Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy for patients with advanced cancer: protocol for a multi-method feasibility trial

Background: Individuals with advanced cancer often experience high levels of distress for which there are few standardized treatment approaches. Our multidisciplinary team has combined existing evidence-based approaches into Psilocybin-assisted Existential, Attachment, and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose psilocybin session, and integration sessions, with important elements from evidence-based psychotherapies designed for patients with advanced cancer.

Method: This open-label, single-arm clinical trial will assess the acceptability, feasibility, and safety of PEARL therapy among 15 patients with advanced cancer, using qualitative and quantitative methodologies. Participants will complete self-report questionnaires at four time points pre- and post-intervention, as well as a qualitative interview one month after PEARL completion. Feasibility will be evaluated in terms of recruitment, retention, and adherence rates, while safety will be assessed based on the number of participants experiencing no serious adverse events.

Discussion: This study will yield important information about the acceptability and feasibility of PEARL therapy and contribute to growing research around the efficacy of psychedelic-assisted therapies. PEARL therapy has the potential to improve quality of life among those with advanced disease, and careful research is needed to guide public policy, legislation, therapist training, and clinical guidelines.

Trial Registration: NCT06416085; 2024-07-16.