A single dose of LSD reduced symptoms of generalized anxiety disorder for at least 12 weeks in a large Phase 3 trial, according to topline results released by Definium Therapeutics on August 12.
The Voyage trial included 214 adults aged 18 to 74 at approximately 35 sites across the United States. Participants received either 100 micrograms of DT120 — the company’s fast-dissolving pharmaceutical formulation of LSD, also known as lysergide — or an identical-looking placebo. The dose was given once in a supervised session.
The main measure was the Hamilton Anxiety Rating Scale, a standard clinician-rated questionnaire. After 12 weeks, scores had fallen by an average of 11.6 points in the LSD group and 6.2 points in the placebo group. That produced a 5.4-point difference in favor of DT120.
The effect appeared quickly. On a separate clinician-rated severity scale, the company reported a significant difference by the second day, which remained throughout the 12-week study. By week 12, 43% of those given DT120 had experienced at least a 50% reduction in symptoms, compared with 16% of the placebo group. Remission rates were 14% and 4%, respectively.
Definium said side effects were generally mild or moderate, temporary and concentrated on the dosing day. Participants met the study’s criteria for ending the supervised session after an average of 6.4 hours, and 92% did so within eight hours. The company reported no new safety signal and no increase in suicidal thoughts or behavior.
The result is Definium’s second positive Phase 3 readout this year, following its Emerge study in major depressive disorder in June. DT120 holds Breakthrough Therapy designation from the FDA for generalized anxiety disorder.
The result is impressive, but it has not yet appeared in a peer-reviewed paper. Only summary figures selected and released by the company are currently available.
Blinding is another important question. A full 100-microgram dose of LSD produces noticeable effects, making it difficult to conceal who received the drug. Definium’s second Phase 3 anxiety trial includes a 50-microgram group intended to make treatment assignments harder to guess. Results are expected in September.
If that trial confirms Voyage, DT120 will move closer to becoming the first LSD-based treatment approved for generalized anxiety disorder. It would be administered as a precisely measured medicine in a supervised clinical setting, not used as an everyday anxiety drug.
