Psilocybin Enhanced Group Psychotherapy in Patients with Cancer, HOPE Study

Inclusion Criteria

• Male or female subject aged >= 25 years old
• Diagnosis of cancer and currently undergoing treatment or completed treatment within =< 26 weeks of study registration
• Life expectancy >= 3 months
• Current Diagnostic and Statistical Manual (DSM)-V diagnosis of a depression disorder including adjustment disorder with disturbance of mood
• Patient Health Questionnaire (PHQ-9) score of >= 10 within 28 days of registration
• Not taking regularly scheduled medications to treat depression and/or anxiety, including benzodiazepines, for at least 4 weeks prior to initiation of the study
• Fluent in English
• Reading literacy and comprehension sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Have a support person that would be able to escort the subject home on the evening of the psilocybin dosing session. However, the use of ride services will not be permitted (e.g., Uber, Lift, taxi, etc.)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless elevated bilirubin is related to Gilbert’s syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional upper limit of normal (ULN)
• For female subjects: Negative pregnancy test and agreement to use highly effective contraception (as described in Section 7.2) or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age: ** Amenorrheic for >= 12 months following cessation of exogenous hormonal treatments; and ** Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or ** Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women >= 50 years of age: ** Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or ** Had radiation-induced menopause with last menses >1 year ago; or ** Had chemotherapy-induced menopause with last menses >1 year ago; or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy)
• For male subjects: agree to condom use during intercourse for 24 hours post-psilocybin dose
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages, ondansetron, cannabis, and non-routine PRN medications within 24 hours of each psilocybin administration. Exceptions include daily use of caffeine, nicotine, and opioid pain medication
• Agree that for one week preceding the psilocybin session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the research team. Exceptions will be evaluated by the research team and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals
• Agree not to use nicotine for at least 2 hours before the psilocybin administration or for the duration of the psilocybin session
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the psilocybin session. If the subject does not routinely consume caffeinated beverages, he or she must agree not to do so on the day of psilocybin administration
• Subjects requiring opioid use for pain are on a stable pain management regimen. Long-acting opioid medications (e.g., oxycodone sustained-release, morphine sustained release) will be allowed if the last dose occurred at least 6 hours before psilocybin administration; such medication will not be taken again until at least 6 hours after psilocybin administration

Exclusion Criteria

• Prior systemic antidepressants, anti-psychotic, or anxiolytic medication within four weeks prior to study initiation
• Personal history or first- or second-degree relatives with schizophrenia, bipolar affective disorder, delusional disorder, schizoaffective disorder, psychosis, or other psychotic spectrum illness
• Currently meeting DSM-V criteria for dissociative disorder, or other psychiatric conditions judged to be incompatible with the establishment of rapport or safe exposure to psilocybin
• Currently meeting DSM-V criteria for cluster B personality disorder
• Current or history within the last two years of meeting DSM-V criteria of substance use disorder (excluding caffeine and nicotine). Current substance use disorders may be identified through the drug urine screening test
• Severe depression requiring immediate standard-of-care treatment (e.g., hospitalization)
• Suicidal ideation over the past month as assessed as a “yes” to question 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale, Suicidal Ideation section
• Cancer with known central nervous system (CNS) involvement, previously treated brain metastasis, or other major CNS disease
• Involvement in another investigational product for the treatment of cancer
• Known paraneoplastic syndrome or other ectopic hormone production by a tumor
• The subject has uncontrolled significant intercurrent or recent illness including, but not limited to, the following conditions: * Cardiovascular disorders: ** Congestive heart failure, including all New York Heart Association Classes. ** Angina pectoris, cardiac hypertrophy, cardiac ischemia, myocardial infarction ** Uncontrolled hypertension at the time of enrollment (blood pressure [BP] > 140 systolic or 90 diastolic), coronary artery disease, artificial heart valve ** Prolonged or congenital long QT syndrome (> 450 ms), serious cardiac arrhythmias, tachycardia, a clinically significant screening electrocardiograph (ECG) abnormality * Renal insufficiency as defined as creatinine clearance < 40 mL/min calculated by Cockcroft-Gault formula * Hepatic disorders: ** Active infection including hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result) or hepatitis C. *** Note: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). * Any other condition that would, in the Investigator’s judgment, contraindicate the subject’s participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [patients may not receive the drug through a feeding tube], social/ psychological issues, etc.)
• Known prior severe hypersensitivity to investigational product or any component in its formulations (National Cancer Institutes [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0 grade >= 3)
• Subjects taking prohibited medications. A washout period of prohibited medications for a period of at least five half-lives should occur prior to study registration