Psilocybin shows promise in relieving depression in cancer patients

The 5-HT_2A receptor agonist psilocybin, when taken under medical supervision, may offer a promising approach to treatment of major depressive disorder (MDD) in cancer patients, results of a small phase II study suggest.

In a single-centre, fixed-dose, open-label phase II study, 30 adult patients (mean age, 56 years; female, 70 percent) with curable cancer (n=14; 47 percent) or incurable metastatic cancer (n=16; 53 percent) who were diagnosed with MDD (baseline mean Montgomery-Asberg Depression Rating Scale [MADRS] score, 25.9) were recruited at Aquilino Cancer Center, Rockville, Maryland, US. At baseline, 12 patients (40 percent) had had >3 depressive episodes, while nine patients (30 percent) had had ≤3 depressive episodes. Half of the patients had used antidepressants previously. [JAMA Oncol 2023;doi:10.1001/jamaoncol.2023.0351]

Psilocybin (COMP360) treatment was administered as a 25 mg single dose, in a 1-to-1 therapist-to-patient ratio, simultaneously to cohorts of 3–4 patients in adjacent rooms open to a common space at a community cancer centre. The cohorts of patients also received group therapy (one preparation session and two integration sessions), which was supplemented by individual therapy.

Results showed a robust reduction in MADRS scores of 19.1 points from baseline at week 8 (p<0.001). Notably, 50 percent of patients achieved full remission of depressive symptoms and 80 percent had a sustained response at 8 weeks.

The patients’ self-reported depressive symptoms showed a 48 percent reduction from baseline at week 8, while self-rated depression severity showed a 53 percent decrease.

Adverse events (AEs) in the study were mild or expected, and included headache (n=24), nausea (n=12), altered mood (n=8), anxiety (n=7), and hallucinations (n=1). No treatment-related serious AEs or suicidality were reported.

“To our knowledge, this is the first psilocybin therapy trial conducted in a community cancer centre setting rather than at a psychiatric hospital or academic centre setting,” the researchers noted.

“Participants experienced clinically meaningful, rapid, and sustained improvement in symptoms of depression over 8 weeks following a single [administration] of psilocybin therapy. This occurred both in patients with curable cancer and in those with metastatic cancer,” they continued. “Comparison with placebo and other antidepressant treatments for patients with cancer is needed … justifying a randomized clinical trial.”