Psilocybin-Assisted Therapy in Treatment-Resistant Depression

Eligibility Criteria

• * Provision of signed and dated informed consent form.
• * Willingness to comply with all study procedures and availability for the study.
• * Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-V) diagnosis of major depressive disorder.
• * Currently experiencing a major depressive episode, lasting at least 3 months
• * Failure to respond or inability to tolerate at least 2 guideline-concordant pharmacological treatments from different pharmacologic classes during the current major depressive episode
• * Good health evidenced by medical history and routine lab tests
• * No central nervous system (CNS) or neurocognitive impairment
• * Ability to take oral medication and to follow to the psilocybin-assisted therapy protocol
• * Identified support person to accompany patient home after dosing
• * Use of effective contraception throughout the study by those with child-bearing potential
• * Use of condoms or other effective contraceptive methods by males with reproductive potential
• * Fully vaccinated and up to date on vaccination against COVID-19, as defined by Center for Disease Control guidelines
• * Following Lifestyle Considerations throughout study (no nicotine containing products in clinical unit, refrain from operating heavy machinery for the duration of treatment day, no more than two servings 8 hours prior to treatment, no psychoactive drugs 72 hours before treatment, refrain from consuming foods that would interfere with drug absorption, minimize interaction with household immunocompromised contacts)
• * Family history (first- or second-degree relatives) or diagnosis of bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, hallucinogen-induced psychosis, anti-social personality disorder, or other psychotic disorder.
• * Borderline personality disorder, defined by DSM-V criteria, that in the judgement of the Investigator is likely to complicate the assessment of clinical response to study treatments or limits the patient's ability to comply with study procedures.
• * Alcohol or other substance use disorder (except tobacco/nicotine) that has been active within the 6 months prior to enrollment.
• * Recent use (within past 6 months) of esketamine, ketamine or classic hallucinogens (psilocybin-containing mushrooms or LSD) or use of psychedelics more than 10 times in lifetime.
• * Participants with active suicidal ideation or plan with a Columbia Suicide Severity Rating Scale (C-SSRS) score greater than or equal to 4.
• * Current active self-injurious behavior, requiring medical attention or per investigator discretion.
• * Diagnosis of Obsessive-compulsive disorder or post-traumatic stress disorder.
• * Within 72 hours of psilocybin administration, use of nicotine, alcohol, or other controlled substances.
• * Current delirium, dementia, amnestic disorder, or other cognitive disorders.
• * Any current or past medical or neurological illness (including chronic pain syndromes and/or history of cerebrovascular event (excluding migraine)) that, in the opinion of the investigator, may confound the interpretation of study assessments
• * Known allergic reactions to components of psilocybin.
• * Medically instability at screening, including hepatic, renal, circulatory, cardiac (arrhythmia, uncontrolled hypertension, systolic BP \> 140 mmHg or diastolic BP \> 90 mmHg, abnormal QTc), pulmonary or CNS (seizure disorder or treatment with antiepileptic drugs) impairment.
• * Current pregnancy or lactation.
• * Febrile illness in last 3 weeks.
• * Current use or use within 4 weeks of psilocybin administration of Monoamine oxidase inhibitors (MAOIs), alcohol dehydrogenase inhibitors and antipsychotics (concomitant medications will be allowed per investigator discretion).
• * Current treatment with buproprion greater than 300mg/day.
• * Current use of tramadol.
• * Prior participation in psilocybin-assisted therapy trial and or regular use of hallucinogens
• * Treatment with another investigational drug or other intervention during study period.