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self_made_human  amaratvaṃ prāpnuhi, athavā yatamāno mṛtyum āpnuhi  4mo ago (open.substack.com)   1511 thread views

A Depressed Shrink Tries Shrooms

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This is a first-person account from a psychiatry resident (me) enrolling in a clinical trial of psilocybin. Somewhere between a trip report, an overview of the pharmacology of psilocybin, and a review of the clinical evidence suggesting pronounced benefits for depression.

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There's an endless list of substances that, if used recklessly or without sufficient knowledge, lead to harm.

And very few of them are tempting to use in such ways. Those substances doctors have in fact used in harmful ways. The US just recently had a dustup about opioids.

That would entail a full lecture

It really shouldnt. Listing of the action mechanisms of those drugs is not an explanation - if thats all you would do, the high-level answer is "its just a coincidence". It doesnt explain why no non-recreational drugs do the same. If there is some receptor pathway that necessarily connects the curative and recreational parts, then what makes you think they are distinct?

And very few of them are tempting to use in such ways. Those substances doctors have in fact used in harmful ways. The US just recently had a dustup about opioids.

I bear no responsibility for any that, but leaving that aside, there's an opioid epidemic. If there's a Magic Mushroom epidemic, it must be endemic to Burning Man.

It doesnt explain why no non-recreational drugs do the same.

That's dead wrong. There are all kinds of drugs that have ~nil recreational value, but which engender physiological or psychological dependence.

A non-exhaustive list would include SNRIs, clonidine, gabapentin and pregabalin, corticosteroids, laxatives, nasal decongestants.

These are all substances that the body, once accustomed to, complains quite loudly and painfully about letting go of.

but leaving that aside, there's an opioid epidemic.

Yes. It would be nice to notice danger before it leads to an epidemic. Theres even this same "the numbers say addiction is rare" used as part of the argument for expanding use that far in the first place. You may not be in America, but its relevant because you lean on "we as doctors".

There are all kinds of drugs that have nil recreational value, but which engender physiological or psychological dependence.

I know. What Im talking about is the pattern with psilocybin, ketamine, maybe ecstasy? where they are supposed to treat depression with few sessions, and effects lasting months. Its weird that we found three recreational drugs from different families doing this, and no non-recreational ones.

Ketamine vs LSD/psilocybin are very different in terms of pharmacology, even if the net effect on depression is the same. The former acts by modulating NMDA primarily, the latter 5HT2A.

Subjectively, a k-hole is light years apart from psychedelics.

They then tend to increase neuronal plasticity, via different mechanisms of action.

Its weird that we found three recreational drugs from different families doing this, and no non-recreational ones.

Well, ECT and transcranial magnetic stimulation use no drugs at all (barring incidental anesthesia and muscle relaxant in the former). They also, after a few sessions, relieve depression for months or years. Once again, the terminal effect is believed to be increased synaptogenesis/plasticity. ECT has been around for 70 years.

There's nothing particularly weird about it. The regulatory environment just became somewhat more friendly towards exploring less conventional therapies when the anecdotal evidence became strong enough.

Personally, I couldn't care less how "weird" this seems in the first place, as long as the treatments work. The human body is weird and unintuitive in the first place.

Personally, I couldn't care less how "weird" this seems in the first place, as long as the treatments work. The human body is weird and unintuitive in the first place.

I care about weirdness because its a sign were missing something. This kind of weirdness is not about violating how we expect things to work, you could substitute most properties for "recreational" and it would still be weird. So I dont think it matters whether the body is intutive. By analogy, the current best proof of the four colour theorem works by proving all graphs countain one of 633 possible configurations, and brute-force checking that each of them is reducible in a certain sense, which they all are. You dont need to know anything about mathematics to see that there might be more going on there.

Well, ECT and transcranial magnetic stimulation use no drugs at all

Thats certainly interesting. Even after years of reading Scott, I still had the impression that after the SSRIs, its maybe MAOIs and then nothing. Its still interesting that its only recreational drugs so far. I think cerebrolysin was supposed to be that, but it doesnt seem like that went anywhere.

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