Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression

Inclusion Criteria: * Veteran of the U.S. military who is English-speaking * Signed informed consent and HIPAA * Adults \</= 75 years of age * Meets DSM-5 criteria for current major depressive episode (MDE) * MADRS \>/= 20 at baseline * Failure to respond satisfactorily to \>/= 2 antidepressant treatments for \>/= 8 weeks, including \>/= 2 weeks at an adequate dose (\>/= 50% of the FDA-approved uppermost dose) for major depression. Augmentation with a medication for depression (e.g., neuroleptics, lithium, levothyroxine) is considered a separate course of treatment. * If applicable, concurrent \& permitted antidepressants must be at stable doses for \>/= 4 weeks prior to baseline (see allowed \& prohibited medication list) * Participants of child-bearing potential must have negative pregnancy test \& agree to adhere to a medically acceptable method of birth control during the study * Has a responsible adult who will provide transportation to the participant's home or place of lodging on the days of psilocybin administration Exclusion Criteria: Exclusion Criteria: * Lifetime bipolar, schizophrenia spectrum, or other psychotic disorders * First-degree relative with history of bipolar I, schizophrenia spectrum or other psychotic disorder * Presence of psychotic symptoms (e.g., MDE with psychotic symptoms) * Sedative-hypnotic, stimulant, inhalant and/or opioid use disorder within past 6 months (lifetime substance use disorder is allowed at the discretion of the LSI) * Severe …