Psilocybin-Assisted Therapy: The Clinical Trial Landscape
Psilocybin-assisted therapy has moved from fringe research to mainstream psychiatric investigation. With two FDA Breakthrough Therapy designations — one for treatment-resistant depression (2018) and another for major depressive disorder (2019) — the compound is now the subject of over 130 registered clinical trials on ClinicalTrials.gov, with more than 100 initiated in the past five years alone.
Who Is Running These Trials?
The field is driven by a mix of academic medical centers and pharmaceutical sponsors:
- COMPASS Pathways (COMP360)
- The furthest advanced program. Their first Phase 3 trial (COMP005) dosed 258 participants across 32 US sites, successfully meeting its primary endpoint for treatment-resistant depression. A second Phase 3 trial (COMP006) spans 96 sites across North America and Europe with 568 planned participants.
- Usona Institute (uAspire)
- A nonprofit running a Phase 3 multicenter trial evaluating psilocybin for major depressive disorder, with sites including Yale and other major academic centers.
- Cybin (CYB003)
- Developing a deuterated psilocybin analog, preparing Phase 3 testing for MDD following FDA consultation.
Key Academic Research Centers
| Institution | Focus Areas | Notable PI |
|---|---|---|
| Johns Hopkins University | Depression, addiction, end-of-life distress | Matthew Johnson, PhD |
| NYU Langone Health | Alcohol use disorder, MDD | Michael Bogenschutz, MD |
| UCSF | Bipolar II, chronic pain, Parkinson's | Joshua Woolley, MD, PhD |
| Yale School of Medicine | OCD, cluster headache, MDD | — |
| Massachusetts General Hospital | Treatment-resistant depression, neuroimaging | — |
Indications Under Investigation
While depression dominates the pipeline, psilocybin trials now cover 54 distinct indications including:
- Treatment-resistant depression and MDD
- Alcohol and opioid use disorders
- Cancer-related anxiety and existential distress
- PTSD and generalized anxiety disorder
- OCD and cluster headache
- Anorexia nervosa and chronic pain syndromes
What to Expect Next
COMPASS Pathways is on track to submit a New Drug Application to the FDA between late 2026 and 2027, which would make COMP360 the first FDA-approved psilocybin therapy. Meanwhile, the number of active trial sites continues to expand as Phase 3 programs recruit across dozens of institutions.