Psilocybin

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

This single-blind study (n=8) provides the first report of the positive correlation between the intensity of psychedelic effects, cerebral occupancy of the 5-HT2A receptor, and plasma psilocybin levels in humans after a single dose of psilocybin (3-30mg).

Authors

  • Gitte Knudsen
  • Patrick Fisher

Published

Neuropsychopharmacology
individual Study

Abstract

The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through the stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin’s active metabolite, psilocin. We here report for the first time the relationship between the intensity of psychedelic effects, cerebral 5-HT2AR occupancy and plasma levels of psilocin in humans. Eight healthy volunteers underwent positron emission tomography (PET) scans with the 5-HT2AR agonist radioligand [11C]Cimbi-36: one at baseline and one or two additional scans on the same day after a single oral intake of psilocybin (3-30 mg). 5-HT2AR occupancy was calculated as the per cent change in cerebral 5-HT2AR binding relative to baseline. Subjective psychedelic intensity and plasma psilocin levels were measured during the scans. Relations between subjective intensity, 5-HT2AR occupancy, and plasma psilocin levels were modelled using non-linear regression. Psilocybin intake resulted in dose-related 5-HT2AR occupancies up to 72%; plasma psilocin levels and 5-HT2AR occupancy conformed to a single-site binding model. The subjective intensity was correlated with both 5-HT2AR occupancy and psilocin levels as well as questionnaire scores. We report for the first time that intake of psilocybin leads to significant 5-HT2AR occupancy in the human brain and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience. Important for clinical studies, psilocin time-concentration curves varied, but psilocin levels were closely associated with the psychedelic experience.

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