Inclusion Criteria:  For participants with a diagnosis unresectable pancreatic or biliary tract cancer (gallbladder adenocarcinoma, cholangiocarcinoma, ampullary adenocarcinoma carcinoma), do they have a non-zero score on the NCCN Distress Thermometer? Record Distress score ___________ Is the participant between the ages of 19 and 85? Record age: ________ Does the subject have unresectable pancreatic or biliary tract cancer (gallbladder adenocarcinoma, cholangiocarcinoma, ampullary adenocarcinoma carcinoma)? Is the participant English speaking? Does the participant have an ECOG performance status of 0-3? Score:______ Does the participant have a life expectancy ≥ 8 weeks as determined by referring oncologist? Does the participant have the ability to provide written informed consent and comply with study procedures? Is the participant aware of the neoplastic and likely incurable nature of his/her disease? Does the participant have one family member willing to participate in measures? Is the participant (male and female) of childbearing potential (defined as age <55 and menses within the prior 2 years with intact ovaries and uterus) agreeable to use an adequate method of contraception or birth control from the time of enrollment to 24 hours following the psilocybin session?  Exclusion Criteria:  Does the participant have severe symptoms of depression or anxiety warranting immediate treatment with antidepressant or anxiolytic medications or preventing safe discontinuation of those medications for the psilocybin session? Is the participant suicidal, noted by a history of suicide attempt within 2 years or high-risk of suicide as measured by Columbia Suicide Severity? C-SSRS score:_______ Does the participant have a current or prior history of schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder? Does the participant have a first-degree family member with schizophrenia, psychotic disorder (unless substance induced or due to medical condition) or bipolar I or II disorder? Does the participant have any conditions known to be incompatible with establishment of rapport or safe exposure to psilocybin including dissociative disorder, anorexia nervosa, bulimia nervosa? Does the participant have alcohol or recreational drug abuse disorder, excluding caffeine and nicotine? Does the participant have known CNS metastases or other major CNS disease such as seizure disorder, dementia, Parkinson's disease, multiple sclerosis? Is the participant receiving treatment in another clinical trial involving an investigational product for the treatment of cancer? Does the participant have Hepatic dysfunction as indicated by the following values: Alkaline phosphatase: _____ AST: _____ ALT:_____ Total bilirubin: ________ NOTE: Participants with baseline hepatic dysfunction which their treating physician expects will improve to meet the criteria defined above following cancer treatment and/or other intervention (ie. biliary stent) are eligible; the above criteria must be met prior to administration of psilocybin Does the participant have Renal dysfunction as indicated by creatinine clearance <40 ml/min using the Cockroft-Gault equation? Creat. Clr: ______ Does the participant have 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? Does the participant have a history of seizures? Is the participant unable to skip a meal (lunch), or diabetes which requires administration of medication more than twice daily, or with symptomatic hypoglycemia within the prior 30 days? Female participants only: Is the participant pregnant or breastfeeding? Pregnancy test date: __________ Result: ________ Is the participant currently using any of the following potent metabolic inducers or inhibitors? Inducers: rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, St. Johns Wort. Paclitaxel and dexamethasone are permitted if 5 half-lives have passed between last dose and psilocybin session Inhibitors: All HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin MMRI 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?