Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

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.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Psilocybin ↓Opposes

  Psilocybin produced a psychosis-like syndrome that was blocked by serotonin-2A antagonists but increased by a dopamine antagonist, implicating serotonin-2A activation.

  Synthesized October 25, 2026

• State of the evidence: Serotonin ↑Supports

  Psilocybin's psychotomimetic effects were blocked by the 5-HT2A antagonist ketanserin and risperidone but increased by haloperidol, supporting serotonin-2A activation as the mechanism.

  Synthesized October 19, 2026

Comparable studies

Other experimental studies on serotonin, most cited first.