Not Yet RecruitingPhase 1

Psilocybin as a Novel Therapy for Residual Anhedonia

United States90 participantsStarted 2026-07

Plain-language summary

The primary objective is to evaluate whether a single dose of psilocybin (25 mg), compared to placebo, can restore fronto-striatal reward circuit function and thereby improve anhedonia and emotional blunting in individuals with residual symptoms despite ongoing SSRI or SNRI treatment. This will be assessed using precision functional mapping (PFM), task-based fMRI, and clinical rating scales (DARS).

Who can participate

Age range

18 Years – 65 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Age between 18 and 65 years * Able to provide voluntary signed and dated informed consent. * Females of childbearing potential (FOCBP) must agree to practice an effective means of birth control throughout the duration of the trial * Males who have FOCBPs as partners must agree to practice an effective means of birth control throughout the duration of the trial * State willingness to comply and be available for all study requirements, including psychological, cognitive, imaging and procedural evaluations for the duration of the study * Meet DSM-5 criteria for major depressive disorder (MDD) * Screening Dimensional Anhedonia Rating Scale (DARS) total score of \< 28.5 points * Have an identified support person * Agree to refrain from taking all non-prescription medications and supplements (nutritional and herbal) for at least 1 week prior to the IP administration session unless approved by the Investigator. Exclusion Criteria: * Inability to speak and understand English sufficiently to complete informed consent and study procedures. * Inability to provide informed consent. * Women who are pregnant or who intend to become pregnant or nurse during the study duration. * Prior exposure to classic psychedelics (i.e., psilocybin, LSD, ayahuasca, and/or mescaline) within the past 1 year. * Current or previous psychiatric conditions that meet DSM-5 criteria for psychotic disorders (i.e., schizophrenia, schizoaffective disorder, MDD with psychosis), bipolar 1 or …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in Dimensional Anhedonia Rating Scale (DARS) Score

Timeframe: Baseline (Week -3), End of Study (Week 8)

Change in Fronto-Striatal Connectivity (pgACC-NAcc FC)

Timeframe: Baseline (Week -3), End of Study (Week 8)

Trial details

NCT IDNCT07607938

SponsorNYU Langone Health

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2030-08-01

Contact for this trial

Joshua Siegel, MD, PhD

646-754-4814 Joshua.Siegel@nyulangone.org

View on ClinicalTrials.gov More Anhedonia trials