Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.
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.
Vollenweider
F X
FX
Research Department, Psychiatric University Hospital Zürich, Switzerland.
Vollenweider-Scherpenhuyzen
M F
MF
Bäbler
A
A
Vogel
H
H
Hell
D
D
D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009483:Neuropsychological Tests; D011562:Psilocybin / Q000009:adverse effects*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012016:Reference Values; D012559:Schizophrenia / Q000139:chemically induced*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*
D006213:Hallucinogens; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D011562:Psilocybin; D007650:Ketanserin