Psilocybin Therapy for Parkinson's Disease
Article Title: “Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial”
Author: Ellen R. 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 D. Penn, Aliss C. C. Wang, Raymond C. Rosen, Joshua D. Woolley
Publication Date: March 2025
Background
Parkinson’s disease is widely known for its tremors and movement difficulties, but those living with the condition know all too well that the challenges go far beyond motor control. Depression and anxiety are incredibly common among people with Parkinson’s, often leading to a faster decline in overall functioning and quality of life. Unfortunately, treatments for these mood-related symptoms are notoriously limited and often ineffective.
Over the past decade, psilocybin—the psychoactive compound found in certain mushrooms—has been making headlines for its potential to treat mood disorders like depression and anxiety. But until now, people with neurodegenerative diseases like Parkinson’s have been left out of these studies, largely due to safety concerns. That’s what makes this new pilot trial from researchers at UCSF so exciting—it’s the first of its kind to explore whether psilocybin therapy could be safe and helpful for people with Parkinson’s who are also dealing with mood dysfunction.
Study Overview
This was a small but significant open-label pilot trial involving 12 adults with mild to moderate Parkinson’s disease, all of whom also had a diagnosis of either depression or anxiety. Each participant underwent a course of psilocybin-assisted therapy, which included two psychedelic sessions—first a 10mg “safety dose,” followed two weeks later by a more therapeutically targeted 25mg dose. Alongside the medicine, participants received extensive psychotherapy before, between, and after their dosing sessions to ensure emotional support and integration.
The study’s main aim was to evaluate safety: would the participants tolerate the treatment well, particularly given the known risks around cardiovascular stress and the possibility of psychosis in this population? But the researchers were also eager to get a sense of whether psilocybin might improve mood and other symptoms in a way that was meaningful and measurable.
Key Findings
What they discovered was nothing short of compelling. Not only was the therapy well tolerated—there were no serious adverse events—but participants showed marked and lasting improvements in multiple areas of their health.
Yes, some people did experience temporary side effects like nausea, anxiety, or a rise in blood pressure, especially during the sessions themselves. But these effects were expected and managed safely. More importantly, participants did not experience any worsening of Parkinson’s symptoms or psychotic episodes, which had been a major concern going into the study.
In fact, the researchers found improvements across several domains:
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Depression and anxiety scores dropped significantly and remained lower even three months after the final dose.
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Motor symptoms actually improved—a surprising and encouraging outcome, given that the treatment wasn’t intended to directly target movement.
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Cognitive performance, especially in areas like memory and flexibility, also saw gains.
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Care partners, who were closely observing participants, reported noticeable reductions in neuropsychiatric symptoms such as distress and emotional volatility.
All in all, the treatment seemed to leave participants feeling and functioning better than before—both mentally and physically.
Discussion
While this was a small, non-randomised trial, it carries significant weight simply because it shows that psilocybin can be administered safely to people with Parkinson’s in a clinical setting. That alone is groundbreaking.
Even more remarkable is the ripple effect of benefits that were observed. The improvements in mood were expected, but the gains in motor function and cognition open up fascinating questions. Could the relief of depression lead to better motor outcomes indirectly? Or is psilocybin doing something deeper—perhaps promoting plasticity and neuroregeneration in a way that directly helps the nervous system function more smoothly?
Researchers don’t have clear answers yet, but the study suggests that psilocybin’s effects might reach beyond mood, potentially touching the underlying biology of Parkinson’s itself.
Still, it’s important to approach these results with a healthy dose of caution. The sample size was small, and the study did not include a control group. Placebo effects—especially in Parkinson’s—are well known and powerful. Future studies will need to replicate these results in larger, more rigorous trials.
Implications
For those in the Parkinson’s community—patients, care partners, and clinicians alike—this study offers a glimmer of hope. It suggests that psychedelic therapy might be a viable path forward for addressing the emotional and cognitive toll of the disease. It also opens the door to the broader use of psychedelics in neurodegenerative medicine, where treatment innovation is desperately needed.
Potential Application
If future trials confirm what this pilot study has found, psilocybin therapy could become a valuable new tool for Parkinson’s care. Not only might it help ease the burden of depression and anxiety, but it could also improve daily functioning, emotional resilience, and even mobility. As psychedelic-assisted therapy continues to gain legitimacy, protocols tailored for people with chronic and complex illnesses like PD will be an important area of development.
Conclusions
This early but carefully conducted study suggests that psilocybin therapy, delivered in a supportive psychotherapeutic framework, may offer much-needed relief for people with Parkinson’s disease who are grappling with depression and anxiety. Its potential benefits on mood, motor symptoms, and cognitive flexibility are striking—and pave the way for more expansive and controlled studies in the near future.
Reference:
Bradley, E. R., Sakai, K., Fernandes-Osterhold, G., Szigeti, B., Ludwig, C., Ostrem, J. L., Tanner, C. M., Bock, M. A., Llerena, K., Finley, P. R., O’Donovan, A., Zuzuarregui, J. R. P., Busby, Z., McKernan, A., Penn, A. D., Wang, A. C. C., Rosen, R. C., & Woolley, J. D. (2025). Psilocybin therapy for mood dysfunction in Parkinson’s disease: An open-label pilot trial. Neuropsychopharmacology. https://doi.org/10.1038/s41386-025-02097-0
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