Safety and Efficacy of Psilocybin During Anticancer Treatment: A Phase II Trial Secondary Analysis.

CONTEXT Psilocybin-assisted therapy has demonstrated rapid antidepressant effects in patients with cancer, but most trials have excluded individuals receiving active systemic anticancer treatment, limiting safety data in this population.

Objectives: To compare the efficacy and safety of psilocybin-assisted therapy in patients receiving versus not receiving concurrent systemic anticancer treatment.

Methods: This secondary analysis used data from a phase 2, open-label, single-arm trial (NCT04593563). Adults with malignant neoplasms and DSM-5-diagnosed major depressive disorder received individual and group preparation therapy, a single 25-mg oral psilocybin group dosing session, and individual and group integration therapy. Active systemic anticancer treatment was defined as receipt of systemic therapy within 30 days of psilocybin dosing (systemic treatment, n=17; no systemic treatment, n=13). The primary outcome was between-group difference in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at weeks 1, 3, and 8; secondary outcomes included adverse events (AEs), severity, and timing through week 8.

Results: Among 30 participants (mean [SD] age, 56 [12] years; 21 women [70%]), MADRS scores decreased substantially in both groups, with no significant between-group differences at week 1 (P=.88), week 3 (P=.93), or week 8 (P=.97). AEs were frequent in both groups (mean per participant, 9.0 vs 6.7; P=.08). Four severe AEs and one serious AE occurred, all in systemic treatment recipients, but were deemed unrelated to psilocybin. No significant laboratory or suicidality changes attributable to psilocybin were observed.

Conclusion: Psilocybin-assisted therapy had comparable antidepressant outcomes and a similar safety profile in cancer patients regardless of systemic anticancer treatment status, supporting inclusion of actively treated oncology populations in future psilocybin trials.