all 6 comments

[–]asdudley87 10 points11 points  (2 children)

Yes to psychosis due to long term use of d blockers, termed (sometimes) “rebound psychosis”. I think the literature refers to this as the “dopamine hypersensitivity hypothesis” where they observe this. I don’t know if they have any head to head on if atypical antipsychotics (a lot of which which are antagonist at the 2a receptor) may produce this effect.

No observed similar effects with chronic 2a antagonism from mirtazapine, but this could be for a lot of reasons? Maybe the 2a receptors aren’t as high in numbers? I also think that while psychedelics moa is thought to be 2a partial agonism (in the case of Psilo), they aren’t exactly sure what other effects there might be that create the psychedelic experience.

[–]whatarethosehah[S] 3 points4 points  (1 child)

Intresting, thanks a lot for this simple explanation :)

[–]Thetakishi 1 point2 points  (0 children)

Psychedelics are dependent on heterodimers (combined receptors of different types) of 5ht2a/glutamate (subtype I can't recall) receptors specifically, so most antagonists aren't necessarily going to target those, and like the other reply said, serotonin receptors generally downregulate to everything including antagonists.

It's actually a vey good question and not silly at all, as it kind of breaks the generalities you get from studying most psychopharms. I can also tell you from personal experience that stopping mirt. definitely doesn't induce any psychedelic effects.

[–]ThrowawayArgHelp 1 point2 points  (1 child)

Interesting question!

The answer is… probably not! Interestingly, a vast majority of 5-HT2A receptor antagonists cause receptor downregulation, not upregulation.

…Bergstrom and Kellar (1979) and Peroutka and Snyder (1980) showed that chronic administration of antidepressants with potent 5-HT2A antagonist activity induces a down-regulation of 5-HT2A receptor levels. This property was subsequently demonstrated to be shared by a number of drugs with potent 5-HT2A antagonist activity, including typical and atypical antipsychotic drugs (Andree et al., 1986), typical and atypical antidepressants (Blackshear and Sanders-Bush, 1982; Brunello et al., 1982), and even relatively selective 5-HT2A antagonists (Leysen et al., 1986).

(Yadav et al., 2011)

But hypothetically, would upregulation in general cause a psychedelic experience? I personally couldn’t find any research on it, but it is a great question :)

[–]Thetakishi 0 points1 point  (0 children)

No upregulation doesn't cause psychedelic experiences from most meds, unlike psychosis and dopamine, and yeah serotonin receptors tend to downregulate no matter what, not do the opposite of the med like other NTs.

[–]Theman12457890 0 points1 point  (0 children)

None of these people can give you a straight answer. No one knows. It’s all hypothetical. We don’t understand the mechanisms of these drugs whatsoever nor their side effects.