Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

Inclusion Criteria: i) Veterans or first responders ii) 18 -70 years of age iii) Meets criteria for TRD (current major depressive episode without psychotic features by the Mini-International Neuropsychiatric Interview - MINI, with failure to respond to 2 or more evidence-based anti-depressants in the current episode), iv) Meets moderate to severe use criteria for one primary substance (alcohol, cocaine, opioids/heroin, or cannabis). Moderate to severe co-use of nicotine also acceptable, as well as mild/recreational use of other substances, v) Able to read English and complete study evaluations and consent vi) In good health as verified by screening examination and medical history vii) able to safely receive MRI Exclusion Criteria: i) Exclusionary psychiatric conditions include schizophrenia, schizoaffective disorder, bipolar disorder, current post-traumatic stress disorder, or history of medically serious suicide attempt ii) Actively/imminently suicidal (QIDS-SR question 12 score \>2, Hamilton - depression scale (HAM-D) question 3 score \>3, or Montgomery-Åsberg Depression Rating Scale (MADRS) question 10 \>4) ii) A family history of schizophrenia or schizoaffective disorder (first- or second-degree relatives), or bipolar disorder type 1 (first degree relatives) iii) Use of selective serotonin reuptake inhibitors (SSRIs) and other medications are acceptable if dose has remained stable for 6 months, and is not contra-indicated with psilocybin, as per the study physician, Dr…