Psilocybin’s effect on human brain synaptic plasticity
Gitte M. Knudsen, Annette Johansen, Pontus Plavén‐sigray, M.k. Madsen, Anna Søndergaard, Catharina Messel, Mark W. Geisler, Arafat Nasser, Drummond E-Wen Mcculloch, Vincent Beliveau, Alexandra Vassilieva, Anton Lund, Szabolcs Lehel, Brice Ozenne, Dea Siggaard Stenbæk, Patrick M. Fisher, Claus Svarer
Research Square October 10, 2025 DOI: 10.21203/rs.3.rs-7469144/v1 via OpenAlex
Summary
AI-generated from the abstractA single dose of psilocybin increases synaptic density in the frontal cortex and hippocampus of healthy individuals, but the magnitude of this effect depends on the environment in which the experience occurs. Participants who took psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density compared to those dosed inside an MRI scanner. These findings indicate that psilocybin's neuroplastic effects are modulated by environmental context, with implications for psychedelic-assisted therapies.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy individuals |
| Intervention | Psilocybin |
| Dose | a single dose |
| Duration | One-week post-dose for PET scans; subjective experiences assessed immediately and at three months |
| Key finding | Psilocybin's neuroplastic effects, measured as increases in synaptic density, are modulated by environmental context, with greater benefits in a therapeutic-like setting than in an MRI scanner. |
Abstract
Abstract Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmen-tal context remain unclear. Here, we tested whether a single dose of psilocybin alters synap-tic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen healthy participants had a psilocybin-induced psychedelic experi-ence either inside an MRI scanner or in a therapeutic-like room. We assessed synaptic densi-ty changes by measuring the Synaptic Vesicle glycoprotein 2A in the frontal cortex and hip-pocampus with [¹¹C]UCB-J PET at baseline and one-week post-dose, and assessed subjective experiences immediately afterwards and at three months. Participants treated in the thera-peutic-like setting exhibited more intense mystical-type experiences, longer-lasting psycho-logical benefits, and greater increases in synaptic density than those dosed in the MRI scan-ner. These findings indicate that psilocybin’s neuroplastic effects are modulated by envi-ronmental context, with important implications for psychedelic-assisted therapies.