Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action
OrthoEvidence Journal (OE Journal) - ACE Report
OE Journal. 2022;10(10):27 Neuroreport. 1998 23-Feb;():. 10.1097/00001756-199812010-00024What this means for my practice?
The blocking of psilocybin-induced effects by both ketanserin and risperidone illustrate the role that 5-HT2 receptor agonism plays in the psilocybin-induced effects. A 0.25 mg/kg dose of psilocybin produces a psychotic syndrome which includes changes in mood, disturbances of sensory perception and thought processes and impaired ego-functioning. These changes are also observed in patients entering early schizoprenic stages. Psilocybin also produced spatial working memory deficits, similar to those seen in schizophrenic patients. These deficits were completely prevented by 5-HT2 antagonism but not dopamine receptor antagonism, further suggesting evidence for the role 5-HT2 receptor stimulation plays in both schizophrenic symptoms and psilocybin effects. The results are limited by the small sample size.
Study Summary
Twenty-five healthy subjects underwent two within-subjects, placebo-controlled studies to test the role that 5-HT2 serotonin receptors play in the effects of hallucinogens on humans. In group 1 (N =15), there were three pretreatment groups, who were given (5-HT2 antagonist), haloperidol (dopamine receptor antagonist) or risperidone (mixed 5-HT2/dopamine antagonist), respectively. These groups were then given 0.25 mg/kg of psilocybin. The second group (N = 10) received a higher dose of ketanserin and then the same dose of psilocybin afterwards. Note that only results from the second study are displayed here. The APZ-OAV scale was used to measure the effects of psilocybin. Both the ketanserin and risperidone blocked the effects of psilocybin, dose-dependently. Haloperidol increased the effects of psilocybin.
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