RCT of Psilocybin-assisted CBT for Depression

Inclusion Criteria: * Ages 21-60, * Able to swallow capsules, * Patients with a current major depressive episode or a history of major depressive episodes based on the DSM-5 criteria (American Psychiatric Association, 2013), * Active current depressive symptoms (i.e., scores \>16 on the Hamilton-Depression Rating Scale (HAM-D) covering the prior 2 weeks; Hamilton, 1986), * Have an identified support person who can pick up the individual from UCLA Semel Institute and drive individual home following psilocybin sessions, * For women of child-bearing potential - using one form of highly effective contraception (e.g., oral contraceptive pill) and willingness to continue contraceptive use for duration of study * Patient has been medically cleared for the study by a physician. Exclusion Criteria: * A personal or family history (first or second-degree) of psychosis or bipolar disorder * Resting blood pressure above 140 systolic, 90 diastolic (averaged across four separate measurements) * Meeting criteria for a DSM-5 cluster B personality disorder (narcissistic, histrionic, borderline, antisocial personality disorder), * Active suicidality (as indicated by a 3 or greater on item 3 of the HAM-D) or other psychiatric disturbance requiring acute treatment * Current use of antidepressants or other serotonergic-affecting substances (e.g., St. John's Wort and 5-hydroxytryptophan), * Currently receiving cognitive behavioral therapy, * 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 * A history of stroke or Transient Ischemic Attack (TIA) * Epilepsy or history of seizures * Insulin-dependent diabetes * Meeting criteria for a DSM-5 substance abuse or dependence within prior 6 months * Positive urine drug screen for illicit substances * Use of other psychedelics or ketamine within prior 12 months * Adverse prior reaction to a psychedelic agent * Pregnant, trying to get pregnant, or nursing