Psilocybin therapy for mood dysfunction in Parkinson's disease: an open-label pilot trial.
Ellen Bradley, Kimberly Sakai, Gisele Fernandes-Osterhold, Balázs Szigeti, Connie Ludwig, Jill L Ostrem, Caroline M Tanner, Meredith A Bock, Katiah Llerena, Patrick R Finley, Aoife O'Donovan, Jose Rafael P Zuzuarregui, Zachary Busby, Amber McKernan, Andrew Penn, Aliss C C Wang, Raymond C Rosen, Joshua Woolley
Neuropsychopharmacology April 9, 2025 DOI: 10.1038/s41386-025-02097-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot Pilot study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | People with mild to moderate stage Parkinson's disease plus depression and/or anxiety |
| Interventions | Psilocybin Psychotherapy |
| Dose | one 10 mg followed by one 25 mg dose |
| Duration | Drug exposure period plus one-month safety assessment for motor and cognitive outcomes; three-month follow-up for mood outcomes |
| Topics | Psilocybin |
| Keywords | Psilocybin therapy Parkinson's disease treatment Psychedelic medicine Neurological research Mental health interventions |
| Citations | 23 |
| Registration | NCT04932434 |
| Key points | Psilocybin therapy was feasible and associated with clinically meaningful improvements in depression, anxiety, and some motor and cognitive symptoms in people with Parkinson's disease, with no serious adverse events. |
Abstract
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot (NCT04932434), we examined the feasibility of psilocybin therapy among people with mild to moderate stage PD plus depression and/or anxiety. 12 participants (mean age 63.2 ± 8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy. There were no serious adverse events, no medical interventions required to manage effects of psilocybin, and no exacerbation of psychosis. Ten participants experienced treatment-emergent adverse events; the most frequent were anxiety, nausea, and increased blood pressure. We observed no worsening of PD symptomology measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). On the contrary, non-motor (MDS-UPDRS Part I: -13.8 ± 1.3, p < 0.001, Hedges' g = 3.0) and motor symptoms (Part II: -7.5 ± 0.9, p < 0.001, g = 1.2; Part III: -4.6 ± 1.3, p = 0.001; g = 0.3) as well as performance in select cognitive domains (Paired Associates Learning [-0.44 ± 0.14, p = .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]) improved post-treatment, and improvements were sustained until the final safety assessment one month following drug exposure. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) scores were 21.0 ± 8.7 and 17.0 ± 3.7, respectively. Both improved to a clinically meaningful degree post-treatment; these improvements persisted to the final assessment three months following drug exposure (MADRS: -9.3 ± 2.7, p = .001, g = 1.0; HAM-A: -3.8 ± 1.7; p = 0.031, g = 0.7). This study provides the first data on psilocybin's effects in any neurodegenerative disease. Results suggest that psilocybin therapy in PD warrants further investigation.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cited by 22
- Emerging mechanisms of psilocybin-induced neuroplasticity TIPS - Trends in Pharmacological Sciences September 16, 2025
- Psychedelic medicine: mechanisms, evidence, and translation to practice BMJ February 23, 2026
- Considerations and cautions for the integration of psilocybin into routine clinical care: a consensus statement from the US National Network of Depression Centers' Task Group on Psychedelics and Related Compounds EClinicalMedicine September 24, 2025
- Psilocybin reduces depressive-like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity- and immune-related genes Research Square November 5, 2025
- Psychedelics for treatment of negative symptoms and depressive symptoms in schizophrenia spectrum disorder: A narrative review Schizophrenia Research March 13, 2026
and 17 more 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 28 more in the library