Psilocybin Treatment for Cannabis Use Disorder

Inclusion Criteria: * ≥ 18 years of age. * Capable of providing written informed consent for participation into the study. * Willingness to allow the study team to review past medical records. * Currently meets criteria for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Cannabis Use Disorder. * Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests. * Concurrent pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening. Allowable bupropion doses for participants will be ≤300mg/day. Exclusion Criteria: * Meeting DSM-5 criteria for another moderate or severe substance use disorder (excluding tobacco) within the past 5 years. * Currently taking antipsychotics, monoamine oxidase (MAO) inhibitors, or antidepressant medications other than SSRIs, SNRIs, or bupropion. Allowable bupropion doses for participants will be ≤300mg/day. * Currently taking lithium or other primary centrally-acting serotonergic medications, whether over-the-counter or prescription (e.g., efavirenz, 5-hydroxytryptophan, St. John's wort). * Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or corrected QT interval (QTc) \> 450 msec), transient ischemic attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic \>139 or diastolic \>89, or heart rate \>90 bpm. * Body weight at screening \<50kg. * Renal disease (creatinine clearance \< 60 ml/min using the Cockraft and Gault equation). * Abnormal screening labs values for hemoglobin, white blood count, creatinine, potassium, and bilirubin outside of the normal lab reference rage. * Transaminases greater than x2 the upper limit of normal lab reference range. * Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I or II Disorder. * Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder. * Epilepsy with history of seizures. * Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia. * Current dementia or related disorders including but not limited to, Alzheimer's Disease, vascular dementia, Lewy body dementia, and frontotemporal disorders. * Current or past major immunosuppressive illness or medications. * Currently pregnant or nursing. * Currently of childbearing potential and not using effective methods of contraception (i.e., intrauterine systems/devices, hormonal methods including implant, shot, patch, ring, or oral contraceptive, condom, diaphragm, sterilization, abstinence, and fertility-awareness methods). * Not fluent in English. * High risk for suicidal ideation or behavior (i.e., individuals who report suicidal ideation with intent or behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) at screening, or individuals with a suicide attempt within the past 3 years).