Psilocybin for Major Depressive Disorder (MDD) (uAspire)
This Phase III, randomised, triple-blind, multicentre trial (n=240) compares single oral psilocybin 25 mg, psilocybin 5 mg, and inactive placebo in adults with Major Depressive Disorder using a Set and Setting psychosocial support protocol.
Detailed Description
Randomised, parallel-group Phase III trial enrolling approximately 240 adults meeting DSM-5-TR criteria for major depressive disorder; participants are assigned to psilocybin 25 mg, psilocybin 5 mg, or inactive placebo under triple-blind conditions for a single dosing session.
Investigational product is given as a single oral HPMC capsule with a Set and Setting (SaS) protocol: preparatory meetings with facilitators, a 7–10 hour supervised dosing session with two facilitators, and integration sessions (≈4 hours) post-dose; outcomes assess depressive symptoms to Day 43 and durability over a 1-year follow-up.
Following the 6-week double-blind period all participants enter a 1-year follow-up with regular clinic and phone contacts for symptom, safety, and suicidality monitoring; eligible participants may receive open-label psilocybin 25 mg re-administration under SaS.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Psilocybin 25 mg
experimentalSingle oral 25 mg psilocybin capsule administered with Set and Setting (SaS) protocol (preparation, 7–10 h dosing session, integration).
Interventions
- Psilocybin25 mgvia Oral• single dose• 1 doses total
HPMC capsule; administered with two facilitators in SaS protocol; encouraged headphones/eyeshades; 7–10 h session.
Psilocybin 5 mg
active comparatorSingle oral 5 mg psilocybin capsule administered with Set and Setting (SaS) protocol.
Interventions
- Psilocybin5 mgvia Oral• single dose• 1 doses total
HPMC capsule; active comparator dose.
Inactive Placebo
inactiveSingle oral inactive placebo (MCC 25 mg) capsule administered with Set and Setting (SaS) protocol.
Interventions
- Placebo25 mgvia Oral• single dose• 1 doses total
Microcrystalline cellulose (MCC) 25 mg in HPMC capsule; matched appearance.
Participants
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 Details
- StatusActive not recruiting
- PhasePhase III
- Typeinterventional
- DesignRandomizedtriple Blind
- Target Enrollment240 participants
- TimelineStart: 2024-03-05End: 2026-04-30
- Compounds
- Topic