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self_made_human  amaratvaṃ prāpnuhi, athavā yatamāno mṛtyum āpnuhi  2mo ago (open.substack.com)   1371 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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Prescribing cocaine and heroin is, unfortunately, not a viable cure for depression.

Has anyone tried? In the manner of these studies I mean, not by just looking at addicts. People whove done heroin generally report that naive use is an experience beyond anything they had before. I would not be surprised if this influences people even months later. But it also might not, there are always those pescy details. E.g. maybe it overlaps too much with the alcohol high to show effects in our society.

Its more that we have now found multiple drugs with different mechanisms of action, but apparently similar in terms of how they are used and effect against depression, and all of them are used recreationally for their short-term effects. That suggests to me that it works off the recreational bit, and it again wouldnt be super surprising if it did. "Drugs can make you feel better when used responsibly" is hardly a new insight - the entire problem is the way they lead to non-responsible use.

Also curious what you think of this one.

Has anyone tried? In the manner of these studies I mean, not by just looking at addicts. People whove done heroin generally report that naive use is an experience beyond anything they had before. I would not be surprised if this influences people even months later. But it also might not, there are always those pescy details. E.g. maybe it overlaps too much with the alcohol high to show effects in our society.

I assure you that they're not effective solutions. Cocaine is highly addictive, and the comedowns more than make up for the very short-term euphoria. Heroin? That's akin to borrowing happiness from tomorrow at a very high interest rate, it doesn't end well.

We've got plenty of studies on the long-term effects of stimulants and opiates. They don't help with depression in any meaningful sense.

"Drugs can make you feel better when used responsibly" is hardly a new insight - the entire problem is the way they lead to non-responsible use.

I've only endorsed psilocybin in a therapeutic, observed context. It's not a particularly habit forming drug. More importantly, it has a short duration of acute effect, while appearing to durably reduce depression for months after a single dose. It's highly reductive to dismiss such advances as "Drugs can make you feel better when used responsibly".

Also curious what you think of this one.

Addictions aren't made alike. Some can be entirely benign, coffee, as Katja intentionally became dependent on, won't kill you, nor will it ruin your psycho-social functioning. ~Nobody has lost their job or family because they drink too much coffee.

Contrast that to becoming a lay-about stoner, a coke fiend, or a heroin addict.

That's akin to borrowing happiness from tomorrow at a very high interest rate, it doesn't end well.

If were talking about the effect of a ~one time experience, then comedowns arent necessarily relevant. We might imagine for example someone seeing "Wow, its possible to be happy" and that giving him hope in life. That hope might point down the abyss, but thats only measurable when you get there.

But taking this at face value: do you think peoples lives are worse for alcohol? Theres a hangover there too, and in the narrow pleasure-pain accounting, youre not coming out ahead - yet there are many apprently non-addicted people who are using it a decent amount.

It's highly reductive to dismiss such advances as "Drugs can make you feel better when used responsibly".

Yes, thats the point. The value of the cliche depends on not thinking you can outsmart it.

Nobody has lost their job or family because they drink too much coffee.

I am well aware. The link is not directly related to my point here, and I was wondering more about the idea that shes better off for it.

It also remains fascinating, the way people will respond to every part of my comment but the main one. Why do you think apparently different drugs work in such similar ways here?

If were talking about the effect of a ~one time experience, then comedowns arent necessarily relevant. We might imagine for example someone seeing "Wow, its possible to be happy" and that giving him hope in life. That hope might point down the abyss, but thats only measurable when you get there.

I think it's been quite reasonably established that the particular drugs you've mentioned so far aren't generally beneficial for depression, be it for a once off dose or on the regular.

There are limited circumstances where stimulants might help, such as in ADHD, where they provide mood benefits and increase functioning. That is not equivalent to endorsing cocaine for depression, it's a shitty choice in that regard. Too euphoric and addictive, wears off too quickly.

Yes, thats the point. The value of the cliche depends on not thinking you can outsmart it.

Are you aware of what doctors generally do? There's an endless list of substances that, if used recklessly or without sufficient knowledge, lead to harm. There's a drastic difference between giving someone opioids to someone in severe pain after a surgery and taking oxy to get high.

I feel no need to belabour that point, you go to a medical professional to get guided, targeted advice even for risky substances.

Why do you think apparently different drugs work in such similar ways here?

That would entail a full lecture on pharmacokinetics, receptor binding, neurotransmitters and so on.

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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