Psilocybin With Psychotherapy for Improving Chronic Pain in Cancer Patients Requiring Opioids

Inclusion Criteria: * Age ≥ 18 and ≤ 75 years old * Diagnosis of active cancer, any stage * Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Estimated prognosis of ≥ 3 months at the time of enrollment, determined by participant's primary oncologist or palliative physician * Diagnosis of moderate to severe pain (reported average pain score ≥ 4 on the 11-point Numerical Rating Scale) that is chronic (≥ 3 months) and secondary to cancer or cancer treatment * Pain regimen has been escalated to opioid therapy * Participants must be on stable pain regimen for at least one month prior, with no intention to adjust pain regimen during the study period * Participants must be ≥ 4 weeks beyond treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation). Participants may otherwise receive cancer-directed treatment throughout the study period * Have no known procedures/treatments scheduled in advance that would prohibit patient from completing or significantly delaying completion of the study * The participant has no vacations or plans to be out of town during their study enrollment * Participants must not plan for additional treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation) for ≥ 4 weeks following psilocybin treatment initiation. Participants may otherwise receive cancer-directed treatment throughout the study period * No use of other illicit substances (excluding cannabis) within the past year based on self-report at screening and routine urine toxicology screen * Participants must be able to read, write, and speak English * Participants must be able to swallow pills * Agree to refrain from using any unprescribed psychoactive drugs, including alcoholic beverages, ≤ 24 hours of before each psilocybin administration. Exceptions include: * Daily use of caffeine or nicotine * Prescribed benzodiazepine medications and non-benzodiazepine sleeping medications will be allowed to continue through the study period for participants who have been on a stable dose of such a medicine for ≥ 6 weeks prior to screening * Participants using cannabis, including legal cannabis, for any purpose must agree to refrain from use beginning at two weeks before dosing and one week following completion of dosing (7-8 weeks tota…