Imperial College vs COMPASS Pathways trial designs — key differences?

Key differences: Imperial (Carhart-Harris group, now at UCSF) does academic/NHS research primarily on treatment-resistant depression, using naturalistic facilitation with trained therapists in prepared psychedelic sessions. Doses typically 10mg and 25mg pure psilocybin. Results from their 2021 NEJM paper showed psilocybin comparable to escitalopram at 6 weeks. COMPASS Pathways is a for-profit pharma company developing COMP360 (synthetic psilocybin) as a drug product. Phase 2b trial (published 2022, NEJM) used 1mg, 10mg, and 25mg doses; 25mg showed significant antidepressant effect at 3 weeks. Their model is more standardised/manualized — designed for regulatory approval, not naturalistic therapy.

The facilitation model difference matters: COMPASS uses a more psychotherapy-lite approach (psychological support rather than full psychotherapy), Imperial/MAPS models involve more extensive therapy. The debate in the field is whether the therapeutic relationship and preparation/integration are part of the medicine or administrative overhead. FDA and EMA will probably require both the drug and the therapy to be tested as a package.

Both programs use pure synthetic psilocybin, not mushrooms. This matters for regulatory purposes and for dose precision. The mushroom vs synthetic debate is relevant in Oregon/Colorado (which use natural psilocybin products in service centers) vs what a potential FDA-approved drug would look like.