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Comment by _yb2s | Hacker News Reader

> I think it's possible that the phenomenological experience _is_ the mechanism of action for these substances, that the actual experience of the trip is what makes the difference.

I was really confused about the entire concept of blinding a study like this until I read your comment... Now I realize they are indeed proceeding from the assumption that the phenomenological experience is somehow distinct from the mechanism of action.

That seems really unlikely to me- these drugs are unique because of the phenomenological experience! It seems self evident that this experience is the reason for therapeutic effects.

Imagine the absurdity of trying to design a study blinding the effects of meditation for example. Meditation has measurable benefits, but what are the chances those aren't caused by the psychological effects of experiencing meditation?

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It’s worth trying because it could be that there is a chemical mechanism rather than it being the trip. For example ketamine can ‘cure’ people of alcoholism and depression at doses that do not produce ‘profound’ experiences or at doses that do. Having said that I accidentally had a ‘therapy’ session while completely off my tits on LSD and it helped with things that I’d not previously been helped with on other trips.

The issues at hand are complex, it’s worth trying to control just to find out what the mechanisms are.

Also apologies for all of the air quotes in this ‘comment’

I’ve heard this theory before but wouldn’t that mean you could take these substances while anesthetized and derive the same benefits without remembering any of the “trip”?

It's self evident to you that there's no effect on brain chemistry that accompanies the experience? A change that could have an impact on the condition?

You might be right, maybe you're even probably right, but it's not self evident to me.

“Chemical imbalance” antidepressants take weeks of ~100 milligram tablets to take effect. (Nobody can quite explain what the imbalance was to begin with, and what the ideal levels are…)

Psychedelics have an impact at the microgram range, with a single dose. They could be hundreds of thousands of times more potent, or, it could be the experience.

With MDMA the doses studied aren't that different than the amounts needed for some SSRIs. Not sure what you're going for with the mass of the ingredient.

The point was that they need to be taken for weeks before there’s any improvement. Not so much the size of the dozes.

They have a good point. The whole “chemical imbalance” thing has come under significant scrutiny as of late.

could they give the control group other psychedelics in some of these studies to see if they are differently effective? That could be blinded right?

That would be further down the path.

In this design, I have to imagine both groups' sessions were very much affected by thoughts of "am I about to trip or is this just allergy relief?" To be honest, I am uncomfortable with the thought of a participant being unsure if they had been given a psychedelic.

Consider that a non-trivial number got it wrong! To me that signals some of the control group participants may have been quite agitated.

I wouldn't mind seeing a self-controlled design where participants are randomized to receive either psilocybin with therapy or non-psilocybin therapy first, but ultimately end up receiving both. As others have noted it's not just the drug, it's the drug and the experience of therapy so I think the two ought to be packaged.

Ultimately though, what I am most curious about is the long term sustenance (and/or repeatability) of any effects and also whether any negative effects appear later.

The first wave of psychedelic research also showed some promise, but their utility faded. Have we gotten any better? Six months of alcohol use disorder or depression relief is great and useful, but the goal ultimately is long term relief.

It takes some tens of grams of sodium chloride to significantly alter my body chemistry. A few milligrams of cyanide will alter my body chemistry enough to be measured by the existence of a pulse.

well at least occham's razor is definitely calling buttshit

...or try to study the effects of a university education with a double blind study.

There are probably rules demanding blinding for these studies. Let's hope they don't hold back the research for too long.

Yea ... it's weird to talk to some types of neuroscientists who speak as though a particular neurotransmitter is an actual psychological phenomenon (beyond just short hand, IMO).

So focused they are, it seems, on the therapeutic development angle (receptors, agonists, drugs, etc), that they've forgotten that the brain/mind is a processing network of neurones that can exhibit phenomena of multiple levels of complexity. Sure, a particular neurotransmitter or receptor may be involved in a particular pathway, but that's just signalling, not the process itself, let alone its totality.

https://xkcd.com/1462/

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