Multicenter, quadruple-blind, Phase II randomized controlled trial (n=100) comparing a single oral dose of psilocybin plus brief existential psychotherapy versus a single oral dose of ketamine plus the same psychotherapy for demoralization in patients near end of life (≤2 years expected).
Parallel-group randomized trial assigning participants to one single oral dose of psilocybin plus 4–5 sessions of brief existential psychotherapy or to one single oral dose of oral ketamine plus the same psychotherapy; control arm may optionally crossover.
Primary outcomes assess change in demoralization; secondary measures include depression and anxiety at 1, 2 and 5 weeks post-dosing. After study completion participants may be unblinded and those assigned to the active control are offered psilocybin plus psychotherapy.
Population: adults with life-threatening illness receiving care at participating sites with expected survival ≤2 years and moderate-to-severe demoralization; ability to take oral medication required.
Single oral psilocybin dose plus 4–5 sessions of brief existential psychotherapy; parallel design with optional crossover for control arm.
Dose not specified in registry record.
Single oral ketamine dose (active control) plus 4–5 sessions of brief existential psychotherapy; optional crossover for control arm.
Oral liquid ketamine; dose not specified in registry record.