Published by: New England Journal of Medicine, Nov 2022 (Goodwin et al.)

(NEJM, 2022; COMPASS Pathways Phase 2b)

This large international trial explored psilocybin as a therapy for people who hadn’t responded to standard antidepressants—a group referred to as treatment-resistant depression (TRD). Participants received either a single 25 mg psilocybin dose or a 1 mg control, alongside guided psychological support.

Depression severity was tracked using the Montgomery–Åsberg Depression Rating Scale (MADRS)—a clinician-administered tool that evaluates 10 symptoms including mood, anxiety, sleep, energy, and suicidal thoughts. Scores range from 0 (no symptoms) to 60 (severe depression), and a drop of 6 or more points is typically considered clinically meaningful.

At three weeks, the psilocybin group showed a significantly greater reduction in MADRS scores than the control group, indicating a stronger improvement in mood and emotional regulation. While effects tapered in some participants after several weeks, others maintained benefits longer.

Main findings:

• 25 mg psilocybin led to greater MADRS score reductions vs control.

• More patients achieved clinical response or remission.

• Adverse events were mild and transient (mostly headache, fatigue, or nausea).

• Demonstrates psilocybin’s potential as a rapid-acting intervention for TRD.

Read the study: NEJM — COMPASS TRD trial