Psilocybin improves mood, motor symptoms in patients with Parkinson’s disease

Key takeaways:

• Treatment with psilocybin led to improvement in motor, non-motor and psychiatric symptoms for up to 1 month.
• Results suggest that psilocybin therapy in PD warrants further investigation, researchers wrote.

Treatment with psilocybin was linked to improvements in motor and non-motor symptoms of Parkinson’s disease, as well as associated psychiatric conditions, with sustained results up to 1 month, results of a pilot study show.

“Basic science discoveries have generated a lot of enthusiasm about the potential of psychedelics for Parkinson’s,” Ellen Bradley, MD, assistant professor, department of psychiatry and behavioral sciences, Weill Institute for Neurosciences at the University of California, San Francisco, told Healio.

“We’ve lacked even initial safety data in humans with PD, or any other neurodegenerative disorder. That’s the major gap we wanted to fill in this first phase of work,” Bradley said.

Although psychiatric issues such as anxiety and depression often accompany a diagnosis of PD and presage functional decline, effective treatments are few, Bradley and colleagues wrote. Psilocybin has demonstrated some success in treatment of anxiety and depression, but its potential in PD is still unknown.

The open-label pilot study examined the safety, efficacy and tolerability of psilocybin in 12 individuals (mean age 63.2 ± 8.2 years; 58.3% men) diagnosed with mild to moderate PD plus anxiety and/or depression. Three initial enrollees were not treated with dopaminergic drugs for PD-related motor symptoms, with nine patients prescribed a stable carbidopa-levodopa regimen.

All participants received two doses of synthetic psilocybin: a single 10 mg dose followed by one 25 mg dose 2 weeks later, provided the first dose was well-tolerated. Eight sessions of one-to-one psychotherapy interspersed before, during and after dosing accompanied the treatments.

Vitals were assessed at baseline, then at irregular intervals up to 420 minutes after each psilocybin dose, under medical supervision.

Subjective drug experience was measured by the 5-Dimensional Altered States of Consciousness (5D-ASC) scale. Safety and tolerability with respect to PD symptoms were measured at 1 week after the 10 mg dose and 1 week and 1 one month following the 25 mg dose using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).

Anxiety was tracked with the Hamilton Anxiety Rating Scale (HAM-A) and depression by the Montgomery-Asberg Depression Rating Scale (MADRS).

According to results, patients did not report any serious adverse events or medical interventions that required dosing adjustments. No symptoms of psychosis were worsened. Treatment-emergent adverse events occurred in 10 participants, with the most frequent being anxiety, nausea and increased blood pressure.

Ellen Bradley

The researchers additionally reported that participants’ subjective experience trended higher after the 25 mg dose compared with the 10 mg dose, but not significantly so. Analysis of 5D-ASC scores from the pilot study compared with a previous trial of 25 mg psilocybin therapy for major depressive disorder indicated higher subjective intensity for those enrolled in the pilot study.

Bradley and colleagues also reported significant improvement in both motor symptoms (MDS-UPDRS Part II) and non-motor symptoms (MDS-UPDRS Part I) at the 1-month follow up, -7.5 points and -13.75 points, respectively.

Data further showed anxiety (HAM-A) and depression (MADRS) were improved at 1 week post treatment, with depression significantly lessened at 1 month whereas anxiety was not; improvements for both conditions, however, were sustained up to 3 months after dosing. Mean change from baseline to 90-day follow up were -3.83 points and -9.33 points, respectively.

Results from the pilot, Bradley and colleagues wrote, suggest that psilocybin therapy in PD warrants further investigation. A randomized controlled trial, based at UCSF, is scheduled to expand to a second site at Yale University, with a goal of enrolling 100 participants, according to a release related to the study.

“These findings are exciting, but we can’t draw conclusions from a small pilot. We’re now on to the next phase, conducting a much larger trial designed to test efficacy and figure out psilocybin’s mechanisms of action in PD,” Bradley told Healio. “The goal is to get more targeted, effective treatment options in patients’ hands as quickly as possible.

Reference:

How ‘magic mushrooms’ could help Parkinson’s disease patients. https://www.eurekalert.org/news-releases/1082246. Published April 29, 2025. Accessed May 2, 2025.

For more information:

Ellen Bradley, MD, can be reached at ellen.bradley@ucsf.edu and on LinkedIn here.