Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Symptoms of Anxiety and Depression: Safety and Efficacy Outcomes of a Phase 1/2 Study

Background: Psilocybin is a promising therapy for cancer-related distress, but existing individual treatment models are resource intensive. In this study, we designed and tested a group model of psilocybin therapy for people with metastatic cancer and cancer-related anxiety and depression. Method: Eligibility criteria included metastatic cancer, moderate-to-severe symptoms of anxiety or depression without a pre-cancer mental health diagnosis, performance status adequate to attend a 3-day retreat that required self-care, and tapering of antidepressants. Exclusion criteria included enrollment in hospice. The design of the intervention included: two virtual preparatory sessions; a 3-day in-person retreat in a rustic setting that included the third prep session, the psilocybin session, and the first integration session; and two additional virtual integration sessions. Psilocybin was administered in oral capsules at 25 mg. A retreat team of four core facilitators and two backup facilitators conducted a series of eight retreats. The first retreat had five participants. For subsequent retreats, we used the primary safety outcome from each cohort, other safety outcomes, and qualitative feedback to make decisions to increase, decrease, or hold steady the participant number. The primary safety outcome was “unattended episodes of participant distress” during the psilocybin session requiring a backup facilitator. The primary exploratory efficacy outcome was reduction in anxiety and depression symptoms measured using the Hospital Anxiety and Depression Scale (HADS). Results: We enrolled 55 participants, of whom 3 withdrew prior to the retreat, leaving a total of 52. Their mean age was 53, and mean duration of living with cancer was 36 months, mean (range 5, 176); anticancer therapy was ongoing for 46 (88%); antidepressants were tapered for 18 (35%). The first retreat cohort had five participants, and the final retreat cohort had eight. For the primary safety outcome, there was not a single episode of unattended participant distress requiring a backup facilitator. The mean baseline at Day −14 (D −14) HADS total score was 17.5 (range 6-28); at D +28, the mean HADS total score was 10.2 (1-30), so the mean decrease in HADS from D −14 to D +28 was 7.3. ( p < 0.0001). Conclusion: The Group Retreat Psilocybin Therapy was safe and well tolerated, and exploratory measures show efficacy that is promising. A group configuration of eight participants with four core facilitators can be safe for future studies with participants with serious medical illness.