Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder

Depression is common among patients with cancer and is associated with poorer treatment adherence, reduced quality of life, and higher mortality. Earlier pharmacological and psychotherapeutic approaches have shown limited and inconsistent benefits in this population, with some meta-analyses finding no clear superiority of antidepressants over placebo; side effects, delayed onset, and drug interactions further complicate their use in oncology. Psilocybin, a serotonergic 5-HT2A agonist, has emerged as a candidate intervention because it can modulate neural networks implicated in rigid negative cognition and may produce mystical or spiritual experiences that correlate with improved wellbeing. Previous clinical trials have demonstrated safety and antidepressant effects for psilocybin in individual therapy settings and in cancer-associated psychological distress, but conventional delivery models have relied on dyadic care (two therapists per patient), isolated administration settings, and samples mixing anxiety and depressive disorders. Agrawal and colleagues set out to evaluate a novel cohort-based delivery model: psilocybin-assisted therapy administered simultaneously to small groups (cohorts of three to four participants) within a community outpatient cancer centre, combining one-to-one therapist support in individual rooms with group preparation and integration sessions. The study aimed to examine safety, feasibility, tolerability, and preliminary efficacy in patients with curable and noncurable cancer who met criteria for major depressive disorder (MDD). This Phase II, open-label trial tested a single 25-mg psilocybin dose with structured preparatory and integration psychotherapy adapted for the group format.

This was a single-site, Phase II, open-label trial conducted in a community oncology practice. Participants were enrolled in eight cohorts of three to four people between November 2020 and May 2021. Key eligibility screening included the Mini International Neuropsychiatric Interview and the 17-item Hamilton Depression Rating Scale; participants with significant suicide risk (per the Columbia Suicide Severity Rating Scale within the past year or at screening/baseline) were excluded. Prior recreational psychedelic use was allowed if it had occurred more than 12 months before screening. Participants tapered psychiatric medications under medical supervision before the intervention when applicable. The extracted text does not clearly report additional inclusion or exclusion criteria in full. Treatment comprised a single 25-mg oral dose of psilocybin administered simultaneously to cohort members. Therapeutic support included individual sessions (a reported 4.25 hours in a 1:1 therapist–patient ratio) and group sessions (a reported 3.75 hours), with a total of approximately 8 hours of preparation and integration therapy across two preparatory visits, the dosing day, and two postdosing integration sessions. Preparatory work included a 2-hour individual session focused on psychoeducation, coping strategies, and establishing a therapeutic alliance; group preparation and group integration sessions were also provided. During dosing, participants were in individual rooms using eyeshades and a pharmacokinetically timed music programme; one-to-one therapists provided in-room support while two lead clinicians monitored sessions via live video. Participants remained at the facility for 8 hours on dosing day. Safety assessments captured adverse events (AEs) up to 8 weeks postdosing, vital signs, 12-lead ECGs, laboratory tests, and suicidality via C-SSRS. Efficacy was primarily assessed with the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS); response was predefined as ≥50% reduction from baseline and remission as MADRS <10. Additional clinician- and self-rated instruments measured depressive symptoms (QIDS-SR16), anxiety (HAM-A, STAI), pain (pain VAS and EuroQoL pain subscale), demoralization (Demoralization Scale II), disability (Sheehan Disability Scale), quality of life (EQ-5D-5L), psychosocial-spiritual healing (NIH HEALS), and altered states of consciousness (5D-ASC). For analysis, descriptive statistics summarised recruitment, retention, baseline characteristics, and AEs. The Full Analysis Set included all treated participants. Efficacy and exploratory endpoints were analysed with mixed models for repeated measures adjusted for baseline, age, visit, gender, and interactions (baseline-by-visit, age-by-visit, gender-by-visit), with visit as the repeated effect; comparisons with baseline used a two-sided .05 testing level. Effect sizes were reported as Cohen's d. The extracted text indicates no statistical testing was performed for recruitment and retention metrics.