MB-PAT for Demoralization in Advanced Cancer ('PAT-MIND') Trial

Inclusion Criteria:

* Written informed consent provided before any study-specific procedures.
* Age 18 years or older.
* Diagnosis of advanced cancer: Stage III-IV or metastatic solid tumor. Stage II cancer may be eligible if the treating oncologist confirms advanced/refractory disease with clinically significant existential burden, defined as a Demoralization Scale-II (DS-II) score ≥11.
* Clinical life expectancy of at least 6 months. Borderline cases of approximately 5-6 months may be considered based on Principal Investigator judgment and documentation.
* Demoralization Scale-II (DS-II) total score ≥4 at screening, or DS-II total score ≥3 with documented clinical impression of significant existential distress.
* Willing and cognitively able to complete at least 2 preparation sessions, 1 in-person dosing session, and at least 2 integration sessions over approximately 6-8 weeks.
* Sufficient spoken and written English proficiency to provide informed consent, participate in group therapy, and complete participant-reported outcome measures.
* Not pregnant or lactating. Participants of childbearing potential must have a negative pregnancy test at screening and comply with protocol-specified contraception requirements.
* A responsible adult, such as a family member, friend, or caregiver, must be available to accompany the participant or be on-call for at least 12 hours following the dosing session.

Exclusion Criteria:

Psychiatric/Psychological:

* Active or high-risk suicidality, defined as Columbia-Suicide Severity Rating Scale (C-SSRS) item 4 or 5 within the past 4 weeks, or a suicide attempt within the past 12 months. Passive death wishes and suicidal ideation without intent are not exclusionary.
* Current psychotic disorder or active psychotic symptoms, including schizophrenia, schizoaffective disorder, hallucinations, delusions, or thought disorganization. Historical psychosis in sustained remission may be considered on a case-by-case basis by the Principal Investigator.
* Current manic or mixed-state episode. Stable, euthymic bipolar disorder on maintenance pharmacotherapy may be permitted with Principal Investigator judgment and documentation.
* Moderate-to-severe active alcohol, stimulant, or opioid use disorder within the past 12 months. Severe uncontrolled cannabis use disorder is exclusionary; stable prescribed cannabis use is permitted.

Pharmacological/Drug Interactions:

* Use of concomitant medications that does not meet the requirements of the protocol-specified Concomitant Medications Policy.
* Known allergy, anaphylaxis, or serious hypersensitivity to psilocybin, psilocin, related tryptamines, or capsule excipients.

Medical:

* Severe hepatic impairment, defined as a current unstable diagnosis of liver disease with AST or ALT \>5 times the upper limit of normal and clinical symptoms.
* Severe renal impairment, including current unstable acute kidney injury or advanced kidney disease (CKD Stage 4) with eGFR \<30 mL/min/1.73 m².
* Unstable cardiovascular disease, including myocardial infarction or stroke within the past 3 months, decompensated heart failure (NYHA III-IV), or uncontrolled arrhythmia. Elevated blood pressure on dosing day may require dosing deferral and reassessment according to protocol-defined thresholds.
* Seizure within the past 12 months or currently uncontrolled epilepsy. Well-controlled epilepsy with no seizures for more than 12 months on stable therapy may be permitted with monitoring.
* Uncontrolled diabetes, including unstable Type 1 diabetes with diabetic ketoacidosis within the past 3 months, or Type 2 diabetes with HbA1c \>11% and symptomatic hyperglycemia.
* Any medical, neurological, or psychiatric condition, or concurrent cancer-directed therapy, that in the Principal Investigator's clinical judgment would materially increase risk or prevent meaningful protocol participation.

Cancer Treatment-Related:

* Systemic anti-cancer therapy that does not meet protocol requirements. Chemotherapy, immunotherapy, and targeted therapy are permitted when the regimen is stable, treatment-related toxicities are CTCAE Grade 2 or lower, and protocol-specified timing requirements before psilocybin dosing are met.
* Opioid analgesic or corticosteroid use that does not meet protocol requirements. Opioids must be on a stable dose for at least 1 week without opioid-induced delirium or clinically significant respiratory compromise. Corticosteroids must generally be stable for at least 2 weeks; high-dose dexamethasone for acute central nervous system edema requires dosing to be deferred until clinically stable.