Trial PaperAnxiety DisordersDepressive DisordersSuicidalityMajor Depressive Disorder (MDD)Chronic PainHeadache Disorders (Cluster & Migraine)Palliative & End-of-Life DistressSafety & Risk ManagementPsilocybin

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

In a phase 2 open‑label trial, a single 25 mg dose of psilocybin given in a group therapy setting with one‑to‑one therapist support was safe and feasible in 30 patients with cancer and major depressive disorder, with no psilocybin‑related serious adverse events. The treatment produced a large reduction in depressive symptoms (mean 19.1‑point decrease; 80% sustained response; 50% remission at week 1 maintained through 8 weeks), suggesting clinical efficacy warranting further study.

Authors

  • William Richards
  • Manish Agrawal
  • Yvan Beaussant

Published

Cancer
individual Study

Abstract

Background

Depression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin‐assisted therapy in patients with cancer and major depressive disorder.

Methods

This phase 2, open‐label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25‐mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist‐to‐patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability.

Results

Thirty participants completed the study. No psilocybin‐related serious adverse events occurred; treatment‐related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to –16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks.

Conclusions

Psilocybin‐assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group‐oriented format, compact delivery time, community cancer center setting, and one‐to‐one therapist‐to‐patient ratio could also add to therapeutic gains and efficiency of administration.

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Research Summary of 'Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder'

Introduction

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.

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Study Details

References (12)

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