Pragmatic Trial of Psilocybin Therapy in Palliative Care

Inclusion Criteria:

General

* Provision of signed and dated informed consent form and the capacity to consent to research.
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Is currently a patient in a study-engaged clinical site
* Has a life-threatening illness and a life expectancy of ≤2 years
* Has moderate-to-severe demoralization
* Ability to take oral medication (capsules and liquid)

Exclusion Criteria:

General

* Known allergic or severe reactions to the non-psychoactive components of psilocybin capsules or liquid ketamine
* Treatment with another investigational drug or intervention within 1 month of signing Informed Consent Form (ICF)
* If deemed by clinical judgment of the study investigators to be unsafe for undergoing the intervention

Neurological

* Cognitive impairment sufficient to impede the ability to complete study tasks
* History of intracranial hemorrhage
* Recent embolic stroke
* Recent seizure
* Current intracranial mass
* Advanced stage of a neurologic disease that elevates risk for psychosis

Cardiovascular

* Uncontrolled hypertension
* Clinically significant cardiac disease

Respiratory

* Severe pulmonary disease
* Supplemental oxygen requirement

Gastrointestinal

* Current intractable nausea/vomiting/diarrhea
* Recent, clinically significant GI bleed
* Markedly abnormal liver function tests

Endocrine, Renal, and Reproductive

* Pregnancy or lactation
* Severe renal insufficiency
* Unstable insulin-dependent diabetes mellitus

Prohibited Medications

* Antipsychotics (with exceptions)
* Antidepressants (with exceptions)
* Dopamine agonists
* Drugs known to have adverse interactions with psilocybin or ketamine