Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action
Neuroreport – December 01, 1998
Source: OpenAlex
Summary
A compelling neuroscience finding: the hallucinogen Psilocybin, a psychotomimetic, induces a psychosis-like state resembling Schizophrenia. In a pharmacology study of 25 volunteers, the serotonin-2A antagonist Ketanserin and an atypical antipsychotic blocked it, while the dopamine antagonist Haloperidol intensified it. This medicine insight, vital for Psychedelics and Drug Studies, reveals Psilocybin-induced psychosis stems from 5-HT receptor overactivation, independent of dopamine. Understanding this neurotransmitter receptor influence on behavior could guide Antipsychotic development for Schizophrenia research and treatment.
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.