Psilocybin Therapy for Depression in Parkinson's Disease (PDP2)

The Efficacy of Psilocybin Therapy for Depression in Parkinson's Disease

The purpose of this study is to understand whether people with Parkinson's Disease and depression have improvement in their symptoms after psilocybin therapy.

Study Overview

• Status: Recruiting
• Conditions: Depression; Parkinson Disease
• Intervention / Treatment: Drug: Psilocybin; Drug: Pimavanserin

Detailed Description

This is a randomized controlled trial of oral psilocybin therapy for depression in people with Parkinson's disease (PD). The primary goal is to examine efficacy of psilocybin therapy in this patient population. We will enroll 60 people ages 40 to 80 with clinically diagnosed early to moderate stage Parkinson's disease (Hoehn and Yahr Stage 1-3 during an "on" period), who meet criteria for moderate or greater depression severity and meet all other inclusion and exclusion criteria at screening. Participants will complete two drug administration sessions where they will each receive a dose of oral psilocybin ranging from low ("microdose") to high in a medically monitored setting with psychotherapeutic support. Participants will also complete a series of psychotherapy sessions before and after each drug administration session. Clinical assessments, neuroimaging, non-invasive brain stimulation, and peripheral blood draws will be used to quantify changes in depression, other non-motor and motor symptoms of PD, quality of life, and selected neural and blood-based biomarkers at multiple time points. Follow-up will continue to 3 months after the second session. Primary endpoints will evaluate efficacy, safety, and tolerability of study procedures.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ellen Bradley, MD
• Study Contact Backup: Name: Brigette Sosa; Phone Number: (415) 935-3489; Email: pdp2@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Joshua Woolley, MD,PhD
      • Sub-Investigator: Ellen Bradley, MD
      • Contact: Kimberly Sakai; Email: pdp2@ucsf.edu
      • Contact: Brigette Sosa; Phone Number: 415-935-3489; Email: pdp2@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 40 to 80
• Comfortable speaking and writing in English
• Have neurologist-diagnosed idiopathic Parkinson's disease (PD), Hoehn and Yahr stages 1 to 3 during an "on" phase (time when medication/DBS for parkinsonian motor feature, including bradykinesia and rigidity is in effect)
• Currently experiencing depressive symptoms
• Able to attend all in-person visits at UCSF as well as virtual visits
• Have a primary care provider, neurologist, or psychiatrist who is actively managing or coordinating

Exclusion Criteria:

• Psychotic symptoms involving loss of insight
• Significant cognitive impairment
• Regular use of medications that may have problematic interactions with psilocybin
• A health condition that makes this study unsafe or unfeasible, determined by study physicians

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin Administration Session 1; Participants will receive one dose of psilocybin ranging from low ("microdose") to high and either pimavanserin or a placebo capsule in a medically monitored setting with preparation sessions before and integration sessions after.	Drug: Psilocybin; Single dose of psilocybin ranging from low ("microdose") to high delivered orally in two separate drug administration sessions with psychological support and monitoring.; Other Names: 4-phosphoryloxy- N,N-dimethyltryptamine; Drug: Pimavanserin; Participants will receive either pimavanserin or placebo during their drug administration sessions.
Experimental: Psilocybin Administration Session 2; Participants will receive one dose of psilocybin ranging from low ("microdose") to high and either pimavanserin or a placebo capsule in a medically monitored setting with preparation sessions before and integration sessions after.	Drug: Psilocybin; Single dose of psilocybin ranging from low ("microdose") to high delivered orally in two separate drug administration sessions with psychological support and monitoring.; Other Names: 4-phosphoryloxy- N,N-dimethyltryptamine; Drug: Pimavanserin; Participants will receive either pimavanserin or placebo during their drug administration sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy of psilocybin for improving depression in people living with Parkinson's disease	Changes in depression as measured by the MADRS	Baseline to 30 days after first drug dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in depression severity	Measured by Beck Depression Inventory-2 (BDI-2) scores	7 days after first drug dose to 90 days after second drug dose
Changes in clinician-assessed depression	Measured by the Montgomery-Asberg Depression Rating Scale (MADRS)	Baseline to 90 days after second drug dose
Changes in anxiety	Measured by the Parkinson Anxiety Scale (PAS)	Baseline to 90 days after second drug dose
Changes in PD symptom severity	Measured by the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Baseline to 90 days after second drug dose
Changes in Quality of Life	Measured by the 36-item Short Form survey (SF-36)	Baseline to 90 days after second drug dose
Changes in cognitive performance	Measured by a multi-task assessment	Baseline to 90 days after second drug dose
Safety and tolerability of psilocybin therapy for depression in people with PD	Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)	Baseline to 90 days after second drug dose
Changes in clinician-rated psychotic symptoms	Measured by the Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS-PD)	Baseline to 90 days after second drug dose
Subjective effects of psilocybin	Measured by the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC)	Up to 30 and 60 days after Baseline
Participant-reported acceptability of study procedures	Measured by the study-specific Treatment Satisfaction Questionnaire-Participant (TSQ-P)	30 days after second drug dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in peripheral inflammatory markers (exploratory)	Measured by blood-based analysis	Baseline to 90 days after second drug dose
Changes in participant reported sleep (exploratory)	Measured by the Parkinson's Disease Sleep Scale-2 (PDSS-2)	Baseline to 90 days after second drug dose
Changes in sleep parameters, physical activity, body temperature, and heart rate (exploratory)	Measured by using passive sensing via a wearable device	Baseline to 30 days after first drug dose
Evaluation of treatment expectations (exploratory)	Measured by the Treatment Expectancy questionnaire consisting of 6 questions from the Stanford Expectations of Treatment Scale. Rating point scale is from 1 (Strongly disagree) to 7 (Strongly agree). Higher scores represent greater expectations of treatment benefit.	Baseline
Evaluation of masking procedures (exploratory)	Measured by the study-specific Masking Questionnaire which includes items to assess perceived treatment assignment. Using a 7-point scale, higher scores represent greater certainty.	Up to 30 and 60 days after Baseline
Changes in brain structure and function (exploratory)	Measured by Positron Emission Tomography (PET) imaging, Magnetic Resonance Imaging (MRI) and Transcranial Magnetic Stimulation (TMS)	Baseline to 30 days after first drug dose

Collaborators and Investigators

• Sponsor: Joshua Woolley, MD, PhD
• Investigators: Principal Investigator: Joshua Woolley, MD,PhD, University of California, San Francisco; Principal Investigator: Ellen Bradley, MD, University of California, San Francisco

Publications and helpful links

Helpful Links

• Click here to take our survey to see if you're eligible

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 30, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Parkinson Disease; Psilocybin; Movement disorder; Psilocybin therapy
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Behavioral Symptoms; Neurodegenerative Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Behavior; Depression; Movement Disorders; Parkinson Disease; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin; pimavanserin
• Other Study ID Numbers: IRB#20-32641

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No