open.substack.com
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.
Jump in the discussion.
No email address required.
Notes -
IDK, this "Drugs are actually, like, medicine, maaan" has been around for a while, and generally dont seem like someone youd want to end up as. Its getting "scientific" now that the taboo has weakened, but... no shit it looks promising, youre literally trying drugs for mood. If the researcher cant make that look promising, how on earth did he get a PhD?
It also seems like theres some disorder in your post. The last paragraph before "The aftermath:" for example has a lot of redundancy and sounds like it was supposed to be before those other instances. I thought the part about pharmacokinetics was double as well, only realised now that one is about the nausea and one the whole thing.
Is this a serious critique? Like, do you think that psychiatry of all professions isn't aware of the difference between "feeling happy" and "not being depressed"??
The scientists and doctors performing the studies are well aware that many drugs cause temporary and transient elevations in mood. Far fewer cause lasting improvements.
Prescribing cocaine and heroin is, unfortunately, not a viable cure for depression. Just making someone feel euphoria shortly after taking a drug isn't a "cure" or even a treatment.
I don't blame you, because the psychopharmacology is a lot of receptor names and binding sites that sound almost the same and vary in the last few letters or numbers.
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.
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.
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".
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.
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.
Yes, thats the point. The value of the cliche depends on not thinking you can outsmart it.
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?
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.
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.
That would entail a full lecture on pharmacokinetics, receptor binding, neurotransmitters and so on.
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.
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?
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.
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.
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".
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.
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link
More options
Context Copy link