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Alterations in glutamate and the experience of ego dissolution with psilocybin

nature.com

171–180 of 192 posts

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#171
post #33
post #2

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…

> 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!

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#172
post #141

Earlier quoted context omitted.

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?

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." https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...

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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#173
post #77

Earlier quoted context omitted.

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.

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…

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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#174

Earlier quoted context omitted.

> 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 en…

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…

> 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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#175
post #141

Earlier quoted context omitted.

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." https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...

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 ketam…

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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#176

Earlier quoted context omitted.

"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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#177

Earlier quoted context omitted.

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…

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…

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.

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#178
post #156

Earlier quoted context omitted.

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 wha…

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.…

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

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#179

Earlier quoted context omitted.

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?

[deleted]

Re: Alterations in glutamate and the experience of ego dissolution with psilocybin

#180

Earlier quoted context omitted.

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…

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…

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.
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