Psilocybin Therapy Clears Second Phase 3 Hurdle for Hard-to-Treat Depression
On 17 February 2026, Compass Pathways reported that its second Phase 3 trial of COMP360 psilocybin met its primary endpoint, with two 25 mg doses significantly reducing symptoms of treatment-resistant depression and rapid onset from the next day.
HealthGNGV Editorial Team4 min read
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, two 25 mg doses of COMP360, given with psychological support three weeks apart, were compared against 1 mg doses. 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.
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.
