Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation

Frederick S. Barrett; Frederick S. Barrett; Yun Zhou; Theresa M. Carbonaro; Joshua M. Roberts; Gwenn S. Smith; Gwenn S. Smith; Roland R. Griffiths; Roland R. Griffiths; Dean F. Wong

doi:10.3389/fnrgo.2021.784576

Frontiers in Neuroergonomics (Jan 2022)

Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation

Frederick S. Barrett,
Frederick S. Barrett,
Yun Zhou,
Theresa M. Carbonaro,
Joshua M. Roberts,
Gwenn S. Smith,
Gwenn S. Smith,
Roland R. Griffiths,
Roland R. Griffiths,
Dean F. Wong

Affiliations

Frederick S. Barrett: Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Frederick S. Barrett: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Yun Zhou: United Imaging Intelligence, Shanghai, China
Theresa M. Carbonaro: Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Joshua M. Roberts: Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Gwenn S. Smith: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Gwenn S. Smith: Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Roland R. Griffiths: Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Roland R. Griffiths: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Dean F. Wong: Departments of Radiology, Psychiatry, Neurology, and Neuroscience, Mallinckrodt Institute of Radiology, Washington University in St Louis, St. Louis, MO, United States

DOI: https://doi.org/10.3389/fnrgo.2021.784576
Journal volume & issue: Vol. 2

Abstract

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Psilocybin (a serotonin 2A, or 5-HT2A, receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. The current report utilized positron emission tomography (PET) with the selective 5-HT2A receptor inverse agonist radioligand [11C]MDL 100,907 (a.k.a. M100,907) and cortical regions of interest (ROIs) derived from resting-state functional connectivity-based brain parcellations in 4 healthy volunteers (2 females) to determine regional occupancy/target engagement of 5-HT2A receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). Average 5-HT2A receptor occupancy across all ROIs was 39.5% (± 10.9% SD). Three of the ROIs with greatest occupancy (between 63.12 and 74.72% occupancy) were within the default mode network (subgenual anterior cingulate and bilateral angular gyri). However, marked individual variability in regional occupancy was observed across individuals. These data support further investigation of the relationship between individual differences in the acute and enduring effects of psilocybin and the degree of regional 5-HT2A receptor occupancy.

Published in Frontiers in Neuroergonomics

ISSN: 2673-6195 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.frontiersin.org/journals/neuroergonomics

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