Overview
This multicenter, triple-blind, phase 2, randomized controlled trial will evaluate the efficacy and safety of psilocybin therapy compared to an active control in treating demoralization in adults near the end of life (≤2 years life expectancy).
Description
After providing written informed consent, participants deemed eligible for this trial will be randomized to a brief course of talk therapy plus 1 dose of oral psilocybin vs the same brief course of talk therapy plus 1 dose of oral ketamine (the active control). Participants' degree of demoralization and other clinical outcomes (e.g., depression, anxiety) will be assessed at 1, 2, and 5 weeks after the study drug administration. After completing the study, participants will have the option of being told which study drug they took (aka, "unblinded"); those who were randomized to the active control will be offered another brief course of talk therapy plus 1 dose of oral psilocybin, and the same sequence of outcome assessments.
Eligibility
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