LYSERGIDE TARTRATE (LSD; DT120) SAFETY PROFILE FROM PHASE 1 AND PHASE 2 CLINICAL STUDIES

The aim of this analysis is to characterize the safety profile of Lysergide Tartrate (LSD; DT120) at the 100 and 200mcg dose range across studies, emphasizing the timing and nature of adverse events (AEs) to better inform its clinical utility. Lysergide Tartrate (LSD: DT120) is an investigational compound under development for the treatment of generalized anxiety disorder (GAD) and major depressive disorder (MDD), using a single-dose paradigm. Unlike the current standard of care for GAD and MDD, which requires daily medication dosing with resultant persistent adverse event (AE) burden, DT120 is being clinically evaluated as a potential treatment option with improved rapidity of onset, magnitude of efficacy, prolonged durability, and a favorable tolerability profile.

Methods

These safety data were derived from three studies that included 171 adult participants: two Phase 1 open-label, randomized, 2-period, 2-sequence, crossover studies evaluating DT120 100 µg in 27 and 64 participants. A single Phase 2 multicenter, randomized, double-blind, placebo-controlled study evaluating 100 and 200 µg (n=40 per treatment group). Treatmentemergent adverse events (TEAEs), vital signs, and suicidality (Columbia–Suicide Severity Rating Scale) were monitored and reported. TEAEs were coded using MedDRA (v26.0) and categorized as occurring either within 24 hours of dosing or more than 24 hours after dosing. For each AE, severity and relatedness to treatment were determined.

Results

In the Phase 1 studies, > 75% of participants experienced TEAEs. Most TEAEs occurred on dosing day and were consistent with the known acute pharmacodynamic profile of DT120. The most frequently reported TEAEs across the Phase 1 studies were mydriasis, visual hallucinations, euphoric mood, and illusions at similar rates across the cohorts. In the Phase 2b study, TEAEs were reported in 97.5% of participants with DT120 100 µg and 92.5% with DT120 200 µg. The majority of TAES occurred on the dosing day and were mild to moderate. The most common adverse events were visual perceptual changes (illusion, pseudo-hallucination and visual hallucination), nausea, headache, euphoric mood, anxiety, mydriasis, and not clinically significant increases in blood pressure. Post-treatment TEAEs occurred in approximately 56% of participants in both groups; the most common were headache, fatigue, low mood, and insomnia. These were comparable to placebo at 38.5%. Related serious adverse events (SAEs), hallucinogen persisting perception disorder, or deaths were not observed. No participants engaged in self-injurious or suicidal behavior, which was assessed using the C-SSRS and AE reporting. There were no reports of suicidal ideation with intent or a plan during the sessions or through the trial. Participants with a history of suicidal ideation showed no increase in severity. Vital sign changes did not reach clinical significance or require intervention.

Conclusions

In the three studies that included 171 eligible participants, a single administration of DT120 100 or 200 µg was characterized by transient sensory-perceptual and physiological effects, largely confined to the dosing day. The majority of TEAEs on dosing day were rated mild to moderate. Across studies, post-treatment TEAEs were uncommon and mild. No suicidality signal was observed. No cumulative or study-wide safety trends emerged. These findings demonstrate a consistent safety profile across studies, supporting further clinical evaluation of DT120.