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Using Psilocybin to Treat Major Depressive Disorder

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)

Phase 3 Interventional Usona Institute · NCT06308653

This study is testing if a single dose of Psilocybin can help adults with major depression feel better compared to lower doses or a placebo.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment240 (estimated)
Ages18 Years and up
SexAll
SponsorUsona Institute Academic / other
Locations29 sites (Birmingham, Alabama and 28 other locations)
Trial IDNCT06308653 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy, safety, and tolerability of a single oral dose of Psilocybin (25 mg) compared to lower doses and a placebo in adults diagnosed with Major Depressive Disorder (MDD). Approximately 240 participants will be randomly assigned to receive either the active drug or placebo, with their depressive symptoms assessed over a 43-day period following the dose. The study includes a structured psychosocial support framework to enhance the treatment experience, and participants will be monitored for a year to evaluate long-term effects and safety. Outcome measures will focus on changes in depressive symptoms, functional disability, and overall quality of life.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who meet the DSM-5 criteria for Major Depressive Disorder and are currently experiencing a major depressive episode.

Not a fit: Patients who are pregnant, nursing, or have certain cardiovascular or neurological conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients suffering from Major Depressive Disorder.

How similar studies have performed: Other studies have shown promising results with Psilocybin for depression, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Adults ≥18 years old.
* Able to swallow capsules.
* If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
* Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening.
* Have at least moderate severity of depression symptoms at Screening and Trial Baseline.

Exclusion Criteria:

* Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing.
* Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia.
* Have elevated blood pressure.
* Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor.
* Have severe hepatic or renal impairment.
* Have uncontrolled diabetes mellitus or unstable existing thyroid disorder.
* Are hepatitis or HIV positive.
* Have a positive urine drug test for illicit, non-prescribed, or prohibited substances.
* Meet DSM-5-TR criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features ,bipolar disorder (types 1 or 2), antisocial personality disorder, borderline personality disorder or moderate or severe alcohol or drug use disorder
* Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening.
* Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar I disorder.

Where this trial is running

Birmingham, Alabama and 28 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Depressive Disorder, MajorPsilocybinPsychedelicDepressionMajor Depressive DisorderMDDPsychosocialPsychoeducation
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.