Psychedelics for GAD and MDD: Safety Data and Phase 3 Development of DT-120

Jessica Malberg, PhD, and Dan Karlin, MD, presented a poster on the adverse event profile of DT-120, a pharmaceutically optimized formulation of LSD, derived from phase 1 and phase 2b clinical data.¹

Karlin provided context on the broader DT-120 development program, noting that a phase 2b study in 200 participants across 4 dose groups demonstrated a 7.7-point separation from placebo on a generalized anxiety disorder measure following a single dose, with 48% of patients with moderate to severe generalized anxiety disorder achieving full clinical remission at 12 weeks. He described the transition from the powder-capsule formulation used in phase 2b to an oral disintegrating tablet formulation for phase 3, noting that bioavailability studies confirmed pharmacokinetic equivalence, with the added advantages of faster onset of drug effects, slightly longer effect duration, and no increase in clinic time required.² A thorough QT study conducted at doses up to 300 micrograms demonstrated no QT prolongation and no physiological safety signals.

Malberg summarized the pooled adverse event analysis across the three highest doses studied—100, 200, and 300 micrograms. Across all dose levels, approximately 90% of subjective, affective, and perceptual adverse events occurred on the dosing day itself. The most consistently observed adverse events were visual perceptual changes, nausea, and headache, a pattern consistent with findings previously reported in a JAMA publication. On non-dosing days, residual adverse events were predominantly nausea and headache. Karlin concluded that "the drug has predictable and known adverse events, the vast majority of which occur on the day of dosing," framing this profile as clinically manageable and informative for patient counseling.

Four phase 3 studies are currently active, 2 in generalized anxiety disorder and 2 in major depressive disorder, with the first major depressive disorder readout expected by end of the current quarter and 2 generalized anxiety disorder readouts anticipated in the third quarter, Karlin said.

Dr Malberg is executive director of medical affairs at Definium Therapeutics.

Dr Karlin is chief medical officer at Definium Therapeutics.

References

1. Science of DT120. Definium Therapeutics. Accessed May 28, 2026. https://definiumtx.com/pipeline/dt120/

2. A phase 3 trial of DT120 for major depressive disorder (Ascend). Clinical Trials.gov. May 27, 2026. Accessed May 28, 2026. https://clinicaltrials.gov/study/NCT07592689