Palliadelic Treatment (Psilocybin) for the Reduction of Psychological Distress in Patients with Stage IV or Unresectable Gastrointestinal Cancers

Inclusion Criteria

• CANCER PATIENT: Age 19-85
• CANCER PATIENT: 2. Any stage IV or unresectable GI malignancy
• CANCER PATIENT: Residing within 170-mile radius of Omaha, Nebraska
• CANCER PATIENT: Non-zero score on National Comprehensive Cancer Network (NCCN) Distress Thermometer
• CANCER PATIENT: English-speaking
• CANCER PATIENT: Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• CANCER PATIENT: Life expectancy >= 8 weeks as determined by referring oncologist
• CANCER PATIENT: Ability to provide written informed consent and comply with study procedures
• CANCER PATIENT: Aware of the neoplastic and likely incurable nature of his/her disease
• CANCER PATIENT: One family member willing to participate in measures
• CANCER PATIENT: All males and females of childbearing potential (defined as age < 55 and menses within the prior 2 years with intact ovaries and uterus) must be agreeable to use an adequate method of contraception or birth control from the time of enrollment to 24 hours following the psilocybin session
• CANCER PATIENT: Females of childbearing potential must have a negative pregnancy test
• FAMILY MEMBER: A single family member or fictive kin selected by participant will be eligible to participate in the family arm of the study. Should that family member become unavailable at any time, another family member may consented and participate at that time
• FAMILY MEMBER: Age >= 19 years
• FAMILY MEMBER: English-speaking
• FAMILY MEMBER: At least weekly contact with the participant
• FAMILY MEMBER: Ability to provide written informed consent and comply with study procedures

Exclusion Criteria

• CANCER PATIENT: Long-term or unstable psychiatric illness that would prevent safe cessation of psychotropic drugs including monoamine oxidase inhibitor (MAOIs), lithium, or anti-psychotics
• CANCER PATIENT: Severe symptoms of depression or anxiety warranting immediate inpatient evaluation or treatment
• CANCER PATIENT: High-risk of suicide as measured by Columbia Suicide Severity Rating Scale (C-SSRS)
• CANCER PATIENT: Current or prior history of schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder
• CANCER PATIENT: First-degree family member with schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder * Note, exclusions 3 and 4 exists to prevent the possibility that a person with a latent, organic, and usually genetically transmitted psychotic disorder could be prompted into a psychotic episode as a result of the ingestion of the study drug. People who have had transient psychotic symptoms associated with medication or medical illness who do not have personal, or family history of organic psychosis do not have heightened risk
• CANCER PATIENT: Conditions known to be incompatible with establishment of rapport or safe exposure to psilocybin including dissociative disorder, borderline personality, traumatic brain injury, obsessive compulsive disorder, anorexia nervosa, bulimia nervosa, etc. as determined by the principal investigator (PI)
• CANCER PATIENT: Alcohol or recreational drug abuse disorder, excluding caffeine and nicotine
• CANCER PATIENT: Known central nervous system (CNS) metastases or other major CNS disease such as seizure disorder, dementia, Parkinson’s disease, multiple sclerosis. Participants may not have had delirium within 7 days prior to the psilocybin session
• CANCER PATIENT: Receiving treatment in another clinical trial involving an investigational product for the treatment of cancer during the interventional stage of this protocol
• CANCER PATIENT: Advanced hepatic dysfunction as indicated by Child-Pugh score of C (Pugh, 1973)
• CANCER PATIENT: Creatinine clearance < 40 ml/min using the Cockcroft-Gault equation
• CANCER PATIENT: Cardiac or circulatory dysfunction defined as: uncontrolled hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg on three separate readings), angina, stroke or myocardial infarction in the prior 6 months, claudication
• CANCER PATIENT: History of seizures
• CANCER PATIENT: Unable to skip a meal (lunch), or diabetes in a participant who requires administration of medication more than twice daily, or with symptomatic hypoglycemia within the prior 30 days
• CANCER PATIENT: Women who are pregnant or breastfeeding. Females of childbearing potential must have a negative test within 7 days of the psilocybin session
• CANCER PATIENT: Currently using any of the following potent uridine 5′-diphospho (UDP)-glucuronosyltransferases (UGT) metabolic inducers or inhibitors. * Inducers: rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, St. Johns Wort. Paclitaxel, probenecid and dexamethasone are permitted if 5 half-lives have passed between last dose and psilocybin session. * Inhibitors: All Human Immunodeficiency Virus (HIV) protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin
• CANCER PATIENT: MRI exclusions: Metal in body (i.e. hearing aid, cardiac pacemaker, bone plates, braces, non-removeable piercings/implants, etc.) claustrophobia, inability to lay still for one-hour, or any other condition that would preclude MRI scanning