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

NCT07610369 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000042396
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Depression; Parkinson's Disease (PD)

Keywords

Parkinson's Diesease; Depression; Psilocybin; Psilocybin therapy; Movement disorder

Outcome Measures

Primary Outcomes (1)

• Change in depression as measured by the Montgomery-Asberg Depression Rating Scale (MADRS)

  MADRS is a 10-item clinician-administered scale used to measure the severity of depressive symptoms. Total scores range from 0 to 60 with higher scores indicating more severe depression.

  Baseline to 30 days after first drug dose

Secondary Outcomes (12)

• Adverse Events

  Baseline to 90 days after second drug dose

• Changes in clinician-rated psychotic symptoms as 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 as measured by the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC)

  Up to 30 and 60 days after Baseline

• Suicidality as measured using the Columbia Suicide Severity Rating Scale (C-SSRS)

  Baseline to 90 days after second drug dose

• Participant -reported acceptability of study procedures as measured by the study-specific Treatment Satisfaction Questionnaire-Participant (TSQ-P)

  30 days after second drug dose

Other Outcomes (7)

• Changes in sleep parameters as measured using passive sensing via an Oura ring (exploratory)

  Baseline to 30 days after the second drug dose

• Changes in physical activity as measured using passive sensing via an Oura ring (exploratory)

  Baseline to 30 days after the second drug dose

• Changes in body temperature as measured using passive sensing via an Oura ring (exploratory)

  Baseline to 30 days after the second drug dose

Study Arms (2)

Psilocybin Administration Session 1

EXPERIMENTAL

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Drug: Psilocybin (drug)

Psilocybin Administration Session 2

EXPERIMENTAL

Participants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.

Drug: Psilocybin (drug)

Interventions

Psilocybin (drug) DRUG

Single dose of psilocybin ranging from low ("microdose") to high delivered orally with psychological support and monitoring

Also known as: 4-phosphoryloxy- N, N-dimethyltryptamine

Psilocybin Administration Session 1

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and provide informed consent
• 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)
• Have no changes in medication or major surgical procedures anticipated for treatment duration
• Have a score \>/=20 on the Beck Depression Inventory-2 (BDI-2), consistent with moderate or greater depressive symptom severity, at Baseline.
• For people who can become pregnant: agree to use highly effective contraception from entry into the trial through Day B30 assessments (4 weeks after the second psilocybin administration session) and agree to not breastfeed. Acceptable methods of contraception are: An intrauterine device (IUD), hormone-based contraceptives (birth control pills) , condoms (internal or external) must be used with another method (other than spermicide), and complete abstinence from sexual activity that could result in pregnancy.
• Agree that for one week preceding each psilocybin session, they will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the research team. Exceptions will be evaluated by the research team and assessed for safety. Agree to abstain from all tobacco and nicotine use for the duration of the study.
• Agree to consume approximately the same amount of caffeine-containing beverages that they usually consume before arriving at the research unit on the mornings of psilocybin administration sessions.
• Agree to avoid sedative-hypnotic medications (e.g., benzodiazepines, zolpidem, zopiclone, zaleplon) taken on an as-needed basis for a minimum of 5 half-lives prior to each psilocybin administration session and for 24 hours after each psilocybin administration session.
• Agree to avoid opioid medications taken on an as-needed basis for a minimum of 5 half-lives prior to each psilocybin administration session and for 24 hours after each psilocybin administration session.
• Agree not to use products or substances containing Δ9-tetrahydrocannabinol (THC) and/or cannabidiol for at least 7 days prior to each psilocybin administration session and for 24 hours after each psilocybin administration session.
• Agree to not use non-prescribed narcotics (eg. heroine, fentanyl), depressants (eg. Barbiturates, benzodiazepines) and/or inhalants for the duration of participation in the trial.
• Agree not to consume alcoholic beverages for at least 24 hours prior to and 24 hours following each psilocybin administration session.
• Have a primary care provider, neurologist, or psychiatrist who is actively managing or coordinating care and is available for consultation with the study medical monitor.

You may not qualify if:

• Any indication of forms of parkinsonism other than idiopathic Parkinson's disease.
• Cognitive impairment, defined as a Montreal Cognitive Assessment (MoCA) score \<24.
• Symptomatic orthostatic hypotension.
• Currently receiving electroconvulsive therapy (ECT) or treatment via transcranial magnetic stimulation (TMS). Previous treatment with ECT and/or TMS is permitted; last treatment must be at least 30 days prior to entry into this trial.
• Treatment in a clinical trial within 30 days of entry into this trial or treatment with another investigational drug or other intervention within 30 days or 5 half-lives, whichever is longer, prior to entry into this trial.
• Pregnancy as indicated by a positive urine pregnancy test during screening, lactation, or the intention of becoming pregnant within 3 months of entry into this trial.
• Current severity of psychiatric symptoms warranting immediate treatment as determined by the study medical staff (e.g. due to inability to provide for basic needs/safety). The study medical staff will assess these individuals, determine the appropriate level of care, and coordinate with the individual's primary providers to ensure close follow-up.
• High risk of self-harm/suicide, as determined by the Columbia-Suicide Severity Rating Scale (C-SSRS) risk screen, specifically: participant answers "yes" to item 4 or 5 suggesting intent to act on suicidal thoughts OR participant has made a serious suicide attempt within the 12 months prior to entry into this trial.
• History of meeting DSM-5 criteria for a schizophrenia spectrum disorder, other psychotic disorder, or a mood disorder with psychotic features.
• History of delusional symptoms or any other psychotic symptoms accompanied by a loss of insight. Exceptions may be made at the investigators' discretion in cases of a history of psychotic symptoms that were attributable to substance or medication use.
• Current delusional symptoms or any other psychotic symptoms accompanied by a loss of insight.
• History of a schizophrenia spectrum disorder in a first-degree relative.
• History of bipolar disorder 1 in a first-degree relative, in whom illness onset was prior to age 40.
• Current or history of meeting DSM-5 criteria for a bipolar disorder.
• Current or history within the last 2 years of meeting DSM-5 criteria for a moderate or severe alcohol or drug use disorder, excluding caffeine.

Sponsors & Collaborators

• Yale University: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Depression; Parkinson Disease; Movement Disorders

Interventions

Psilocybin; Pharmaceutical Preparations; N,N-Dimethyltryptamine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals

Study Officials

• Sophie Holmes, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sophie Holmes, PhD

CONTACT

203-685-4066; sophie.holmes@yale.edu

Gerard Sanacora, MD

CONTACT

gerard.sanacora@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This trial is testing various doses of psilocybin. Participants, study staff and clinical assessors will be blinded to individual treatment conditions until study close-out. The clinician administered instruments will be administered by different clinical study staff than the facilitators who provide the preparation, psilocybin therapy, and integration sessions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry and Neurology

Model Details: All participants will receive two doses of psilocybin ranging from low ("microdose") to high. All participants will receive three psilocybin preparation sessions, two administration sessions of a single dose of psilocybin within a therapeutic environment (6-8 hours), five integration sessions, and two follow up visits. All drugs will be orally administered during the dosing sessions. The study procedures will follow best practices for administering psilocybin in clinical trials.

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: May 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The IPD will be shared at the end of the research project and for 1 year after that.
• Access Criteria: The public will be able to access the IPD and supporting information, the IPD accessed will be data and code generated from the project and they will be able to access it from a community-recognized repository.

Locations

US (1)