong tact. What I learned is I needed to understand it, and understanding it alone is the cure.

Its such a dellusion that humanity has been "pure" at any point in time. Drug prohition, and all its tenticles, is a political tool of mass control. Nothing more, nothing less. Today we are seeing the reemergance of the teachings that have been passed down for generations by tribes around the world as this viel is lifted.

So please, this is not a trend. Its a rediscovery of aincent knowledge. I appreciate that low dose is how this remergence started, but there its not a cureall, and its not the only way this sustance provides benifits. 20 years ago, these same people were trapped to tables, eletroshocked until they became cataonic. Heroic doeses have their place in therapy.

This is hugely beneficial, until it isn't. Having the ability to utilize multiple lenses to see things in a different perspective allows us to unrecognize the threats from our most used perspective.

The over recognition of threats, particularly those you can't control, plays a major role in depression (rage) and anxiety.

Everyone has a default perspective but getting deeply involved in anything can allow us to gain additional perspectives.

Religion provides an alternate perspective. E.g it is the will of Allah, Jesus died to save me, ending any suffering ends all suffering, etc.

With that when you look at things you can apply those perspective filters and see things differently.

Deep interests are filters as well. An example that is a personal anecdote is when I became involved in woodworking and construction I look at houses and "see" how they were built, I see the components, the connections etc, I see trees as board feet and just intrinsically visualize their milling.

It happens with other things as well and it can bring anxieties too, I'm far more concerned that some buildings are going to collapse at random after I have been involved in construction.

Religion can of course add anxieties.

Any new perspective can. Having a new perspective / different way of thinking, on a physical level is a rewiring of connections in the brain. The perspective can become reflexive, mental muscle memory.

The activity of drugs is to induce this rewiring effect. Changing the actual way the brain works by binding to receptors and forcing new connections or reroutes.

Historically people would play many roles, typically changing with the seasons, each which offered a different focal perspective.

As well they would have a deep guided religious experience, use perspective changing drugs and have a strong notion of either self or community which offered further perspectives.

Today many people follow the same path and pattern far too frequently. Affording very limited development of alternative perspective. This leads to a much more developed recognition of negatives due to lack of diversified perspectives.

What else could happen though, it's often, daycare for 3 years, school for 12/16+ then work for 30-40 years. Perhaps there's a year or even just a couple summers of exploratory travel, then we're relegated to a few weeks of vacation and commercialized cultural holidays.

Pop culture "obsession" may have been useful for overcoming blanket bans on research, funding, etc. It was obsession that created these bans in the first place, and obsession that triggered them.

Now obsession it's interfering with science and (especially) science communication.

Meanwhile, parent comment (the "trip" is the active substance) is a hypothesis... on the face of it. A reasonable hypothesis that needs to be considered, and if possible tested.

There's probably no getting around obsession here. This is literally the namesake "culture war," dating to 60s counterculture.

Anecdotal first hand account, I would have to completely disagree with you. I tried intravenous ketamine therapy about a year ago. I’m plenty experienced with psychoactives, having experienced several at varying doses, so I knew what I was in for. My IVKT experience was a full on trip, definitely not just passive dizziness.

The "standard" pathways for most substances is to build a tolerance to it (and similar compounds) over time of use. If you drink coffee a lot you don't get hyped by the same dose of caffeine, if you drink lots of alcohol it's harder to get you drunk, etc.

So if anything I'd expect "veterans" to be less sensitive to it. But there are substances that permanently reduce your tolerance to them, usually by causing some form of permanent damage, so it's possible that you might "break" something limiting your experience.

Depends on the dose. If you poison yourself with caffeine later you can get very sensitive to even small amounts of it.

It certainly FELT to be a property of the transcendent experience and not a biological side effect of the substance.

Being blasted out into the infinite space of all possible chaotic realities but being able to successfully "crawl back" to THIS reality as an oasis / point of stability was a life changing experience. Although it was what you'd otherwise describe as a "bad trip", it flipped a switch in my brain from "existence is pointless" to "existence is a miracle."

Haven't felt existential dread since.

And you don’t need to mountaineer

And also trips. From my own experience I’d say they changed me profoundly. But I’d rather be cold, hungry and tired now thanks:)

Psylocybin was by far the most intense experience in my life (and I've been to both births of my kids and cut both umbilical cords, that was intense), all of those few times I tried it, some 15 years ago. Had a standard dose in dried form that I grew myself from growkit from Amsterdam, but mixed with raw lemon juice, which based on some erowid reports dramatically increase intensity while making trip shorter. I'd say its actually a cheat - you get some of the effects of efforts that others take years or decades to achieve, ie via meditation. But effects can be random (ie based on your personality and unresolved issues), both good and bad. And you get absolutely 0 of 'character building' which happens only if you face actual obstacles in life and overcome them with your inner strength, or via sustained focused effort on some goal.

I can attest that instead of rather mild 6 hour experience (1 dose on non-empty stomach of almost 100kg male isn't that much), with lemon I've had maybe 2.5h absolutely brutal trip of dissolution of myself, ego, senses and everything else into mist of atoms, swirling in background music like hot steam droplets in wet sauna. I was laying in the bed, alone, with nice shamanic music in the background, eyes closed. Coming down back to reality one nanometer at a time, rediscovering my senses, body etc was very very interesting and pure happiness-inducing. Then afterwards an absolutely brutal headache, literally feeling I've burned every last energy molecule with that expanded mind, and now whole brain is spasming. Still worth it.

Whether it rewired something in my brain or changed something I cannot say, I didn't have any previous issues (and TBH if you have ones, stay the fuck away from these powerful substances, the chances that they will mess you up for long/forever are non-trivial. Rather work with the issues sober and come to this afterwards, or in future hopefully this can be done with professional supervision).

Mountaineering or generally coming close to death and overcoming the fear of it on the other hand is something you do sober, you can do every weekend without your friendly neighborhood drug dealer, and it just improves your health and happiness (not so much during the adventure if its intense, but definitely afterwards). I'd say proper climbing is distilled essence of mountaineering - just focus on scary parts, where you battle with your mind which just wants to give up dangerous stuff and go home. You can't reach the top if you can't conquer your fears. Now do it a hundred times during 1 evening, once of even few times a week. I've come close to death a few times, but those experiences don't have immediate massive effect, rather they are being incorporated one 'atom' at a time into your personality.

I'd say both leave lasting effects, but how do you want to measure subtle gradual changes in one's personality. Haven't touched mushrooms for 15 years, never had a bad trip but I feel they gave me what they could, and continuing is just about getting wonderfully wasted. For father of 2 amazing small kids this is absolutely useless, a bit of weed here and there is enough for me to process anything these days.

So, naturally when westerns come and want to isolate compounds and get rid of the ceremonial background because it’s “unscientific”, the only possible reaction is to put one’s hand in the face and think “here we go again, THIS too will be colonized.”

This world has far many more dimensions than what modern science is able to address. And many of these plants/compounds open access to these dimensions. It’s really important I think that we have the humility to learn from the people who have worked with these medicines for a very long time.

Context: I have apprenticed and studied very closely under various traditional lineages for the past few years.

Otherwise, I write about the relationship between technology and spirituality here: https://louison.substack.com/

You may also get more information about traditional indigenous ceremonies/sorcery reading Carlos Castaneda, Ruiz or looking for other books in that category.

My experiences seemed to benefit more from watching David Attenborough and feeling a connection to life.

I’d interpret the dad of a family of mountain lions as an analogue of my dad, etc. Seeing events as taking place in a dissociated context. All that introspection is what I found useful about Ketamine.

Yeah, sounds silly. But it made me a happier person. To my understanding and experience, these function more to temporarily remove neurological filters than really add much new (same with LSD, etc). Maybe that benefit is “subjective,” but what’s the difference to me, years later?

It only sounds silly to our modern sensibilities, which I am increasingly considering regressive on the specific question of "what is a life well-lived".

To a pre-modern society that considers e.g. dreams to be vehicles of important meaning, religiousity to be a good thing in measure, idle time to be a gift and introspection to be one of the major points of existence, it doesn't sound silly at all. It sounds wise.

I'm a scientist by training and an engineer by trade, but as an empiricist, I am forced to admit that my life has gotten better by making room for the irrational, superstitious, obliquely-associative, self-contradictory omginternets to exist. Make of that what you will ;)

Social media selection bias at play. The real world results are very mixed, but usually don’t result in life changing benefits that you read about in selected stories.

There’s also an unhelpful bias toward purely positive stories on the internet. I had a friend get addicted (yes, addicted) to psychedelics who could not stop acquiring and dosing them on a weekly basis for years. It was a huge problem, but strangely when I mention this story people will rush to argue it, deny it, insist I’m lying, or try to downplay it with the old “psychological addiction isn’t physical addiction” gimmick.

Like exercise can make you feel fantastic, these experiences ground you in the reality of existence.

So the suicide watch monitoring somehow didn't happen. Not unique to ket or psilo. Not at all.

A corollary of my position is that you should be able to fix a fair bit of depression by providing non-pharmacological access to transcendent experience. The drug is then a (very potent and correspondingly sharp) tool among others.

Everywhere there is huge gatekeeping from these experiences, or from life in general. I definitely agree with people who say that our society is spiritually bankrupt. It isn't that they are missing some essential doctrine or belief or they will be damned, it is that they can't give themselves up to life fully if they have no recognition of the Absolute.

> Reverently contemplating Amida’s directing of virtue for our going forth, I find there is great shinjin [faith]. Great shinjin is the superlative means for attaining longevity and deathlessness. It is the wondrous way to awaken aspiration for the pure and rejection of the defiled. It is the straightforward mind directed to us through the selected Vow. It is shinjin* that actualizes Amida’s profound and vast benefiting of others. It is true mind that is diamondlike and indestructible. It is pure shinjin by which a person easily reaches the Pure Land where no one goes. It is the mind that is single, realized by the person who is grasped and protected by the compassionate light. It is great shinjin, rare and unsurpassed. It is the quick path difficult for people to accept. It is the true cause of attaining great nirvana. It is the white path by which all virtues are fulfilled instantly. It is the ocean of shinjin that is itself suchness or true reality.

Shinran Shonin

> Shin Buddhist practice is not based on belief in an uncertain better future but instead places emphasis on the present moment—a moment made possible by the causes and conditions of the past. Many take for granted the efforts that generations of humans have made, along with the interdependence of all life forms, that contribute to our being here now.

> Reciting Amida’s name is like an alarm clock that says “Wake up!” to the joy of being alive each and every day. Awakening to this rare gift of life, we can accept and endure the wide spectrum of human grief and bliss and become a source of happiness for others.

Buddhist Churches of America

That's very unfortunate, seeing as it's the entire point of religion...

Your experience tracks very closely with my involvement with Roman Catholicism in my childhood and adolescence. It's frustrating beyond words, and has largely put me off from participating in religious institutions.

Thankfully, there are some incredible thinkers who have written books!

I remember the first time I ever tried a benzodiazepine. I then realized I am anxious most times, that that default state is not ""normal" and that you can actually change it. And for brief periods of times I was able to re-create the effects of it at will. Also just having a xanax pill in my wallet cured my panic attacks.

My hypothesis is that even "temporary" positive psychological experiences can have profound effects on the brain, show it there is a better state and in certain conditions the brain will figure a path.

I don't know when I learnt to move my ears, twist my tongue sideways or when I self learnt "voluntary tubal opening", but without going into mumbo-jumbo, I think there's a lot more we can control about our brains and bodies than we think.

Which brings us to the second most famous statement in all of modern philosophy: Nietzsche's "God is dead." The year was 1882. (The book was Die Frohliche Wissenschaft [ The Gay Science ].) Nietzsche said this was not a declaration of atheism, although he was in fact an atheist, but simply the news of an event. He called the death of God a "tremendous event," the greatest event of modern history. The news was that educated people no longer believed in God, as a result of the rise of rationalism and scientific thought, including Darwinism, over the preceding 250 years. But before you atheists run up your flags of triumph, he said, think of the implications. "The story I have to tell," wrote Nietzsche, "is the history of the next two centuries." He predicted (in Ecce Homo ) that the twentieth century would be a century of "wars such as have never happened on earth," wars catastrophic beyond all imagining. And why? Because human beings would no longer have a god to turn to, to absolve them of their guilt; but they would still be racked by guilt, since guilt is an impulse instilled in children when they are very young, before the age of reason. As a result, people would loathe not only one another but themselves. The blind and reassuring faith they formerly poured into their belief in God, said Nietzsche, they would now pour into a belief in barbaric nationalistic brotherhoods: "If the doctrines...of the lack of any cardinal distinction between man and animal, doctrines I consider true but deadly"--he says in an allusion to Darwinism in Untimely Meditations --"are hurled into the people for another generation...then nobody should be surprised when...brotherhoods with the aim of the robbery and exploitation of the non-brothers...will appear in the arena of the future...

Nietzsche said that mankind would limp on through the twentieth century "on the mere pittance" of the old decaying God-based moral codes. But then, in the twenty-first, would come a period more dreadful than the great wars, a time of "the total eclipse of all values" (in The Will to Power ). This would also be a frantic period of "revaluation," in which people would try to find new systems of values to replace the osteoporotic skeletons of the old. But you will fail, he warned, because you cannot believe in moral codes without simultaneously believing in a god who points at you with his fearsome forefinger and says "Thou shalt" or "Thou shalt not."

This is confirmed by the linked study (which shows that placebo-ketamine is also very effective).

This view ignores the major application of these substances. Ketamine-induced self-therapy is accessible instantly and acts as a major reset. When you are experiencing long-term depression and/or anxiety, the advice to "just meditate" or do deep introspection is wildly counter-productive. Depressive state is very frequently accompanied by an unhealthy focus on the internal voice and on over-analyzing own life/motivations/purpose/etc. Having an "introspection session" in this state is a borderline dangerous advice.

There are corresponding risks to this, of course, but that's the flip side of their utility as a (sharp) tool.

Yes I might actually enjoy having countless shards of the universe's ideas slicing through my ego for a few hours at night over the weekend; no I never want that to experience that during a workday.

Not just overrated, but most likely the core of the problem. It displaces so much and returns so little.

I'm not sure what your point is, beyond perhaps "don't do drugs all the time?" If that's it, I don't think anyone here would object.

Here's one showing a mechanism ketamine and antidepressants both act on:

https://www.science.org/content/blog-post/how-antidepressant...

Depression seems to have more than once cause.

I couldn't agree more, you've made really great points that allowed me to reflect on my own approach to my mental wellbeing. I honestly needed to see this comment right now. Thank you!

If you want me to really tickle your noodle, consider that a lot of modern-day issues stem from a quest for transcendence in a society that has largely dismantled the institutions capable of delivering it. In particular, I am of the (somewhat provocative) opinion that things like radical Islamic terrorism, fringe climate activism, and the more virulent brands of third-wave feminism are all, at their core, performative quests for such transcendence.

But that's all secondary to the fact that I am glad my comment is helpful to you on a personal level :)

Interesting thought. If you have a blog, I'd like to read more.

That sounds like a middlebrow dismissal of what these groups are. I think you can describe them with more tangible psychological/philosophical motivations which I don't find useful to describe as "transcendence" e.g.

- belonging : the appeal of the gang, the cult is to find acceptance, your tribe, your family. If life has thrown you to the curb and vulnerable, such organisations will take you in.

- guru syndrome : the search for a paternal figure to structure and make sense of the world, to surrender to, to love, to give devotion, to follow, no matter the path

- meaning : a thirst, an existential emptiness, a desperation for life to have a purpose, any purpose

- rationality : extreme groups are often fighting a real injustice and the tactics often have reasoned philosophical basis - we may not like them, may consider them immoral, but they are often more deeply thoughtful than who they fight

- emotion : the injustices are often personally experienced by their adherents, they are angry, they may seek not just redress but revenge, it's a cause which attracts them as a moth to a flame

- stimulation : the dreary day to day, the monotony vs. the thrill of action, the fight or in some cases straight-up sociopathic indulgence

People are giving themselves to higher-order causes beyond material comfort. They are organizing around rituals of belonging, gurus, directly seeking meaning, applying rational thinking towards advancing their values, experiencing deep personal emotion around systemic or cosmic injustices, and deriving a sense of elevation among "the dreary day to day".

The post is irresponsible. No one should be thinking that some sort of "transcendence" will solve their issue, or that is what their problem is.

Always discuss treatment with a psychiatrist.

If you're depressed because you have a chemical imbalance then you're a great candidate for SSRIs and the like. Serotonin? In this economy?

If you're depressed because your life is miserable in some fashion then there's a lot of potential options but this sounds like what you're talking about with K as one treatment.

If you're depressed, you don't respond to SSRIs and "my life is good, why am I still like this?" describes you I think the parent is saying that transcendence is potentially one treatment for this.

How does one evaluate if a new drug works vs depression when there isn’t a consistent diagnosis or presentation of the symptoms.

An alternative explanation for this is that if you keep giving people different drugs and different diagnoses eventually they will feel better for unrelated reasons and will assume the current diagnosis/drug combo is what “fixed” them.

The main interesting thing about ketamine was that there were some anecdotes that the effects were very rapid - and that should be at least something to make it easier to assess a change. But maybe harder to separate placebo.

I agree it is interesting that ketamine seems to work very quickly for some people. Re: your placebo comment, I also agree it's hard to separate it out.

One of the tricky things with the placebo effect is that there are really multiple distinct types of placebo effect; on the one hand, you have objective measurable biological changes that placebos can trigger, but on the other hand placebos can also affect peoples' subjective perceptions of the symptoms they're experiencing.

In the case of depression though, the subjective perception of misery is the core problem we're trying to fix. Hence why treatments that have no biological effect (like, e.g., therapy) are still considered valid approaches. So, then the question is, does it matter whether ketamine is just a placebo? Maybe all antidepressants are placebos, in which case the important thing is to find the safest, most effective, fastest-acting placebo we can.

Really though I do kind of think peoples' subjective experiences matters in a more concrete way than folks give credit for. Even though it's not directly modifying your brain chemistry, I wouldn't call therapy a placebo, for example. Maybe sometimes medications help people because beliefs like "someone is trying to help me" or "I've found an explanation for why I feel bad and there's a treatment for it" actually help people break out of their self-destructive patterns, regardless of the actual efficacy of the meds. It's more questionable though whether those beliefs actually help with long-term root-cause fixes though, or if they just trap people in a local maxima.

See also: "you're not anxious; you're distracted."

I once attended a talk by a neuroscientist at UCSF, Adam Gazzaley, that really helped me see what the future of medicine could look like if we appreciated the power of experience, and more importantly if we could measure and then alter said experience in a realtime closed-loop system. My takeaway was that one day we might think of blasting our synapses with SSRIs or Adderall similarly to civil war era surgeons...the bone saw does prevent gangrene, but in a such an inefficient way.

As a materialist I think it's absurd. But I think that trip is sure sign that the substance actually does something to neurons. And in case of some substances like drugs if you reduce dosage or adjust protocol so that trip doesn't happen means that you also got rid of any significant effect it might have on the brain.

In my opinion saying that experience of the trip healed me is a bit like saying that my experiencing of reduced immobility of walking in a cast made by bones fuse together and heal, mind is so powerful.

But there are a lot of different ways to do the healing (e.g. consistent meditation as others mentioned) which will of course be coupled to different feelings/experiences. The "large psychedelic dose" method is just one end of the "works fast + feels strongly" spectrum. Of course as the science/technology develops we will find other points on the spectrum that balance the properties differently -- maybe even through placebo effect alone as suggested here.

We agree. My point is that the evidence seems to be going in the direction of:

1. removing transcendence removes part of the benefit; and,

2. to complicate matters, many protocols fail to properly control for transcendent experience because a lot of control groups are placed in a quiet room, free of distraction, and invited to ponder life.

We're both materialists. Mine is a materialist position.

I'm not quite sure about you because you are using words like transcendence. ;-) In my view the deep experience of the trip, what you call transcendence, is just another hallucination, just hallucination of meaning and understanding instead of simple images, sounds or sensations.

If they are different (and exist at all) then such needs to be demonstrated before they can be reliably considered.

Given even proponents of qualia can’t reliably agree with each on what they even are defined as (other than using vague circular reasoning)… frankly, I’m not holding my breath.

No, they are definitely not. I don't see anything in these studies to the effect of "hey, it's the feeling that they feel that's making them better". They're looking for some mysterious mechanism, usually on the cellular or molecular level, whereas "numen" and "transcendence" are not even on the biological level of analysis.

That’s called “the placebo effect” and it’s one of the most studied & controlled for factors in ANY medical testing.

I’m fine with including other phenomena. As I said in my original comment though: those phenomena need to be demonstrated to exist, first.

Until then it’s absolutely unscientific, and medically unsound, to assume they exist & then hope that they magically work. Because that is not science: that’s quackery.

If I'm being pedantic here, it's that I really don't want to downplay the importance of the pharmacological level of analysis. It's a very useful analysis. It's just not a complete theory of life well-lived.

Believe me, I’d be the first to suggest they be considered if we had that. We don’t. It would be great if we did.

Until then it’s not medicine, it’s shamanism.

The “substantial revisions” after 17 years to that paper are—rather weak—responses to objections raised in the 90s and should have been in their 2002 paper. Worse, they’re responses that have their own major objections by 2002 anyhow.

Not sure what your aim was but I guess thank you for underscoring my point rather perfectly?

I suppose that the reason people might object to such idea is that they are implicitly committed to a form of positivism and they sense that if people can experience evaluations then the fact/value distinction is undermined. Therefore I think that while it is understandable what you mean when you use the term "rationality" as equated with positivism it would be good for the long term debate to separate those two, since I take it that people like us would like to have it both: science and a form of atheistic mysticism [0].

Ultimately the grand-father of rationality, Plato, was anything but a positivist.

[0] I use the term mysticism mostly because I lack any better term. Evaluative intuitionism is probably the most correct technical term but it has historical roots which I dislike because it was constructed around the single intuition of what is Good, and I believe that we need a wider range of evaluative terms to adequately describe our experiences.

Bleak utilitarianism is why so many reject applying themselves to a deeper understanding of the world, willfully ignorant in a way to manufacture wonder via a lack of comprehension.

It starts early, with the sexist trope of Eve plucking an Apple from the tree of knowledge and getting us kicked out of the garden eden. Bullshit.

I agree with the OP, the trip is the point. Travel, see the universe.

Based on observations of the Rationalist community over the years, I would say that it is possible as a rationalist, but not as a Rationalist, in that they tend to believe our knowledge of reality is limited to that which is endorsed by science.

I always took the mechanism to be community, that sort of thing. I guess if you're right we'd expect Pentacostals to be protected more than Lutherans, etc.? Do we have any idea what data is out there that might be able to disentangle this sort of question?

I notice that many transformational psychedelics stories involve some form of previous traumatic experience.

> Importantly, this tracks with what we know about the protective effects of things like religiosity against depression. As such, the qualitative experience of the drug might not be something we can (or should) do away with. I would even go as far as suggesting that an absence of transcendence in one's life is precisely what causes a large segment of people to become depressed in the first place, and that perhaps drugs are helpful only insofar as they produce a transcendent experience.

Fantastic point and so well written. As someone who experimented in my late teens/early 20s, I wholeheartedly agree with this. The experience changed me in a positive way and has helped make me who I am today.

I thought the same thing when reading the article, but then I started to wonder how the fuck would you double blind that?

[0] Mostly. Part of it falls under Dennett's notion of an intentional stance, but that requires us to take self-report seriously, and so precludes a number of experimental designs.

People are able to acquire knowledge in ways besides randomized, controlled, double-blind trials. Nearly all knowledge is acquired in some other way. I say this as someone who writes A/B testing software for a living.

It's bizarre that people would think any different of it?

It's like therapy on steroids.

It's an equivalent of scientist saying that eating an invoice for therapy doesn't get you "cured". Doh?

Religion is community at its heart.. but maybe we need an abstract idea of god to foster that community.

Perhaps being able to keep a perspective on hope and of hope for long enough is part of the shift, assisted by ingestion or not.

Placebo as science is learning is relative. The body does literally change based on thought.

A recent Huberman podcast literally stated the brain itself is a pharmacy and creates certain substances as triggered. Not implying it’s the same for everyone, but interesting nonetheless.

If ketamine/shrooms push and hold a different perspective for long enough that it is difficult to unsee, unfeel or unexperience, that’s kind of interesting for sure .

I've seen the results ketamine can give first hand, and the dangers of it, but I'm more convinced it may just be getting proper sleep given the connection between sleep apnea and depression.

I would bet that if they engineer a version that does not cause psychosis it will work just as well for the population it does work on. And we should not be quick to dismiss psychosis, it's a major risk factor for violence, something I have also seen first hand.

But it is true that ketamine can cure depression, at least for a time. It's effectiveness is not something you merely guess at like most meds, if it's working, it seems to simply get rid of the depression outright.

So... definite potential and definite danger, though I think the trips are likely harmful, rather than being the benefit of it.

I think we all do. Certainly, I struggle with that as well. I think this is an inherent property of undecidable questions (contrary to most well-formed scientific theories, which are valuable precisely because they can distinguish themselves from hopeful thinking).

Here's something to consider: some kind of hopeful thinking may be a fundamental psychological need. When I saw the title of this HN post, I had thought that perhaps this was the question that ketamine researchers were considering, but alas not.

It feels like a slightly abstract application of “it’s the journey not the destination.”

>Tout le monde veut être libre

>Personne veut être seul

>Pas d'ordre à donner ou à recevoir

>Personne à faire rêver ou à décevoir

>Ne rien n'attendre des autres, pas d'espoir...

Or, I could have just as well answered "both, but medicine is ignoring one".

- conceptual layer failure => asylum

- neurobio layer failure => life support

it's like fixing the way you drive your car

This speaks to me for sure...

Ever since I was little, I've had trouble identifying with humanity. Even though I was born into this body, I never really identified with it, never really felt like that was "me".

I wanted fantasy instead, I wanted to be a creature instead, something with fur and paws and a tail. It's gone far enough that I have DID and multiple such creatures live in my head with me.

But I can't have it. I don't hallucinate. I don't even dream of creatures, not even daydreams. I only dream of humans. I only dream of reality. My dreams aren't an escape from anything, they are just more of the same. My imagination isn't an escape from anything, because it's not real. It doesn't look real, it doesn't feel real. It's just a tease.

And this hurts. There is some sort of deep, existential pain that I feel whenever I am reminded of this. "Species dysphoria". If anyone had trouble understanding gender dysphoria before, boy do I have a concept for you.

I don't know what is wrong with me. I don't know what caused me to dissociate from the body. It's supposed to be my body, it's supposed to be one with me, it's supposed to be me. I'm supposed to be comfortable in it, and it's supposed to be under my control. But it's not. It's not me, it's not comfortable, and it's not under my control.

I blame some of it on autism and ADHD. Being autistic deprives me of control over the body, and ADHD deprives me of the ability to override that. But I also blame it on the lack of proper fantasy in my dreams. I think, that because my dreams have never truly been an escape from anything... that I'm missing something that I'm not supposed to be missing. In other words... "transcendent experience as a fundamental psychological need". And I haven't had any. I am incapable of it.

I've tried writing stories. I've tried roleplaying. I've tried to make myself more comfortable in the body, through actual physical comfort, or from expression of this "otherkin" identity. But nothing seems to help. Nothing actually feels like it means anything. I'm just not getting it.

I just feel trapped. Trapped in this body. Trapped in this reality. I don't know what to do about it. I don't know what I can do about it. I've tried LSD, tried ketamine. I like LSD, and still use it somewhat regularly. But it still doesn't do what I want, or what I need. It's a recreational activity for me, but it doesn't seem to help with anything deep inside.

Stimulants like dexedrine used to help, but every time I try them after a couple months' break, they either barely help at all, or they help for a few weeks and then my tolerance skyrockets.

The depression is the lack of any hope that this will ever change. The depression is this deep discomfort with myself, my body, my life... and the fear that it will be this way forever. That I will never get what I am seeking, and that I will never be able to fix what is broken inside, either.

I've talked to doctors about this, I've talked to therapists about this. I'm getting a neuropsychological evaluation in a few months. I'm trying to help myself, I just don't know if there is anything left to try. The best I can do is get recognized.

Any thoughts or suggestions would be appreciated, of course.

Are you claiming that there is a soul? Becauae many posit that the brain and thus our experiences are made of matter and energy and as mechanistic as anything else.

I don't know if I got any chemical benefit from subsequent use, other than fun (with the consistently worsening serotonin crash afterwards). But just being able to step outside my usual angsty 19-year-old brain for a few hours had a profound effect.

Although I do know people who are clinically depressed, and the hangover/crash doesn't bother them as much, because it's their normal state anyway.

However, insofar as fun is synonymous with happiness, which is antonymous with depression, every cure for depression involves the end goal of fun - one way or another. Pharmaceutically / chemically, emotionally, socially, intellectually, spiritually, you-name-it.

Therefore, regarding this topic, I was positing that, where usage of recreational drugs as a novel cure for depression is concerned, the fun is the curative. But I can see how my generalisation could be interpreted as minimalising, if viewed as a pithy solution precluding all nuance - which it was not intended as!

Granted, I never did it in a quiet "therapeutic" environment, I would have thought of it as a waste because I considered the music and dancing an integral part of the experience, it's a pretty recreational and hedonistic substance after all.

It's not that surprising that if you only use it to "rave for hours" and "open the door for other chemical drugs", then you'll find it a "recreational and hedonistic substance". That's practically a tautology.

"“Enlightenment in a pill,” many have pointed out, is a quintessentially American concept. Who’s got time for all that prayer and study and meditation and practice when there’s an easier, faster way?

But there isn’t. Therein lies the great danger of LSD and its dopey cousin, marijuana. By offering a simulacrum of spiritual and intellectual growth – a very convincing simulacrum at times – it takes you everywhere except where you need to be, which is doing the long, hard work of learning to live."

I resonate with what he says because, like the author mentions later on, I also have many friends who went deep into the psychedelics journey while claiming it was 'freeing their minds', 'enlightening' them, or whatever other concept they liked to use, only to end up, a decade or two later, in either a regular struggling life like so many others, or a downright bad place. I'm probably wrong to generalize, as I'm sure it can help many, but the drugs still can't substitute the individual's effort and struggle to grow, and overcome, and the learning of how to live a meaningful life.

It isn’t like they transform into the ubermensch and transcend the bodily functions of eating and shitting. At the end of the day we all have insecurities

You can be struggling, you can be in a bad place, but that’s orthogonal to feeling connected and spiritually awake

And I’m not saying drugs are how you can (or should) get there, just that the material conditions that someone is living in have nothing to do with being “there”

And by “there”, I mean a sense of abandonment of self to the fabric that you arose out of. Which is not the same thing as conformity, more like a sense of understanding and acceptance of where you belong in the grand scheme of things

It's rather shocking to someone who's not familiar with the inner workings of the pharma industry and medicine in general.

In particular in psychiatry, we have working theories about how the various agents work to achieve anti-depressive or anti-psychotic effects, which are taken as the gospel or proven fact. And then those models turn out absolutely wrong. And we have to face the fact we're prescribing drugs to sick people we have no clue how and why they work. And whether they work at all, often.

It's especially the case when a given drug must be taken for months before any effect is seen. It's essentially impossible to control for other variables over MONTHS of someone's life. You can easily convince them they feel slightly better now because they've been months on end taking Zoloft. They may've easily been better if they hadn't taken it.

There's no vast conspiracy here (well, sort of), but a simple principle: anything that is demonstrable to be USEful, is demonstrable to be abUSEable. No one is restricting homeopathic remedies, they don't have side-effects, or drug interactions, and that's because they don't do anything.

Many antidepressants also don't require too strict of a regime, that's because they actually have very poor therapy effects overall, but even when they do, their effect and side-effects are so stretched out in time, it's very hard to show a hard cause-effect relationship. Despite reading the list you see all sorts of conditions on a drug that may occur as a side-effect, often many of those just occurred during a study, but had little relation to a drug, while other effects were underreported (say often around sexual function as people are embarrassed, or things people can't feel, and aren't tested about, things which doctors don't expect they need to check).

So basically "long-running drugs" are a big question mark, and often turn out to be garbage.

But stimulants like Ritalin, Adderall, Vivanse, Concerta and so on are known to instantly alleviate a number of symptoms of ADHD, depression and so on. Not in months. But within AN HOUR of taking a pill. You can immediately see how it works. But of course you can abuse them, and your body craves them over time, because the body and mind adapts to everything, that's the whole point of homeostasis. So they're restricted and you're told they're not good for you because they can be abused. But this cause-effect relationship is only visible because their effect is also apparent. Not just to medicine, but also to your own body. Your mind makes the cause-effect relationship "this makes dopamine good, circuits work better, take again".

But the fact of the matter with drugs is they're all poison, and the therapeutic effect is in the right dose and application. There's no way around it. If it was nice and fun at any quantity, it's at best just sugar, or at worst some random chemical that few bad studies pushed through, which doesn't at all act like it's supposed to.

This doesn't apply just to stimulants. I have issues with my circadian rhythm so I found a brand of melatonin of Jamieson that is 10mg, slow release. I notice on the first night it works. Other smaller doses from random supplement companies did nothing, heck who knows if they even had the active ingredient.

So I'm in EU. And lo and behold, the EU notices melatonin is USEful at dose over 3mg. Therefore also abUSEable, and has side-effects in some. Very minor I might add.

But it was immediately pulled from shelves, so a long and tedious registration can begin for it as a medication rather than a supplement, and until then, EU people who need it are screwed I guess. It's absurd, but it follows the principle that if it works, it becomes controlled. So the irony in all this is that we have easiest access to garbage that doesn't help, and the drugs that do help, have high prices and restricted access due to over-regulation.

One of those things of the modern world.

Similarly, I bet that if you gave psilocybin to someone under anesthesia, they wouldn’t get the same benefits as someone who took it while awake.

Ruling out the general anesthesia as having an effect because general anesthesia without expectation of depression improvement doesn't improve depression seems like it toys with a false negative in ignoring the possibility of combined factors (specifically psychological disassociation plus expectations of change).

Always thought that was a pretty funny line

No wonder you had a bad trip, although I have absolutely 0 idea about those drugs or their combined effect on one's mind.

The paramedics/doctors I used to work with would administer ketamine from time to time, but they would always pair it with this other drug (maybe midazolam? I don’t quite remember), for the sole purpose of preventing hallucinations.

They made it very clear that the only reason for this mix was that ketamine hallucinations of that dose are often violent or sexual or both, and you don’t want to deal with those kind of allegations.

I personally tried low dose pure ketamine (intramuscular) and it was quite pleasant.

https://www.sciencedirect.com/science/article/pii/S000709121...

The confidence interval in the new study includes zero, although the average beneficial effect is still surprising when considering the usual expected negative effects. I suspect that the real effect may simply be that general anaesthesia causes a susceptibility to suggestion.

It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system.

Very much this! Additionally when discussing ketmaine it's method of action (NMDA receptor antagonist) specifically could be disrupted by the effects of another anesthetic compound.

Just no comparison.

You can see and hear things that aren't there. Even have a conversation with mythical, religious, or spiritual entities.

You can experience 'past lives' (whether factual or not, which I don't believe so, experiencing something you THINK is a past life is interesting).

And it can go south with disturbing or dark imagery.

The placebo effect is a major part of the effect of SSRI, which only improve 1 in 6-8 patients if you subtract the placebo effect [1].

The "number needed to treat" (NNT) mentioned below is the average number of patients that need to recieve the treatment for one of them to be in a better condition than if all of them had recieved a placebo.

1. https://www.cambridge.org/core/journals/psychological-medici...

From my understanding, the experience is very close to DXM (dextromethorphan) from cough syrup, like Robitussin DM. It's a disassociative anesthetic, so my understanding is that you will have feelings and thoughts arise, but be able to examine them "from a distance", as far as being disconnected from them and able to be more objective. I'm really excited to try it, I've had anxiety since 1999, have been given so many different drugs, and have been through biofeedback, cognitive therapy, as well as more new age treatments like meditation. If this doesn't work for me, my next step is probably microdosing psilocybin, but that carries a little bit of legal risk right now (where I'm located).

Ketamine was the only drug I tried (administered during a surgery in my teens) that made a huge impression on me. Everything else I tried later was frankly a disappointment.

* benzos counteract K

* I always assumed therapeutic doses would embrace the K-hole (at which point, IME, you're so detatched that terror isn't really an option any more)

How about randomizing between ketamine and some other drug that makes people trip?

At a certain point you have to wonder if any sufficiently trippy experience helps with depression, anesthesia included.

https://www.independent.co.uk/business/sir-keir-starmer-reve...

Religion wraps it all up in a nice package, and plenty of folks do still choose religion and reap plenty of benefits from it, but there are other options out there.

When I was in my twenties and early thirties, I never worried about any of this at all.

Closed a loan? That costs me points, somehow.

Dad got a new cell phone and they ran the wrong person's credit? That cost me points too, because clearly their screw up was my fault. Hope he was still approved.

I rent and the cars are old. Sometimes I feel like I play on hard mode by having a $3000 VISA as my only debt.

If I make a $2000 purchase, they report it Tuesday, I pay that back to them Thursday, and I check my score? Woah, dropped 80 points! What a delinquent!

That might have become more of a rant than I intended. I should probably just apply for more credit stop the large points changes like this.

Of course, hoping for change and actually changing yourself are two very different things.

https://ketamine.games

It's totally free, private, with no tracking analytics, and many Reddit users have reported increased success using.

> On your Android device, open Chrome Chrome

There was an arc where House was administered ketamine as part of a treatment for his leg and he started walking without his cane, suggesting that his condition was being caused by psychological trauma long after his leg had physically recovered.

I get this. Especially rating emotions 1 to 10 etc.