Psychedelics & Consciousness
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Goodwin et al. · 2022 · New England Journal of Medicine
Multi-site dose-finding Phase 2b trial of a single psilocybin dose in treatment-resistant depression.
Research objective
Determine the efficacy of a single 25 mg, 10 mg, or 1 mg dose of synthetic psilocybin in patients who had failed multiple antidepressants.
Methodology
Randomized double-blind trial in 233 patients across 22 sites. Primary outcome: MADRS change at week 3. Psychological support before, during, and after dosing was standardized.
Key findings
- 25 mg arm produced significantly greater MADRS reduction than 1 mg control at week 3.
- Effects persisted in a subset of patients through week 12.
- Serious adverse events including suicidal ideation occurred across arms; rigorous safety monitoring was emphasized.
Strengths
- Largest controlled trial of psilocybin to date at the time of publication.
- Standardized synthetic compound and protocol.
Limitations
- Durability beyond 12 weeks not established by this trial.
- Functional unblinding remained an issue.
Practical implications
- Provided the regulatory dataset enabling further Phase 3 development.
- Highlighted the need for ongoing safety monitoring even in carefully selected populations.
Related entities
Related research
Trial of Psilocybin versus Escitalopram for Depression
Head-to-head Phase 2 trial comparing psilocybin-assisted therapy with a standard SSRI in moderate-to-severe depression.
Read summary
MDMA-Assisted Therapy for Severe PTSD: A Phase 3 Randomized Trial
First Phase 3 RCT of MDMA-assisted therapy for post-traumatic stress disorder.
Read summary
REBUS and the Anarchic Brain
Theoretical synthesis proposing that psychedelics work by relaxing high-level priors in a hierarchical predictive brain.
Read summary
Sustained Rescue of Prefrontal Circuit Dysfunction by Antidepressant-Induced Spine Formation
Two-photon imaging in mice showing rapid dendritic spine formation after ketamine and its causal role in sustained behavioral rescue.
Read summary