Definium's LSD pill eases depression in late-stage trial

Definium Therapeutics’ experimental pill DT120 cleared the main efficacy bar in a phase 3 depression study, posting an 8.1-point placebo-adjusted drop on the Montgomery-Åsberg Depression Rating Scale after six weeks. The result moves DT120 toward an FDA submission, but regulators still must weigh whether the benefit is durable, reproducible and safe enough for broad use.

The Emerge trial enrolled 149 adults ages 18 to 74 at 20 sites, all with DSM-5-confirmed major depressive disorder, a MADRS score of at least 26 and a Clinical Global Impression-Severity score of at least 4 at screening and baseline. Participants received one 100-microgram orally disintegrating tablet, and symptoms improved quickly, with a placebo-adjusted MADRS reduction of 14.2 points at week one and 7.3 points at week 12. The week-six result met the primary endpoint with p<0.0001. Ninety-nine percent of treatment-emergent adverse events were mild to moderate, transient and mostly occurred on the day of dosing, with no serious safety issues and no increase in suicidal thoughts observed. Rob Barrow, Definium’s chief executive, called the results “unprecedented and highly differentiated efficacy” and said the company was moving toward an FDA submission. Stifel said the data exceeded expectations, while Jefferies called the efficacy data “profound.”

On April 18, 2026, President Donald J. Trump signed Executive Order 14401 to remove barriers to psychedelic drugs and other treatments for serious mental illness. The FDA will support development of serotonin-2A agonists and related psychedelic medications after the order. Definium also holds FDA Breakthrough Therapy designation for generalized anxiety disorder, and the company dosed the first patient in Ascend, its second phase 3 pivotal study, on May 11.

Definium shares jumped about 50% to nearly 52% after the announcement, and the company later priced a $700 million upsized public offering to help fund development and possible commercialization.