In the first clinical trial of psilocybin in a neurodegenerative disorder, researchers found that the treatment could be effective at managing depression and anxiety in patients with Parkinson’s disease. The open-label pilot study found significant improvements in mood symptoms that persisted for 3 months following treatment.
The researchers enrolled 12 participants with mild to moderate Parkinson’s disease (PD) (mean age = 63.2 years) who also met criteria for depressive and/or anxiety disorders. The participants received two oral doses of psilocybin—a 10-mg safety dose followed by a 25-mg treatment dose approximately 2 weeks later—administered in conjunction with psychotherapy, according to lead study author Ellen R. Bradley, MD, of the University of California, San Francisco, and her colleagues.
The results suggested that psilocybin therapy not only improved mood symptoms but may have also benefited motor and nonmotor symptoms of PD.
Concerns regarding the safety of psilocybin in this population—including the risk of exacerbated psychosis or autonomic instability—didn't materialize. There were no increases in psychotic symptoms, and none of the participants required pharmacologic intervention during psilocybin administration.
The researchers reported no serious adverse events. Ten participants experienced treatment-emergent adverse events, most commonly anxiety, nausea, and increased blood pressure. No medical interventions were required during psilocybin sessions, and no worsening of PD symptoms was observed, as assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).
Improvements in Multiple Clinical Domains
Nonmotor symptoms improved significantly following treatment (MDS-UPDRS Part I: –13.8), as did motor symptoms (Part II: –7.5) and motor exam scores (Part III: –4.6). These improvements were maintained through the 1-month posttreatment assessment.
Cognitive performance also improved in several areas. Significant posttreatment gains were observed in visual learning (Paired Associates Learning), spatial working memory, and cognitive flexibility (Probabilistic Reversal Learning). Depression scores on the Montgomery–Åsberg Depression Rating Scale improved by a mean of –9.3 from a baseline score of 21 at the 3-month follow-up. Anxiety scores on the Hamilton Anxiety Rating Scale also improved (mean change = –3.8 vs 17).
Mechanistic Considerations and Participant Experience
The researchers proposed several potential mechanisms by which psilocybin might benefit patients with PD, including modulation of serotonergic signaling, anti-inflammatory activity, and promotion of neuroplasticity—processes potentially relevant to both mood and motor dysfunction in PD.
All 12 participants agreed to some extent that the treatment plus psychotherpy session were helpful and would recommend it to others. Ten participants reported that the treatment experience was challenging to some degree.
The study’s limitations included its small sample size, open-label design, and lack of racial diversity. Most participants were White, and all had mild to moderate PD. The researchers noted the need for randomized controlled trials to confirm the safety and efficacy of psilocybin therapy in this population.
“Results of this initial pilot study suggest that psilocybin therapy may have promise as a new treatment for mood dysfunction in PD, but rigorous efficacy testing is a crucial next step.,” said Dr. Bradley and her colleagues. "Further, this study treated psilocybin therapy as a combined intervention (psilocybin plus psychotherapy sessions) and thus the relative contributions of the drug vs psychotherapy cannot be determined," they added.
Disclosures can be found in the study.
Source: Neuropsychopharmacology