[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.