Psilocybin Combined With Multidisciplinary Palliative Care in Demoralized Cancer Survivors With Chronic Pain

Inclusion Criteria:

* Signed informed consent form (ICF)
* Diagnosis of solid or liquid cancer made \>= 1 year at any stage in cancer survivorship (specifically, active cancer treatment or no cancer-directed therapy either in clinical remission or with advanced disease)
* Prognosis of greater than six months as determined by their primary oncologist
* Moderate-to-severe demoralization (score of \>= 10 on the Demoralization Scale-II \[DS-II\])
* Chronic pain (pain lasting \> 3 months) per patient report and score of \>= 5 for average pain level on Brief Pain Inventory
* Age \>= 26 years old and ≤85 years old
* Availability of a friend or family member into whose care the participant can be released following the drug administration session

Exclusion Criteria:

* Pregnancy or breastfeeding
* Women of childbearing potential (i.e., not permanently sterilized, not postmenopausal) who decline to use a highly effective dual contraceptive method for the duration of the study. Dual contraceptive method use is defined by a use a barrier contraceptive in addition to another method to prevent pregnancy, including sterilization, hormonal methods, intrauterine devices, and hormonal pills.
* Age \< 26 years old and \> 85 years old
* Poor functional status (Eastern Cooperative Oncology Group \[ECOG\] score of \>= 2)
* Major cognitive impairment as determined by principal investigator
* Non-fluency in the English language
* Personal history of a psychotic disorder or Bipolar disorder type I/II
* Active suicidal ideation with intent in the last 3 months (Columbia Suicide Severity Rating Scale suicidal ideation score \> 3) or any suicide attempt in the past year
* Current substance use disorder (i.e., present in last six months), of greater than mild severity as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
* History of a seizure disorder in adulthood
* Active central nervous system (CNS) metastases or symptomatic CNS infection
* Uncontrolled hypertension (mean blood pressure (mmHg) exceeding 139 systolic and 89 diastolic) and heart rate exceeding 90 beats per minute
* Clinically significant cardiovascular disease (coronary artery disease, congestive heart failure, arrhythmia, or QTc\>450ms)
* Supplemental oxygen requirement
* Body mass index =\< 18
* Renal insufficiency as evidenced by creatinine clearance (CrCl) \< 30 mL/min
* Concomitant use of drugs known to interact with psilocybin (probenecid, diclofenac)
* Consistent use of serotonergic drugs including selective serotonin reuptake inhibitors (SSRIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), or efavirenz, as well as monoamine oxidase inhibitors (MAOIs). Subjects using any other antidepressant, stimulant, or antipsychotic medications on Day 0 (baseline visit) may be allowed to enroll in the study if they elect to taper off the medications under medical supervision by the PI and the study psycho-oncologist (PO) by the day prior to the baseline visit
* Considered by the principal investigator to be inappropriate for the study due to safety concerns or to be unlikely to complete the protocol