The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder

Exclusion Criteria

• •Patients meeting any of the following criteria are to be excluded from the study:
• •1. Current, past history, or family history, of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).
• •2. Positive Magnetic Resonance screen (e.g., metal implant, claustrophobia, etc).
• •3. Prior electroconvulsive therapy and/or ketamine for current episode.
• •4. Current cognitive behavioral therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of Baseline.
• •5. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening.
• •6. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)49 within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during clinical interview.
• •7. Significant homicide risk as defined by clinical interview.
• •8. Depression secondary to other severe medical conditions.
• •9. Currently taking benzodiazepines daily.
• •10. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as well as exposure to psilocybin or other psychedelics within one year of screening.
• •11. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day Before Psilocybin.
• •12. Cardiovascular conditions: recent stroke (\< 1 year from signing of consent), recent myocardial infarction (\< 1 year from signing of ICF), hypertension (blood pressure \> 140/90 mmHg) or corrected QT interval \> 450 msec) or clinically significant arrhythmia within 1 year of signing the ICF, current anticoagulant therapy, aneurysmal disease.
• •13. Uncontrolled insulin dependent diabetes.
• •14. Seizure disorder.
• •15. Positive urine drug screen for illicit drugs or drugs of abuse (to include but not limited to opiates, phenylcyclohexyl piperidine(PCP), cocaine, amphetamines, methamphetamines, benzodiazepines, barbiturates, and cannabis) at Screening and Day Before Psilocybin. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion.
• •16. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.
• •17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
• •18. Current enrollment in any investigational drug or device study or participation in such within 6 months of Screening.
• •19. Current enrollment in an interventional study for depression or participation in such within 6 months of Screening Visit.
• •20. Non-native speakers of English.