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Comment by Gatsky | Hacker News Reader

The study was just published in the most prestigious medical journal in the world [1].

Whatever you think of the study, this is rather significant. If you told me even 2 years ago there would be a randomised trial of magic mushrooms in NEJM, I would not have believed it for even a second.

One point not to miss is that they screened 1000 patients to come up with the study population of 59.

Nevertheless, I consider the study result quite promising, considering patients only had 2 doses of psilocybin.

[1] https://www.nejm.org/doi/full/10.1056/NEJMoa2032994

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Due to the stigma of psychedelics, there has been a long gap in research, which may have started with 1962 "Good Friday Experiment"

> Almost all of the members of the experimental group reported experiencing profound religious experiences, providing empirical support for the notion that psychedelic drugs can facilitate religious experiences. One of the participants in the experiment was religious scholar Huston Smith, who would become an author of several textbooks on comparative religion. He later described his experience as "the most powerful cosmic homecoming I have ever experienced".

https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment

For a complete story about psychedelic research I recommend “How to Change Your Mind” by Michael Pollan.

"If you told me even 2 years ago there would be a randomised trial of magic mushrooms in NEJM, I would not have believed it for even a second."

In a lot of ways, that's completely depressing for how slowly we've come as a species.

Wait until you learn some history about how regressed!

I agree wholeheartedly, Mister ButtSpark69. For all our civilization's progress, we still have so far to go.

Maybe some mushrooms could help you with that

"The species" has been using psychedelics in religious ceremonies for a long time. We're just out of the loop.

> "The species" has been using psychedelics in religious ceremonies for a long time.

Arguably for thousands of years, as well.

>they screened 1000 patients to come up with the study population of 59

Note that while not ideal this is completely normal for any early stage drug trial. Most drugs get licenced based on data in which the trials would have excluded 90%+ of the typical clinical population. This is certainly true in depression where most drug trials will exclude patients with comorbid MH conditions, and often exclude them for "too many previous episodes". But it's also true in physical health (e.g. asthma).

I'm sure it's even harder when recruiting for an RCT in psychedelics though. A friend was working on clinical applications of MDMA about 15 years ago and a stipulation of the ethics board was that her participants had to have taken MDMA at least 3 times before, but not more than 10 times. Not easy to recruit for that study!

2 doses of psilocybin, vs 6 weeks of SSRI's..! They also seem to cite a big difference in lasting happiness, altough that wasnt the focus of the study.

You can clearly see why psilocybin is illegal. Follow the money... I hope one day the companies and people behind this will go to jail.

And some folks have a really tough time coming off SSRIs too, with bad withdrawal symptoms (extreme anxiety, panic attacks, tremor, hallucinations, memory loss, confusion...) even when tapering over several weeks.

The definition of treatment resistant depression is one of the filters that narrows down the list. A subject must have tried at least two different antidepressants for a certain length of time and within the last few years, in addition to therapy. So, someone who has taken antidepressants for years doesn't automatically qualify.

This is crazy. It's like cart manufacturers lobbied government that anyone who want to buy a car would first have to use a horse and a cart and only be allowed to buy a car if the cart and a horse causes significant problem. Am I the only one seeing corruption here?

If your attempted argument is "X helps people who are not helped by other existing treatments", then limiting your selection criteria to those who have tried several existing treatments and not found success seems to follow logically.

(Though the study's construction seems to fail at that argument, since the claim is that all patients, both those given the psilocybin and those given the SSRI, improved markedly.)

When I wrote that, I had in mind a situation in my country that you can be eligible for private medical cannabis prescription if you try at least two other treatments and you find them ineffective. On the surface it doesn't sound too sinister, but for example, when it comes to chronic pain the drugs that are being given are simply nasty. I still have nightmares about the side effects that I experienced (vivid hallucinations, suicidal thoughts, derealization and more). Given how ubiquitous cannabis is, people with various problems often find, including chronic pain, that it helps massively and unfortunately they cannot bypass going through hell just to get prescription for what helps. They cannot even suggest that they look for medicinal cannabis as they still may be branded as drug seekers and be denied treatment altogether.

I can understand the basis for those requirements in general (e.g. for antidepressants, doctors generally won't start you with an MAOI or a TCA, they'll start you with an SSRI or SNRI or similar, then try another one if that doesn't work, then maybe resort to TCAs if a couple of those don't work, then maybe try an MAOI if a couple of _those_ don't work), though I would agree that having a hard requirement of trying several other drugs first with the toxicity profile of cannabis seems...overly harsh at best. (Especially labeling people drug seekers for it - though they might be gun-shy after the fun with opioids and worried about finding a new epidemic of cannabis addicts, which seems...unlikely.)

Studies are being designed to reduce the possibility that a patient just didn't respond well to one medication but instead shows a general lack of improvement from antidepressants. The goal is to know that the patient improved from psilocybin, specifically. One other problem with this stacked definition of treatment resistance is that doctors are going to be coerced to always try multiple antidepressants and guinea pig the hell out of patients. Doctors are going to refuse initial psilocybin treatment and only use it as a last resort because the studies are going to show that treatment resistance is necessary. Even worse will be if doctors are coerced by regulators and medical institutes to strictly follow their protocol. And this only includes doctors who agree to add psilocybin to their treatment programs. A lot of doctors will resist using it, claiming "unearned wisdom is dangerous wisdom" and so forth. The "unearned wisdom" claim is based on the indoctrinated belief that a patient must undergo many hours of therapy and slowly peel layers of experience in order to truly understand, whereas psilocybin offers a shortcut.

For these reasons and others, I believe that the vast majority of depressed people who haven't healed from traditional methods ought not pursue clinical studies as a viable pathway to psilocybin-assisted therapy.

"One point not to miss is that they screened 1000 patients to come up with the study population of 59."

I'd be curious how many 10,000s if not 100,000s of people pharmaceutical companies go through, along with changing/crafting their selection criteria to keep out people/symptoms they know have more/strong "side"/harmful effects with, until they get acceptable looking results; propaganda using truth - "Misleading with true fact" - https://www.youtube.com/watch?v=lls_2tfWcUI

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