
Alterations in glutamate and the experience of ego dissolution with psilocybin - kjeetgill
https://www.nature.com/articles/s41386-020-0718-8
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presiozo
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.

~~~
skohan
> 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.

~~~
kortex
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.

~~~
pharke
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.

~~~
vajrabum
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?

~~~
WalterSear
They don't.

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

~~~
pas
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?)

~~~
WalterSear
* 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.

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joeberon
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

~~~
specialist
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.

~~~
josephpmay
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"

~~~
joncrane
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.

~~~
specialist
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.

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stared
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...](https://www.amazon.com/Realms-Human-Unconscious-Observations-
Research/dp/0285648829)) - 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.

~~~
higginsc
> 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/](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]

~~~
KingFelix
also MAPS,

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colordrops
> 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?

~~~
kaikai
Eat mushrooms, apparently.

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Dumblydorr
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.

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carapace
"Set and Setting"
[https://en.wikipedia.org/wiki/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.)

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

~~~
troughway
Would IF help?

