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Alterations in glutamate and the experience of ego dissolution with psilocybin

nature.com

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

#111

Post by caycep »

skohan wrote: post #33
presiozo wrote: 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…

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.

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

#112

Post by flatline »

kortex wrote: post #77
skohan wrote: post #33

Earlier quoted context omitted.

> 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…

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.

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.

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

#113

Post by dahfizz »

ketamine__ wrote: post #20
themgt wrote: post #7

Earlier quoted context omitted.

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 scienti…

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…

> 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.

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

#114

Post by specialist »

elbear wrote: post #98
specialist wrote: post #50

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…

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. :)

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

#115

Post by PragmaticPulp »

themgt wrote: post #7
Etheryte wrote: post #4

Earlier quoted context omitted.

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 scienti…

> 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.

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

#116

Post by WalterSear »

vajrabum wrote: post #107
pharke wrote: post #88

Earlier quoted context omitted.

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 a…

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.

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

#117

Post by amanaplanacanal »

crisissolution wrote: post #59
joeberon wrote: post #6

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 w…

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 b…

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.

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

#118

Post by WalterSear »

stallmanite wrote: post #108
bluntfang wrote: post #56

Earlier quoted context omitted.

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.

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

#119

Post by PragmaticPulp »

stared wrote: post #34

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 o…

> 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.

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

#120

Post by PragmaticPulp »

raducu wrote: post #69
joeberon wrote: post #6

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 w…

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, o…

> 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.

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