Psilocybin Therapy Clears Second Phase 3 Hurdle for Hard-to-Treat Depression

Treatment-resistant depression — depression that has not responded to multiple standard antidepressants — leaves millions of people searching for options. On 17 February 2026, Compass Pathways announced that COMP360, its proprietary synthetic formulation of psilocybin, succeeded in a second pivotal Phase 3 trial, known as COMP006, bringing a long-studied psychedelic closer to becoming an approved medicine.

In the trial, a single 25 mg dose of COMP360, given with psychological support, was compared against a 1 mg dose three weeks apart. The 25 mg dose produced a highly statistically significant reduction in depression symptoms, with a difference of -3.8 points on the MADRS depression scale (p<0.001) and a rapid onset of effect from the day after administration that was maintained through Week 6. About 39% of participants on the 25 mg dose achieved a clinically meaningful response. Combined with an earlier Phase 3 trial, the company says this is the first time a classic psychedelic has shown consistent, highly significant efficacy across multiple Phase 3 studies in this condition.

“On 17 February 2026, Compass Pathways announced that COMP360, its proprietary synthetic formulation of psilocybin, succeeded in a second pivotal Phase 3 trial, known as COMP006, bringing a long-studied psychedelic closer to becoming an approved medicine.”

The safety findings were reassuring in context. Most treatment-emergent adverse events occurred on dosing days (73%) and resolved within 24 hours (83%), with common side effects including headache, nausea, anxiety and visual changes. Serious adverse events were rare, affecting six of roughly 300 participants. "We are advancing our discussions with the FDA, with the goal of submitting an NDA in Q4," said CEO Kabir Nath, referring to a planned new drug application later in the year.

The usual cautions apply. Psilocybin therapy is delivered with intensive psychological support in a controlled setting, not as a take-home pill, and regulators must still review the full data before any approval. Questions about cost, access and how such treatment would be delivered at scale remain open. But for people whose depression has resisted everything else, a rigorously tested therapy that works quickly and differently from existing drugs is a meaningful source of hope — and a sign that the science of mental-health treatment is genuinely advancing.