Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action
Bäbler, A., Hell, D., Vogel, H., Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I.
This paper (1998) was one of the first to identify psilocybin/psilocin as working on the serotonin (5-HT2A) receptor and not only on the dopaminergic system. The direct comparisons as mentioned in the article are nowadays a bit more nuanced.
Abstract
Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.