[tokai]

Literally the last line of the article:

"Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias."

Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.

[mtlmtlmtlmtl]

Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable.

That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.

[tokai]

yes ofc, but if the treatment is the trip it will never work blinding it like this. If anything they should be looking for drugs that give comparable trips, with no potential for depression treatment.

[mtlmtlmtlmtl]

I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to cause trauma.

I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.

[oaktrout]

Small correction, the active ingredient in Salvia is a kappa opioid agonist.

[mtlmtlmtlmtl]

You're right, thanks for the correction! Really should check more of these things and not just do it from memory.

[tpm]

Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect.

No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.

[natechols]

> Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect.

It does, and this observation led to the development of dedicated antidepressant drugs. There are several such cases where interesting side effects turned out to open a world of possibilities, including an anti-TB drug that also led to antidepressants, and of course Viagra.

[tpm]

Yeah, I vaguely remembered something like that. The anti-TB drug is isoniazid/iproniazid which is also a MAO inhibitor.

[Spivak]

You basically can't do science like this and prove anything useful outside of group A is the more effective than group B. And that's assuming your test subjects can't tell the difference. That would tell you that at minimum either A or B has a non-zero effect because they both can't do nothing and be different. But proving that A is an improvement over not A is the important bit. A and B could both be worse than nothing but A is just less bad.

"find something that has a similar trip but does nothing" is actually equivalent to the original problem.

[naasking]

> That line just says people should do better at this in future to get more accurate results

But it's also doubling down on the assumption that the subjective effects aren't the source of the benefit.