Abstract
INTRODUCTION: Psilocybin therapy has demonstrated efficacy for cancer-related anxiety and depression, but resource-intensive individual treatment models raise important questions for psychedelic public health about equitable access and scalability. In our prior Phase 1/2 study of group retreat psilocybin therapy for patients with metastatic cancer, we observed partial responders who did not achieve full therapeutic benefit. No published research has examined whether partial responders might benefit from a second psilocybin therapy experience. METHODS: We conducted a single-arm Phase 1 study to assess the safety of a second experience of Group Retreat Psilocybin Therapy for partial responders from our prior study. Protocol modifications addressed dose as a potential contributor to partial response: the initial dose was increased to 35 mg, and an optional 10 mg booster could be requested by participants who reported low subjective effect at 60-90 min and passed a safety check. Pre-retreat antidepressant tapering was not required. The intervention was delivered in a group retreat format with four primary facilitators and included three preparation sessions, a single psilocybin dosing day, and four integration sessions. RESULTS: Thirteen participants (mean age 56 years, 70% female, 38% on concurrent antidepressants) completed the intervention. No serious adverse events occurred; mild adverse events included transient hypertension (n = 4), nausea (n = 3), and headache (n = 1). Seven participants (54%) received the booster dose. Mean Hospital Anxiety and Depression Scale (HADS) Total scores decreased from 15.08 (SD 4.35) at baseline to 9.00 (SD 4.62) at Day +8, with improvements maintained through 24-week follow-up (mean 10.42, SD 6.93); 69% achieved HADS scores below the clinical threshold. The proportion of participants with a "complete" mystical experience (Mystical Experience Questionnaire ≥ 60%) increased from 38% in the first experience to 77% in the second, without an increase in challenging experiences (Challenging Experiences Questionnaire). Social support, social identification, and group cohesion scores showed progressive improvements that persisted at 24 weeks. DISCUSSION: A second experience of group retreat psilocybin therapy was safe and feasible for partial responders with metastatic cancer. The protocol modifications-higher dose, optional booster, and no antidepressant tapering requirement-did not introduce new safety concerns and were associated with substantially enhanced mystical experiences and preliminary efficacy signals. These findings support further investigation of retreatment protocols for partial responders and contribute to developing scalable group-based models relevant to psychedelic public health, where the resource intensity of individual treatment remains a fundamental barrier to population-level access.