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 preprint DOI: 10.21203/rs.3.rs-7469144/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| 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 |
| Topics | Neuroplasticity Psilocybin |
| Key findings | 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.
Comparable studies
Other observational and cohort studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls | 2005 | Observational cohort | n = 20 |
| Neural correlates of attentional expertise in long-term meditation practitioners Age-matched participants including expert meditators and novices | 2007 | Observational cohort | |
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Functional Reorganization of the Default Mode Network across Chronic Pain Conditions Patients with chronic back pain, complex regional pain syndrome, and knee osteoarthritis | 2014 | Observational cohort | |
| State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect Novice meditators | 2016 | Longitudinal study | n = 13 |
Citations in the library
Cites 33
- 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
and 28 more in the library