Magic mushrooms may boost mood and brain health for Parkinson’s disease patients, study reveals

In the first psychedelic study tested on neurodegenerative disease patients, researchers have discovered that psilocybin therapy elicits meaningful improvements in mood, cognition, and motor symptoms — without serious side effects or worsened symptoms.

Psilocybin is a natural compound found in certain psychoactive mushrooms, which have increasingly shown promise in treating depression and anxiety.

The University of California San Francisco (US) researchers initially set out to understand if it could be used to help Parkinson’s patients who often experience debilitating mood dysfunction, next to their motor dysfunction symptoms, and don’t respond well to antidepressants or other medications.

Additionally, clinically significant improvements in mood, cognition, and motor function lasted for weeks after the drug was out of the participant’s systems.

“We are still in very early stages of this work, but this first study went well beyond what we expected,” says the paper’s first author, Ellen Bradley, MD, 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,” she adds. “And they are actually a stronger predictor of patients’ quality of life with Parkinson's than their motor symptoms.”

Lasting mood and motor benefits

While medications like levodopa can relieve symptoms of Parkinson’s disease, there are no approved therapies to slow the progression or reverse the disease itself. The progressive neurodegenerative disorder is characterized by uncontrolled movements due to abnormal brain activity and affects about one million US patients.

Common early physical symptoms include tremors and foot dragging, but Bradley says anxiety and depression in patients with no history of psychiatric problems often precede the onset of motor symptoms by several years.

The researchers say it’s unclear why standard medications often don’t work well for these patients, but mood changes could be part of the neurodegenerative disease process.

To test the safety of psilocybin for these patients, the researchers gave seven men and five women with mild to moderate Parkinson’s disease a 10 mg dose, followed two weeks later by a higher dose of 25 mg.

The patients completed psychotherapy sessions before and after the psilocybin — eight sessions in total — and were evaluated for changes in mood, cognition, and motor functions.

While nearly all participants experienced some adverse events while on the psilocybin, such as anxiety, nausea, and elevated blood pressure, these were not serious enough to require medical intervention.

The participants had “meaningful improvements” in their mood, cognition, and motor symptoms at both their one-week and one-month follow-up appointments. The team evaluated the participants’ mood again three months after their psilocybin sessions and found it was still significantly improved.

The researchers suggested explanations for the improvements. The beneficial impact of psilocybin on the patients’ mood could have led to better cognitive and motor functions. For example, people feel better, which, in turn, helps them socialize and become more active — both key elements of Parkinson’s treatment.

Another theory is that psilocybin could provide relief from multiple symptoms of the disease by reducing inflammation and promoting neuroplasticity — the growth and reconnection of brain cells involved in mood, cognition, and movement regulation.

Expanding into uncharted territory

Following the promising results of this pilot study, the researchers are conducting a larger randomized controlled trial at UCSF, enrolling a larger and more diverse group of patients. The second study incorporates noninvasive brain stimulation, neuroimaging, and other tools to understand how psilocybin impacts inflammation and neuroplasticity.

It will include a second site at Yale University, with the aim of enrolling 100 participants. This work will be funded by the same anonymous donor who paid for the safety pilot as well as by the Michael J. Fox Foundation for Parkinson’s Research.

“The vast majority of brain diseases still lack interventions that change the course of illness,” says the study’s senior author, Joshua Woolley, MD, PhD, 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.”

Researchers in the TrPR Program, within UCSF’s Department of Psychiatry and Behavioral Sciences and the Department of Neurology, teamed up to lead this project, which was funded by an anonymous donor. The findings appeared online earlier this month in Neuropsychopharmacology, a Nature publication.