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

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...

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Veröffentlicht in:Neuropsychopharmacology (New York, N.Y.) Jg. 44; H. 7; S. 1328 - 1334
Hauptverfasser: Madsen, Martin K, Fisher, Patrick M, Burmester, Daniel, Dyssegaard, Agnete, Stenbæk, Dea S, Kristiansen, Sara, Johansen, Sys S, Lehel, Sczabolz, Linnet, Kristian, Svarer, Claus, Erritzoe, David, Ozenne, Brice, Knudsen, Gitte M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Nature Publishing Group 01.06.2019
Schlagworte:
Adult
Benzylamines
Brain - drug effects
Brain - metabolism
Brain research
Carbon Radioisotopes
Drug dosages
Female
Hallucinogens - pharmacology
Health care
Humans
Intervention
Male
Medical imaging
Mental disorders
Phenethylamines
Plasma
Plasma levels
Positron emission tomography
Protein Binding
Psilocybin
Psilocybin - blood
Psilocybin - pharmacology
Psychedelic drugs
Psychologists
Questionnaires
Receptor, Serotonin, 5-HT2A - metabolism
Scanners
Serotonin
Serotonin 5-HT2 Receptor Agonists - pharmacology
Serotonin S2 receptors
ISSN:0893-133X, 1740-634X, 1740-634X
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Zusammenfassung: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 [ C]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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0893-133X
1740-634X
1740-634X
DOI:10.1038/s41386-019-0324-9