Psilocybin shows promise for improving mood, cognition, and motor symptoms in Parkinson’s disease

A small pilot study has found that psilocybin, the active compound in psychedelic mushrooms, may improve not only mood but also cognitive and motor symptoms in individuals with Parkinson’s disease. The results surprised the research team, who initially aimed only to evaluate the drug’s safety. Instead, participants experienced noticeable improvements that lasted for weeks following a single high-dose session. The findings, published in Neuropsychopharmacology, mark the first time a psychedelic has been tested in people with any neurodegenerative disease.

Parkinson’s disease is best known for its motor symptoms, including tremor, stiffness, and slowed movement. But many people with the disease also struggle with depression and anxiety, which often begin years before motor symptoms appear. These mood issues are not just emotionally distressing—they are strongly linked to faster physical decline and worse overall quality of life. Standard treatments for depression and anxiety, such as antidepressants, are often less effective in people with Parkinson’s, making the search for new therapeutic options especially urgent.

Psilocybin is a naturally occurring psychedelic compound that is converted in the body into psilocin, which interacts with serotonin receptors in the brain. Studies in major depression and anxiety linked to terminal illness have shown that even a single dose of psilocybin, when paired with psychotherapy, can lead to rapid and long-lasting improvements in mood. Scientists believe the drug may help the brain form new neural connections, a property referred to as neuroplasticity. These effects may be particularly relevant for people with Parkinson’s disease, who exhibit disrupted serotonin signaling, inflammation, and loss of neural connectivity—all factors that may contribute to both mood and motor symptoms.

Given the complex neurobiology of Parkinson’s and concerns about possible drug interactions and psychosis risk, the research team at the University of California, San Francisco set out to test the safety and tolerability of psilocybin in this population. They enrolled 12 participants between the ages of 40 and 75, all of whom had mild to moderate Parkinson’s disease and met diagnostic criteria for depression or anxiety. People with significant cognitive impairment, active psychosis, or other medical risks were excluded from the trial. Most participants were already being treated with levodopa, the most common medication for managing motor symptoms of Parkinson’s.

Each participant underwent two supervised psilocybin sessions on a research unit at UCSF. The first dose was a lower, safety-focused 10 milligram dose, followed about two weeks later by a higher, 25 milligram therapeutic dose. Both sessions were paired with multiple psychotherapy visits before and after. The therapists provided preparation, emotional support during the experience, and integration afterward.

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To track the effects of psilocybin, the researchers used a range of assessments. These included standard clinical rating scales for motor and non-motor Parkinson’s symptoms, mood and anxiety measures, cognitive performance tasks, and caregiver observations. Safety was monitored throughout the sessions, including blood pressure, heart rate, and reports of any adverse psychological or physical effects.

The study found that psilocybin was generally well tolerated. The most common side effects during the sessions included mild anxiety, nausea, and temporary increases in heart rate or blood pressure. Two participants reported intense anxiety during one of the sessions, and one of them experienced a transient worsening of tremor and increased thoughts about death related to future disability. However, no serious adverse events occurred, and suicidal ideation decreased overall after treatment.

Beyond safety, the researchers observed a range of improvements across different symptom domains. Participants reported significant reductions in depression and anxiety one week after the high-dose session, and these gains were maintained at the three-month follow-up. Motor symptoms also improved, as measured by both self-reports and clinician ratings. These included reductions in everyday motor difficulties and improvements in motor exam scores. The magnitude of these improvements exceeded thresholds considered clinically meaningful.

Cognitive function also improved in several domains. Participants performed better on tests of memory, spatial working memory, and cognitive flexibility. These gains were still present a month after the psilocybin session. Interestingly, caregiver reports also reflected meaningful changes. Family members noted that participants were less distressed by neuropsychiatric symptoms and showed fewer behavioral issues. They also expressed high satisfaction with the treatment.

While the improvements in mood were expected based on prior research in depression, the benefits in motor symptoms and cognition were unexpected. The authors suggest several possible explanations. One is that psilocybin may directly influence dopamine and serotonin signaling in ways that support motor control. Another is that improving mood may indirectly benefit motor function, as depression is associated with increased stress and biological changes that can worsen physical symptoms. A third possibility is that psilocybin may influence the underlying disease process through its effects on inflammation, neural plasticity, or other brain systems disrupted in Parkinson’s.

“We are still in very early stages of this work, but this first study went well beyond what we expected,” said the paper’s first author, Ellen Bradley, an assistant professor and associate director of UCSF’s Translational Psychedelic Research Program (TrPR). “Many people don’t realize this, but mood symptoms in Parkinson’s are linked to a faster physical decline. And they are actually a stronger predictor of patients’ quality of life with Parkinson’s than their motor symptoms.”

But the study has important limitations. With only 12 participants and no placebo group, the findings must be interpreted with caution. Expectancy effects and the powerful psychological context of the therapy sessions may have contributed to the observed improvements. Also, because the study excluded people with more advanced disease or significant medical complications, it’s unclear how generalizable the results are. Future research will need to include more diverse and larger samples to better understand the risks and benefits.

Encouraged by the results of this pilot study, the researchers have launched a larger randomized controlled trial involving 100 participants across two sites: UCSF and Yale University. This follow-up study will include brain imaging, noninvasive brain stimulation, and blood tests to help identify how psilocybin affects the brain and immune system. The hope is to uncover biological mechanisms behind the clinical improvements and determine whether psilocybin could one day become part of Parkinson’s care.

“The vast majority of brain diseases still lack interventions that change the course of illness,” said the study’s senior author, Joshua Woolley, an associate professor at UCSF and director of the TrPR Program. “We can often treat the symptoms, but we don’t alter the trajectory or prevent decline. Now, that’s beginning to change. These results raise the exciting possibility that psilocybin may help the brain repair itself.”

The study, “Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial,” was authored by 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, and Joshua D. Woolley.