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Neuropsychopharmacology. 2019 Jun;44(7):1328-1334. doi: 10.1038/s41386-019-0324-9. Epub 2019 Jan 26.

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

Author information

1
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark.
2
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
3
Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
4
PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark.
5
Department of Medicine, Psychedelic Research Group, Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Imperial College London, London, UK.
6
Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
7
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, 2100, Denmark. gmk@nru.dk.
8
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark. gmk@nru.dk.

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 stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between 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 percent 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 modeled 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. 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 psychedelic experience.

PMID:
30685771
DOI:
10.1038/s41386-019-0324-9

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