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DepressionPhase 2PSI-PDNCT07610369

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

A Phase 2 study testing Psilocybin (drug) in people with Depression and Parkinson's Disease (PD), run by Yale University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Depression, Parkinson's Disease (PD)
What is being tested?
Psilocybin (drug)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
10 Jul 2026to Jul 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Currently meeting DSM-5 criteria for another psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin treatment procedures as determined by the investigators.
  • History of meeting DSM-5 criteria for Hallucinogen Persisting Perception Disorder (HPPD).
  • History of using any psychedelic substances including psilocybin, lysergic acid diethylamide (LSD), mescaline (and natural products containing mescaline including peyote and San Pedro cactus), N,N-Dimethyltryptamine (DMT), natural products containing DMT including ayahuasca and 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 2C compounds, 3,4-methylenedioxy-methamphetamine (MDMA), or methylone during the past 6 months at dosages and/or frequencies determined clinically significant by the investigators.
  • Cancer with known central nervous system (CNS) involvement, CNS infection, or other major CNS disease aside from PD.
  • Epilepsy or other seizure disorder in adulthood.
  • Supplemental oxygen requirement.
  • Allergy or intolerance to any of the materials contained in the drug products.
  • Renal insufficiency defined as creatinine clearance < 40 ml/min using Cockraft and Gault equation
  • Insufficiently managed endocrine conditions, including diabetes mellitus and clinically significant thyroid dysfunction.
  • Cardiovascular conditions, including:
  • Elevated blood pressure defined as systolic blood pressure (SBP) >150 or diastolic blood pressure (DBP) >95 taken during Enrollment
  • Tachycardia defined as heart rate (HR) >90 beats per minute taken during Enrollment
  • Bradycardia defined as HR <50 bpm taken during Enrollment
  • Angina
  • History of stroke within the past year
  • Clinically significant ECG abnormality as determined by the investigators, including but not limited to QTc > 450
  • Hepatic dysfunction as indicated by any of the following laboratory values:
  • AST > 3 x upper limit of normal
  • ALT > 3 x upper limit of normal
  • Total bilirubin > 3.0 mg/dl
  • Use of any of the following concomitant medications AND inability/unwillingness to discontinue for at least 5 times the elimination half-life of the agent (specific exceptions are noted) prior to psilocybin administration, including:
  • Agents that may be associated with serotonin syndrome:
  • MAO inhibitors (participants must have discontinued 2 weeks prior to baseline)
  • St. John's Wort
  • S-adenosyl-methionine (SAM-e)
  • 5-Hydroxytryptophan (5-HTP)
  • Dextromethorphan
  • Opioids (e.g., codeine, fentanyl, hydrocodone, meperidine, tramadol)
  • Lithium
  • Linezolid
  • Buspirone
  • Agents that may interact with psilocybin metabolism/effects:
  • Serotonin antagonists (e.g., cyclobenzaprine, ondansetron)
  • Antipsychotics
  • Other dopamine antagonists (e.g., metoclopramide, promethazine, prochlorperazine)
  • Nicotine
  • Modulators of uridine diphosphate (UDP) or glucuronosyltransferase (UGT) (e.g. valproate, diclofenac, mefenamic acid, verapamil, ketoconazole, itraconazole, probenecid, phenobarbital, protease inhibitors)
  • L-methyl folate (>/= 7.5mg/day)
  • Efavirenz
  • Agents that may increase the risk of psychotic symptoms:
  • Stimulants (e.g. modafinil, methylphenidate, atomoxetine, methamphetamine, cocaine, amphetamine derivatives)
  • Anticholinergics (e.g. benztropine, trihexyphenidyl, scopolamine, hyoscyamine)
  • Systemic steroids
  • Tricyclic antidepressants
  • Other medical condition or diagnosis, concomitant medication(s), physical exam finding, laboratory abnormality or health risk identified that precludes participation in study procedures due to safety or feasibility concerns at the discretion of the investigators.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sophie Holmes, PhD contact

203-685-4066

sophie.holmes@yale.edu

Gerard Sanacora, MD contact

gerard.sanacora@yale.edu

United States1 site, 1 recruiting

  • Yale University

    New Haven, Connecticut, 06510

    Sophie Holmes, PhD, 203-685-4066, sophie.holmes@yale.edu

    Sophie Holmes, PhD

    Recruiting

Other trials in United States

About this study

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

Read the 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. Investigators will enroll participants 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 will be used to quantify changes in depression as well as other relevant outcomes (non-motor and motor symptoms of PD, cognitive performance, quality of life). Follow-up will continue to 3 months after the second session. Endpoints will evaluate efficacy, safety, and tolerability of study procedures.

After posting of these trial results, this data will be combined with the data from the trial at UCSF (NCT06455293) for publication purposes.

Being tested
Psilocybin (drug)
Keywords
Parkinson's Diesease, Depression, Psilocybin, Psilocybin therapy, Movement disorder
Medical subject headings
Depression, Parkinson Disease, Movement Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Psilocybin (drug)Drug

    Also called 4-phosphoryloxy- N, N-dimethyltryptamine

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

  • Psilocybin (drug)Drug

    Also called 4-phosphoryloxy- N, N-dimethyltryptamine

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

Study groups in NCT07610369
Study groupRoleWhat they receive
Psilocybin Administration Session 1ExperimentalParticipants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.
Receives: Drug: Psilocybin (drug)
Psilocybin Administration Session 2ExperimentalParticipants will receive one dose of psilocybin ranging from low ("microdose") to high in a monitored setting with preparation sessions before and integration sessions after.
Receives: Drug: Psilocybin (drug)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to 30 days after first drug dose

Secondary outcomes (12)

  1. Adverse Events

    Incidence, severity, and frequency of all Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)

    Measured: Baseline to 90 days after second drug dose

  2. Changes in clinician-rated psychotic symptoms as measured by the Enhanced Scale for the Assessment of Positive Symptoms for Parkinson's Disease (eSAPS-PD)

    The eSAPS-PD is a clinician-administered scale used to track Parkinson's Disease symptom severity. Scores range from 25 to 125, where higher scores indicate more impairment.

    Measured: Baseline to 90 days after second drug dose

  3. Subjective effects of psilocybin as measured by the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC)

    The 5D-ASC is a patient-reported scale used to measure the intensity of an experience during altered states of conciousness. Scores range from 0 to 100, where higher scores indicate more intense psychedelic effects.

    Measured: Up to 30 and 60 days after Baseline

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

    The C-SSRS is a clinician-administered scale used to assess suicide risk. Scores range from 0 to 6, where higher scores indicate more severe suicide risk.

    Measured: Baseline to 90 days after second drug dose

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

    TSQ-P is a patient-reported 7-point scale used to measure patients' satisfaction with their medication. Scores range from 0 to 7, where higher scores indicate greater satisfaction.

    Measured: 30 days after second drug dose

  6. Changes in depression severity as measured by Montgomery-Asberg Depression Rating Scale (MADRS)

    MADRS is a 10-item clinician-administered scale used to measure the severity of depression symptoms. Overall score ranges from 0 to 60, where higher scores indicate more severe depression.

    Measured: Baseline to 90 days after second drug dose

  7. Proportion of participants with a response (defined as a >/=50% decrease in MADRS total score) as measured by the Montgomery-Asberg Depression Rating Scale (MADRS)

    MADRS is a 10-item clinician-administered scale used to measure the severity of depression symptoms. Overall score ranges from 0 to 60, where higher scores indicate more severe depression.

    Measured: 7 days after first drug dose and up to 90 days after second drug dose

  8. Changes in participant reported depression as measured by the Beck Depression Inventory (BDI-II)

    BDI-II is a 21-item patient-reported questionnaire used to assess the severity of depressive symptoms. Total scores range from 0 to 63, with higher scores indicating more severe depression.

    Measured: Baseline up to 90 days after second drug dose

  9. Changes in anxiety as measured by the Parkinson Anxiety Scale (PAS)

    PAS is a 12-item, PD-specific scale used to assess anxiety in adults with Parkinson's disease. Total scores range from 0 to 50 with higher scores indicating more severe anxiety.

    Measured: Baseline to 90 days after second drug dose

  10. Changes in PD symptom severity as measured by the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

    MDS-UPDRS is a 50-item scale used for assessing both motor and non-motor aspects of Parkinson's disease. Total scores range from 0 to 176 with higher scores indicating more severe disease.

    Measured: Baseline to 90 days after second drug dose

  11. Changes in cognitive performance as measured by multi-task assessments to include Probabilistic Reversal Task, Category Switch Task, Simon Task, Delay Discounting Task, California Verbal Learning Test-II, Digit span forward and backward

    Probabilistic Reversal Task measures flexible learning, Category Switch Task measures mental set shifting, Simon Task measures selective attention, Delay Discounting Task measures impulse control/waiting for rewards, California Verbal Learning Test (CVLT-II) measures short- and long-term memory, Digit Span Forward and Backward measures working memory.

    Measured: Baseline to 90 days after second drug dose

  12. Changes in Quality of Life as measured by the 36-item Short Form survey (SF-36)

    SF-36 is a patient-reported 36-item scale used to measure health-related quality of life. Total scores range from 0 to 100 with higher scores indicating better health.

    Measured: Baseline to 90 days after second drug dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2026
  2. Study start10 Jul 2026
  3. Primary completionJul 2030 (estimated)
  4. Study completionJul 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07610369
Sponsor's protocol ID
2000042396
Acronym
PSI-PD
Status last verified
Sep 2026
First submitted
15 May 2026
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Any data, code and software needed for independent verification of research results will be shared freely and publicly per the funder's open access publication policy.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Psilocybin (drug) in people with Depression and Parkinson's Disease (PD), run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 60 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sophie Holmes, PhD (203-685-4066, sophie.holmes@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in depression as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: Baseline to 30 days after first drug dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07610369.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.

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