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

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TLDR
In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotics risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol.
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. Language: en

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References
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Schizophrenics show spatial working memory deficits.

TL;DR: It is demonstrated that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys, and that this deficit is modality independent.
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The Mechanism of Action of Novel Antipsychotic Drugs

TL;DR: The chief evidence for this position is that clozapine (CLOZ) does not differ from typical antipsychotic drugs in these regards but is more effective than typical neuroleptic drugs.
Journal ArticleDOI

Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens

TL;DR: Results indicate that an important component of the mechanism of action of LSD and the phenylisopropylamine hallucinogens is through stimulation of brain 5-HT2 receptors, and supports previous suggestions to this effect.
Journal ArticleDOI

Alterations in the cortical serotonergic system in schizophrenia: A postmortem study

TL;DR: In this paper, the authors characterized various components of the 5-HT system in 14 areas of the frontal and parietal cortex in tissue obtained at postmortem from aged chronically hospitalized nonsuicidal schizophrenics compared to age-matched controls.
Journal ArticleDOI

5-HT receptors: subtypes and second messengers.

TL;DR: Three main families of 5-HT receptors, of which subtypes have been described, are now accepted, and heterogeneity is further substantiated by the cloning of the cDNA's of three different 5- HT receptors.
Related Papers (5)
Trending Questions (2)
What psilocybin and dopamine?

Psilocybin is a hallucinogenic substance that produces a psychosis-like syndrome in humans. The paper suggests that psilocybin-induced psychosis is due to serotonin-2A receptor activation, not dopamine stimulation.

What does psilocybin do to neurons?

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.