Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease

Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease: a Pilot Study

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04932434

Acronym

PDP1

Enrollment

Registered

2021-06-21

Start date

2021-08-15

Completion date

2024-12-31

Last updated

2026-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anxiety, Depression, Parkinson Disease

Keywords

Parkinson Disease, Depression, Anxiety, Psilocybin, Psilocybin therapy, Movement disorder

Brief summary

The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy for depression and anxiety in people with Parkinson's disease.

Detailed description

This is an open-label single-arm pilot study of oral psilocybin therapy for depression and anxiety in people with Parkinson's Disease (PD). The primary goal is to examine safety, tolerability, and feasibility of the intervention in this patient population. We will enroll people ages 40 to 75 with clinically diagnosed early stage Parkinson's Disease (Hoehn and Yahr Stage 1-3 during an "off" period), who meet DSM-5 criteria for a depressive or anxious disorder and meet all other inclusion and exclusion criteria at screening. After baseline assessments, participants will complete preparation sessions designed to provide information about the psilocybin experience and to build rapport/trust with the study team. Next, participants will complete a first psilocybin administration session, receiving a low-moderate dose of 10 mg oral psilocybin in a supervised setting with safety monitoring by a physician. Participants who do not experience significant adverse events during or following the session will complete a second psilocybin administration session approximately two weeks later. During the second psilocybin administration session, participants will receive a moderate-high dose of 25 mg oral. The second session will involve the same procedures and level of monitoring as the first. Participants will subsequently complete multiple follow-up sessions designed to assess PD and psychiatric symptoms as well as to provide support as they process their psilocybin experiences. Follow-up will continue to 3 months after the second psilocybin administration session. Primary endpoints will assess safety, tolerability, and feasibility of study procedures. Exploratory efficacy endpoints will assess changes in depressive symptoms, anxious symptoms, and related measures of function.

Interventions

DRUGPsilocybin therapy

* Psilocybin administration session 1: 10mg delivered orally with psychological support and monitoring * Psilocybin administration session 2: 25mg delivered orally with psychological support and monitoring

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Single Group Assignment

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Age 40 to 75 * Comfortable speaking and writing in English * Clinically diagnosed early stage Parkinson's Disease (Hoehn and Yahr Stage 1-3 during an "off" period) who meet DSM-5 criteria for a depressive or anxious disorder and meet all other inclusion and

Exclusion criteria

at screening * Currently experiencing depression and/or anxiety (a formal diagnosis is not necessary) * Able to attend all in-person visits at UCSF as well as virtual visits * Have a care partner/support person available throughout the study * Have an established primary care provider, neurologist, or psychiatrist

Design outcomes

Primary

Measure	Time frame	Description
Movement Disorder Society-sponsored Revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	7 days after first drug dose (which takes place 2-4 weeks after enrollment); 7 and 30 days after second drug dose (which takes place 2 weeks after first drug dose, i.e., 4-6 weeks after enrollment)	This clinician-administered assessment measures the severity of Parkinson's disease symptoms.The MDS-UPDRS has four subscales: * I: Non-motor Experiences of Daily Living -- 13 items * II: Motor Experiences of Daily Living -- 13 items * III: Motor Examination -- 33 items * IV: Motor Complications -- 6 items All 65 items across subscales are rated on a 5-point scale (0-4). Total scores were calculated by summing the scores across all 65 items. Higher scores indicate more severe Parkinson's disease symptoms.
Columbia Suicide Severity Rating Scale (C-SSRS)	7 days after first drug dose (which takes place 2-4 weeks after enrollment); 7 and 30 days after second drug dose (which takes place 2 weeks after first drug dose, i.e., 4-6 weeks after enrollment)	The C-SSRS measures suicidal ideation (SI) in 6 categories, each scored on a binary scale of Yes or No (coded 1 or 0, respectively): 1) Wish to be Dead; 2) Non-specific Active Suicidal Thoughts; 3) Active SI with Any Methods (Not Plan) without Intent to Act; 4) Active SI with Some Intent to Act, without Specific Plan; 5) Active SI with Specific Plan and Intent; 6) Preparatory Acts or Behavior. Total scores are calculated as the sum of the 6 items ratings; the possible range of total scores is from 0 to 6. Higher total scores indicate more severe SI.
Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS-PD)	7 days after first drug dose (which takes place 2-4 weeks after enrollment); 7 and 30 days after second drug dose (which takes place 2 weeks after first drug dose, i.e., 4-6 weeks after enrollment)	The eSAPS-PD measures the severity of positive psychotic symptoms in individuals with Parkinson's disease. Total scores are calculated as the sum of 11 items, each rated on a scale from 0 - 5: Minor Hallucinations, Gustatory Hallucinations, Olfactory Hallucinations, Auditory Hallucinations, Somatic or Tactile Hallucinations, Visual Hallucinations, Persecutory Delusions, Delusions of Jealousy, Delusions of Reference, Capgras Syndrome, and Other Delusions. The range of possible total scores is 0 to 55. Higher total scores indicate more severe psychotic symptoms.
Psychosis and Hallucinations in Parkinson's Disease Questionnaire (PsycH-Q)	On day of first drug dose (which takes place 2-4 weeks after enrollment); On day of, and 11, 18, and 25 days following second drug dose (which takes place 2 weeks after first drug dose, i.e., 4-6 weeks after enrollment)	This self-report questionnaire measures psychotic symptoms in individuals with Parkinson's disease. The questionnaire assesses the frequency and severity of 20 symptom. The frequency of each item is rated from 0 to 4, and the severity of each item is rated from 1 to 4. Scores for each item are determined by multiplying the frequency rating and severity rating. Total scores are then calculated by summing the scores on all 20 items. Possible total scores range from 0 to 320. Higher total scores indicate more severe and more frequent psychotic symptoms.
Neuropsychiatric Inventory Caregiver Distress Questionnaire (NPI-Q)	7 days after first drug dose (which takes place 2-4 weeks after enrollment); 7, 30, and 90 days after second drug dose (which takes place 2 weeks after first drug dose, i.e., 4-6 weeks after enrollment)	This self-report measure is administered to caregivers of participants with Parkinson's disease. Respondents are asked to rate the severity of the symptoms of the individual in their care, as well as the degree of distress this causes them personally (as the caregiver). Twelve symptoms are assessed for both severity and distress, rated on scales from 1 to 3 and 0 to 5, respectively. Total scores on the severity and distress subscales are calculated by summing the respective ratings across the twelve items. Possible total scores range from 12 to 36 on the severity subscale, and from 0 to 60 on the distress subscale.
11-Dimensional Altered States of Consciousness Rating Scale (11D-ASC)	Measured on each drug administration session day, following drug dose	This 94-item, self-report questionnaire measures alterations in perception and cognition following administration of psilocybin. Each item is rated on a scale from 0 to 100. 11 subscales are calculated to measure alterations across different dimensions of perception and cognition, with a composite score consisting of the average score across the 11 subscales. Average composite scores have been reported here.
Incidence of Adverse Events	0-24 hours, 1-7 days, 8-14 days, 15-30 days, and 31-90 days after drug administration	The incidence of Adverse Events are reported here by the amount of, and timing relative to, the study drug dose as a measure of the safety and tolerability of psilocybin therapy for depression and anxiety in individuals with Parkinson's disease.
Retention Rate	90 days following last drug dose	The number of participants completing all stages of the study will be presented as a percentage of the number of total number of participants enrolled in the study.
Treatment Satisfaction Questionnaire (TSQ)	30 days following last drug dose	The Treatment Satisfaction Questionnaire (TSQ) was developed in house to measure participants' overall satisfaction with the study treatment. The measure consists of 5 items rated on a scale from 1 to 7 and three free-response questions (free response items not reported here). Reported are average scores on each of the five items; higher scores represent stronger agreement with the sentiment expressed.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORJoshua Woolley, MD/PhD

University of California, San Francisco

STUDY_DIRECTOREllen Bradley, MD