Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation
Yun Zhou, Frederick S. Barrett, Theresa M. Carbonaro, Joshua Roberts, Gwenn S Smith, Roland R. Griffiths, Dean F. Wong
Frontiers in Neuroergonomics January 20, 2022 DOI: 10.3389/fnrgo.2021.784576 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Dose | 10 mg/70 kg |
| Topics | Default mode network Psilocybin Serotonin |
| Keywords | Radioligand Hallucinogen 5-HT Receptor Occupancy Inverse agonist Resting State FMRI |
| Citations | 17 |
| Key findings | Oral psilocybin at 10 mg/70 kg produced an average 39.5% occupancy of 5-HT 2A receptors across cortical regions, with highest occupancy in default mode network areas. |
Abstract
Psilocybin (a serotonin 2A, or 5-HT 2A , 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-HT 2A receptor inverse agonist radioligand [ 11 C]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-HT 2A receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). Average 5-HT 2A 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-HT 2A receptor occupancy.