Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression | Hacker News Reader

Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression

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43 pointscpncrunch25 comments

I've always wondered if one dose of LSD could have been responsible for a fundamental change in my mind. There were other things of course going on in those college years, but I can say wth certainty that I became a very different person at some point in those early to mid twenties.

It's such that I have wondered if those I know who suffer various emotional issues might not benefit from a hallucinogenic trip—perhaps a rewiring of the mind.

> I can say wth certainty that I became a very different person at some point in those early to mid twenties

Let's be fair, most people do.

It may simply be that the intense disruption of a 5 hour long experience of chemically-induced novel pleasures - in people who'd long forgotten any form of enjoyment at all - while also being under special attention from caring professionals, is Very Nice Indeed. And that very nice experiences are the most direct salve that exists, when it comes to ameliorating a lifetime of unpleasant ones.

"I can say wth certainty that I became a very different person at some point in those early to mid twenties" - not to discount that, but I do suspect many developing adults (LSD or not) might make similar claims about distinct periods of mental change as they work their way into early adulthood.

There’s more evidence it is than it’s not. And, yes, even people who have been super stubbornly against psychedelics only very seldom come to regret taking some. Which you cannot say for other recreational or sedating stuff at all.

According to the GPTs, the LSD ranks the bottom in the chart of ‘damage done to your organism’ while alcohol tops it every time.

While using GPTs to explore my own bias, I liked the re-phrasing "the chemical opens a window so that the profoundly human experience of care, safety, and novel emotion can finally get through to a brain that had walled itself off".

Highlighting how the human experience is an intrinsic part of the benefit seen, but not the only part.

(and I totally agree with you, alcohol is one of the strongest and also one of the less pleasant - both in withdrawal and in long term health impact, not to mention social harm - recreational things that I or people-that-I-know-well have ever tried)

Indeed I suppose many are on the same opinion here… save for some super stubborn uneducated jerks who keep downvoting all my ‘Alcochol-is-likely-worse-than-LSD’ comments without even getting into reasonable argument.

Alcohol is definitely much more dangerous than LSD. The problem is that some people think LSD causes mental illness instead of the truth, which is that mentally ill people seek out substances.

90%+ of schizophrenics smoke cigarettes. Therefore, cigarettes cause schizophrenia. Nobody believes that (I don’t), I’m not sure why they think LSD makes people schizophrenic instead of schizophrenics seeking out LSD.

The opposition you face is purely statistical, based on the fact that alcohol is by far the most commercially successful recreational drug.

When statistics are so biased, quality of objective argument is swamped by simple numbers.

At the same time, using LSD once is higher risk than one night of drinking.

This is absolute nonsense and is not backed by any sane scientific evidence. Using alcohol even once, in the quantities readily made available everywhere where alcohol is available, can finish you off in the most diverse and bizarre ways.

What’s even more ridiculous is the fact even quarter pill of the Xanax kind mixed a very limited amount of alcohol gets you potentially higher than most psychedelics when properly dosed. And both opioids are super well available…

Bit of an aside, but a quarter of Xanax can also immediately take you out of an LSD trip.

That is definitely 100% false. You can drink yourself to death in a night, I almost did. Woke up in the ICU after blacking out with an O2 of 70%.

You have never done LSD so I won’t even bother with my experiences on it other than you don’t lose your sense of reality, risk or self-preservation.

I have friends who have had serious permanent vision changes as a result of taking a reasonable dose of psychedelics one time (which is one of the main reasons I haven't tried it). If you overdose on either lsd or alcohol you'll have serious ill effects.

Vision changes are part of any intoxication, most avid alcohol users have them all the time. You have vision changes due to high blood pressure, so vision is perhaps not a KPI to put on the table as a major one.

Unfortunately life isn’t a triple-bling placebo controlled study.

There isn’t a cohort consisting entirely of otherwise identical yous we can use to retrospectively assess the outcomes of single-changes.

And besides, it’s not like one or any number of psychedelic experiences, results in a perfect human experience free of suffering or what have you.

I could use a triple-bling study...

Every Friday night after work, happy hour starts at 6.

Oh, I wrote “bling” lol

> but I can say wth certainty that I became a very different person at some point in those early to mid twenties.

Early to mid twenties is where people definitely leave their teen years, by definition.

Everyone becomes a different person around this time. Maybe your experience was mixed in there, but becoming a very different person around that age happens to a lot of people without psychedelics.

If you have a messy room, you don't throw a grenade in hopes that after explosion things will end up in "better" places than before.

Hence the wisdom of the 'already been there': (Mind)set and setting.

A 'clinical' environment, may not be the ideal setting for some patients.

I don't think psychedelics are going to be any different to any other officially approved psychiatric medicine - we don't know enough to know which subset of patients will respond well vs. poorly for psychedelics any more than already available FDA approved (or equivalent similar organisations for other nations) of psychiatric medicines, which in some cases fuck people over for life after a single dose. Large numbers of people have permanently suffered a massively reduced quality of life as a result of a single Invega injection, yet it's still administered regardless.

All I know, is that we don't know enough to know enough.

My personal empirical experience is that I'm wired backwards and have atypical responses to what is now available due to the clinical phase 3 trial majority response, and have personally suffered from supposed experts applying the 'approved' treatments. Even my current psychologist admits they're in foggy territory which makes her better than previous medical professionals I've dealt with.

Advances in physiological medicine changes before and during my lifetime have been incredible. Advances in psychiatric medicine during my lifetime have been a result of capitalist companies gaming systems to create revenue streams rather than improve the overall well-being of humans. The war on drugs just stifled understanding of what options are out there, and what cause-effect mechanisms exist.

It's nice to see independent studies above and beyond the other end of the extremists (e.g. MAPS) contributing to understanding, even though sample sizes are miniscule compared to what we need.

We're currently gambling/playing the probabilistic statistic odds on psychiatric medications without knowing the 'why/how' they work.

We still don't fully understand the mechanisms of action of Aspirin which was first synthesised well over a century ago, and been in widespread use for many decades.

I think it's highly dependent on the environment of the trip alongside the reaction. I doubt if they freak out it'll have the same efficacy.

The psilocybin dosage in this study seems to be miniscule (5mg, 25mg), which is fair given its controversial reputation (undeserved IMO) and researchers’ plausible risk aversion. However, to see meaningful improvements in TRD I’d expect larger doses to be necessary for most people.

I'm of the same opinion. Also apparently one recipient ended up with HPPD from this medical study, when they essentially only had 30mg of psilocybin every 6 weeks? I think prior history should be checked there.

> Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder.

The psychotherapeutic therapy probably did the heavy lifting for any positive effects. At least from what I can tell, for depression, the magic of psychedelics is the reckoning you're faced with to clean up your act and think of more than just yourself.

Still, always glad to see more studies on psilocybin!

~2.5g of psilocybe cubensis is considered a standard dose; according to this [0] study, ~10mg/g is a pretty typical psilocybin concentration in mushrooms, so 25mg of pure psilocybin sounds about right.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC11856550/

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