Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
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Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. / 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.
I: Neuropsychopharmacology, Bind 44, 2019, s. 1328-1334.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
AU - Madsen, Martin K.
AU - Fisher, Patrick M.
AU - Burmester, Daniel
AU - Dyssegaard, Agnete
AU - Stenbæk, Dea S.
AU - Kristiansen, Sara
AU - Johansen, Sys S.
AU - Lehel, Sczabolz
AU - Linnet, Kristian
AU - Svarer, Claus
AU - Erritzoe, David
AU - Ozenne, Brice
AU - Knudsen, Gitte M.
N1 - Correction to: Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels (Neuropsychopharmacology, (2019), 10.1038/s41386-019-0324-9)
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41386-019-0324-9
DO - 10.1038/s41386-019-0324-9
M3 - Journal article
C2 - 30685771
AN - SCOPUS:85061199420
VL - 44
SP - 1328
EP - 1334
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -
ID: 214302750