SAN FRANCISCO — Could a naturally occurring psychedelic compound be the remedy for mood dysfunction, which is highly prevalent in Parkinson’s disease (PD)?
That was the question addressed in a recent study, which noted that mood dysfunction is a major predictor of functional decline, and that difficult to treat-novel interventions are critically needed.
Researchers from the University of California San Francisco and the San Francisco VA Healthcare System suggested that psilocybin shows early promise for treating depression and anxiety. Its potential in PD is unknown, however, because safety concerns have excluded patients with neurodegenerative disease from previous trials.
In the open-label pilot, the study team examined the feasibility of psilocybin therapy among patients with mild- to moderate-stage PD plus depression and/or anxiety. In the pilot study, 12 participants (mean age 63.2 ±8.2 years, 5 women) received psilocybin (one 10 mg followed by one 25 mg dose) with psychotherapy.
No serious adverse events were identified, no medical interventions were required to manage the effects of psilocybin, and no exacerbation of psychosis occurred, they wrote in Neuropsychopharmacology.1
The authors reported that 10 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),” they wrote. “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.”
They added that the 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, noting, “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 = 0.001, g = 1.0; HAM-A: -3.8 ± 1.7; p = 0.031, g = 0.7).”
The researchers concluded, “This study provides the first data on psilocybin’s effects in any neurodegenerative disease. Results suggest that psilocybin therapy in PD warrants further investigation.”
- Bradley ER, Sakai K, Fernandes-Osterhold G, Szigeti B, et. AlPsilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial. Neuropsychopharmacology. 2025 Apr 9. doi: 10.1038/s41386-025-02097-0. Epub ahead of print. PMID: 40205013.
