Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.
Level 4 - case-series / case-control
Uncontrolled open-label clinical pilot trial (case series design)
PubMed 40205013 · doi:10.1038/s41386-025-02097-0
What was done
In an open-label pilot trial (NCT04932434), researchers evaluated the feasibility, safety, and preliminary efficacy of psilocybin-assisted psychotherapy in 12 participants with mild-to-moderate Parkinson's disease (PD) and comorbid depression and/or anxiety (mean age 63.2 ± 8.2 years; 5 women). Participants received two oral psilocybin doses (one 10 mg followed by one 25 mg dose) combined with psychotherapy. Safety outcomes, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), cognitive tests, Montgomery-Asberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HAM-A) were assessed at baseline and post-treatment out to three months.
What was found
There were no serious adverse events, medical interventions, or worsening of psychosis or PD symptoms. Ten participants reported treatment-emergent adverse events (most commonly anxiety, nausea, and increased blood pressure). At one month post-treatment, improvements occurred in MDS-UPDRS Part I (-13.8 ± 1.3, p < 0.001, Hedges' g = 3.0), Part II (-7.5 ± 0.9, p < 0.001, g = 1.2), and Part III (-4.6 ± 1.3, p = 0.001, g = 0.3), as well as cognitive tasks: Paired Associates Learning (-0.44 ± 0.14, p = 0.003, g = 0.4), Spatial Working Memory (-0.52 ± 0.17, p = 0.003, g = 0.7), and Probabilistic Reversal Learning (2.9 ± 0.9, p = 0.003, g = 1.3). From baseline MADRS (21.0 ± 8.7) and HAM-A (17.0 ± 3.7), improvements persisted at three months for MADRS (-9.3 ± 2.7, p = 0.001, g = 1.0) and HAM-A (-3.8 ± 1.7, p = 0.031, g = 0.7).
Why it matters
This study provides the first preliminary clinical safety and efficacy data for psilocybin in a neurodegenerative disease, suggesting psilocybin therapy is feasible and warrants controlled evaluation in Parkinson's disease.
Limits
The study is limited by a very small sample size (n = 12) and an open-label, single-arm design with no control or placebo group, introducing high risk of expectancy effects and observer bias. The relative therapeutic contributions of psilocybin versus psychotherapy cannot be distinguished, and follow-up was limited to three months.
Cited by
- supports An open-label trial at UCSF by Ellen Bradley and Josh Woolley found improvements in motor symptoms from psilocybin in Parkinson's disease patients.