Psilocybin for Major Depressive Disorder (MDD)
Purpose
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period.
Condition
- Depressive Disorder, Major
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants will be randomized to receive Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo under double-blind conditions. After the initial 6-week Double-blind Period, all participants will proceed into a 1-year Follow-up Period. During this 1-year Follow-up Period, eligible participants who meet pre-determined criteria may be offered open-label Psilocybin 25 mg in the context of a "Set and Setting" (SaS) Protocol.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
- Masking Description
- The following roles will be blinded to the treatment group assignment in the Double-blind Period during the trial: Participant, Investigator, Site Personnel, Facilitators, Efficacy Raters (including Site Raters, Participant Raters, and Central Raters), Contract Research Organization (CRO) Staff, and Sponsor. All roles other than the Sponsor, CRO, and Ethics Committees will also be blinded to the randomization ratio and Patient Health Questionnaire-9 (PHQ-9) score for re-administration eligibility. The Central MADRS Rater will also be blinded to all aspects of the protocol and trial visit for each participant. Blinded trial site personnel will complete administration of the IP. Full blinding of trial personnel, Sponsor, and participants will be maintained until database lock at the conclusion of the trial.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
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Experimental Psilocybin 25 mg |
During the Double-blind Period, participants randomized to receive Psilocybin 25 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
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|
Active Comparator Psilocybin 5 mg |
During the Double-blind Period, participants randomized to receive Psilocybin 5 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
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|
Placebo Comparator Inactive Placebo |
During the Double-blind Period, participants randomized to receive inactive placebo will receive a single dose of Microcrystalline Cellulose (MCC) 25 mg administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
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Other Long-Term Follow-Up |
After the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period. Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met. |
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Recruiting Locations
Birmingham, Alabama 35209
More Details
- Status
- Recruiting
- Sponsor
- Usona Institute
Detailed Description
Double-blind Period: Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators. Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity. Long-term Follow-up Period: After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period. During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.