Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans
Dea Siggaard Stenbæk, M. Madsen, Brice Ozenne, Sara Kristiansen, Daniel Burmester, David Erritzøe, Gitte M. Knudsen, Patrick M. Fisher
Journal of Psychopharmacology October 8, 2020 DOI: 10.1177/0269881120959609 via OpenAlex
Summary
AI-generated from the abstractPeople with higher levels of serotonin 2A receptor (5-HT2AR) binding in the neocortex before taking psilocybin experienced shorter peak psychedelic intensity and a longer time to return to normal consciousness. Higher pre-drug 5-HT2AR binding also predicted lower scores on a measure of mystical-type experiences. The findings reinforce that individual differences in brain 5-HT2AR levels shape the temporal and subjective features of the psilocybin experience.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy individuals |
| Intervention | Psilocybin |
| Dose | 0.2–0.3 mg/kg |
| Duration | Single session, with subjective drug intensity assessed every 20 minutes and retrospective questionnaire at session end |
| Topics | Psilocybin Serotonin |
| Keywords | Psychology Hallucinogen Neuroscience |
| Citations | 81 |
| Key finding | Higher neocortex 5-HT2AR binding predicted shorter peak plateau duration, longer return to normal consciousness, and lower mystical experience scores after psilocybin. |
Abstract
Background: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness. Aims: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals. Method: Sixteen participants completed a pre-drug [ 11 C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2–0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models. Results: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score. Conclusion: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.