Psilocybin as a New But Simple Test for Residual Anhedonia in Depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 1 trial will give a one-time 25 mg psilocybin dose or placebo to adults with major depressive disorder who still experience anhedonia and emotional blunting while on an SSRI/SNRI. Researchers will assess brain reward circuits using fMRI and collect clinical questionnaires, including the Dimensional Anhedonia Rating Scale. The study compares psilocybin to placebo to see if it can improve symptoms and brain function related to reward. Safety and tolerability will be monitored throughout the study.

Why it matters

Who can join: the full rules

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 2 disorder, or current diagnosis of active substance use disorder.
* Have active suicidal ideation with intent, based on Columbia-Suicide Severity Rating Scale (C-SSRS assessment (severity score \> 3) at the Screening visit, confirmed by the Investigator.
* Have made a medically significant suicide attempt (i.e., one that had a significant possibility of causing death or permanent harm in the absence of intervention) within the past 12 months, based on Screening C-SSRS assessment and confirmation by the Investigator.
* Immediate family history (i.e., parents, full siblings, or half siblings) with known or suspected psychotic disorder.
* Presence of medical conditions that may confound results of imaging study or that are contraindications to or psilocybin exposure (i.e., neurological, renal, hypertension, metabolic or cardiovascular disease or pregnancy);
* Presence of contraindications to MRI scanning (implantable devices, bone hardware, various IUD).
* Participants who received electroconvulsive therapy (ECT), trans magnetic cranial stimulation (TMS), and/or ketamine in the past 90 days.
* Has any other physical or psychological symptom, medication, or other relevant finding prior to randomization that, based on the clinical judgment of trial personnel, would make a participant unsuitable for the trial.
* Are unable or unwilling to discontinue taking any protocol-prohibited medications and supplements.

Where it's running

• NYU Langone Health
  New York, New York, United States Recruiting

Study contacts

• Principal investigator: Joshua Siegel, MD, PhD — NYU Langone Health
• Study coordinator: Julia Diamond
• Email: Julia.Diamond@nyulangone.org
• Phone: 646-754-4744

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.