Psilocybin's effect on human brain synaptic plasticity.
Annette Johansen, Pontus Plavén-sigray, Martin K Madsen, Anna Søndergaard, Catharina Messel, Maria Geisler, Arafat Nasser, Drummond E. Mcculloch, Vincent Beliveau, Alexandra Vassilieva, Anton Lund, Szabolcs Lehel, Brice Ozenne, Dea S Stenbæk, Patrick M. Fisher, Claus Svarer, Gitte M. Knudsen
Translational Psychiatry July 15, 2026 DOI: 10.1038/s41398-026-04285-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy individuals |
| Intervention | Psilocybin |
| Dose | 0.3 mg/kg |
| Duration | One-week post-dose for PET imaging; subjective experiences assessed immediately and at three months |
| Topics | Neuroplasticity Psilocybin |
| Registration | NCT03289949 |
| Key findings | Psilocybin's effect on synaptic density is modulated by environmental context, with a therapeutic-like setting associated with greater increases in synaptic density and more intense mystical-type experiences than an MRI scanner setting. |
Abstract
Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmental context remain unclear. Here, we tested whether a single dose of psilocybin (0.3 mg/kg) alters synaptic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen healthy participants had a psilocybin-induced psychedelic experience either inside an MRI scanner or in a therapeutic-like room. We assessed synaptic density changes by measuring the Synaptic Vesicle glycoprotein 2A in the frontal cortex and hippocampus with [¹¹C]UCB-J PET at baseline and one-week post-dose, and assessed subjective experiences immediately afterwards and at three months. Overall, we found no statistically significant increase in SV2A density. However, participants treated in the therapeutic-like setting exhibited more intense mystical-type experiences, longer-lasting psychological benefits, and greater increases in synaptic density than those dosed in the MRI scanner. These findings indicate that psilocybin's neuroplastic effects are modulated by environmental context, with important implications for psychedelic-assisted therapies. ClinicalTrial: NCT03289949.
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 |