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.
Comparable studies
Other observational and cohort studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Dynamic coupling of whole-brain neuronal and neurotransmitter systems Healthy humans | 2020 | Observational study | |
| The Serotonin System and Spiritual Experiences Normal male subjects, ages 20-45 years | 2003 | Observational cohort | n = 15 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 15
- Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats Molecular Psychiatry October 21, 2024
- Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms. Psychopharmacology 2023
- Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives ACS Chemical Neuroscience June 6, 2025
- An international mega-analysis of psychedelic drug effects on brain circuit function Nature Medicine April 1, 2026
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
and 10 more in the library
Cites 48
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
and 43 more in the library