Phase 2
N=104
A Study of Psilocybin for Major Depressive Disorder (MDD)
Depressive Disorder, Major
Bottom Line
View on ClinicalTrials.gov: NCT03866174 ↗Enrolled (actual)
104
Serious AEs
0.0%
Results posted
Apr 2026
Primary outcome: Primary: Change in Central Rater Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Post-dose Day 43 — -19.1; -6.8 units on a scale — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Psilocybin (Drug); Niacin (Drug); Set and Setting (SaS) Protocol (Other)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- Usona Institute
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Central Rater Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Post-dose Day 43 |
-19.1; -6.8 | <0.001 sig |
| SECONDARY Change in Central Rater MADRS Score From Baseline to Post-dose Day 8 |
-17.8; -5.8 | <0.001 sig |
| SECONDARY Change in On-site Rater Administered Sheehan Disability Scale (SDS) Score From Baseline to Post-dose Day 43 |
-4.07; -1.76 | <0.001 sig |
| SECONDARY Sustained Depressive Symptom Response Defined as a ≥ 50% Reduction From Baseline Central Rater MADRS Score at All Post-dose Assessments |
20; 5; 28; 39 | 0.002 sig |
| SECONDARY Sustained Depressive Symptom Remission Defined as a Central Rater Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score ≤ 10 at All Post-dose Assessments |
12; 4; 36; 40 | 0.051 |
Summary
One hundred participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.
The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo in otherwise medically-healthy participants, assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.
Eligibility Criteria
Inclusion Criteria
- 21 to 65 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
- Have an identified support person and agree to be accompanied home by that person following dosing
- Have sustained moderate-severe depression symptoms at Screening and Baseline
- Meet DSM-5 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
Exclusion Criteria
- Women who are pregnant or who intend to become pregnant during the study or who are currently nursing
- Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition
- Have a history of stroke or Transient Ischemic Attack (TIA)
- Have moderate to severe hepatic impairment
- Have epilepsy
- Have insulin-dependent diabetes
- Have a positive urine drug test
- Nicotine dependence that would disallow an individual to be nicotine free for the 7-10 hours during the dosing period
- Meet DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or Bipolar I or Bipolar II Disorder
- Meet DSM-5 criteria for antisocial personality disorder
- Meet DSM-5 criteria for a moderate or severe alcohol or drug use disorder
Data sourced from ClinicalTrials.gov (NCT03866174). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.