720. Unraveling anxiolytic and anti-addictive properties of lysergic acid diethylamide in a model of alcohol use disorder
Todd M Solomon, Robert Barrow, Daniel R Karlin, P Jacobsen, Jamie M Freedman
International Journal of Neuropsychopharmacology September 9, 2026 DOI: 10.1093/ijnp/pyag040.492 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 2b, multicenter, randomized, double-blind, placebo-controlled trial Peer reviewed |
|---|---|
| Sample size | 198 |
| Population | Adults aged 18 to 74 years with a primary diagnosis of moderate to severe generalized anxiety disorder (HAM-A score ≥20), enrolled at 22 US outpatient psychiatric research sites |
| Intervention | MM120 (lysergide D-tartrate) |
| Dose | single freebase-equivalent dose of 25 μg, 50 μg, 100 μg, or 200 μg |
| Duration | Single-dose intervention; primary outcome assessed at 4 weeks; last follow-up November 27, 2023 |
| Measures | Hamilton Anxiety Rating Scale (HAM-A), multiple comparison procedure modeling (MCP-Mod) |
| Topics | Addiction LSD |
| Key findings | A single dose of MM120 produced a dose-dependent reduction in anxiety at week 4: the 100 μg and 200 μg doses significantly reduced HAM-A scores versus placebo (least-squares mean differences of −5.0 and −6.0 points), while 25 μg and 50 μg did not. The authors conclude these results support dose-dependent efficacy and inform dose selection for phase 3 trials. |
Abstract
Abstract Background Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed. Aims & Objectives To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD.
Method: This phase 2b, multicenter, randomized, double-blind, placebo-controlled study enrolled 198 adults aged 18 to 74 years with a primary GAD diagnosis who presented with moderate to severe symptoms (defined by a Hamilton Anxiety Rating Scale [HAM-A] score 20) and was conducted at 22 outpatient psychiatric research sites in the US from August 2022 to August 2023. The anxiety and depression end point assessments were conducted by independent central raters who were blinded to the trial protocol, treatment allocation, and study visit date. The last date of follow-up was November 27, 2023. Participants were randomized to receive a single (freebase equivalent) treatment dose with 25 μg (n = 39), 50 μg (n = 40), 100 μg (n = 40), or 200 μg (n = 40) of MM120 or placebo (n = 39). The primary outcome was a dose-response relationship assessed using the multiple comparison procedure modeling (MCP-Mod) method for change in HAM-A score at 4 weeks (score range, 0-56; higher scores indicate greater severity; 7 indicates no or minimal anxiety; 8-14, mild; 15-23, moderate; and 24, severe). The minimal clinically important difference was 2.5 points.
Results: Of the 198 participants randomized, 194 were included in the full analysis set (mean age, 41.3 [SD, 13.6] years; 56.7% were female; and 3.6% were Asian, 7.7% were Black or African American, and 83.0% were White). The dose-response relationship assessed using the MCP-Mod method for change in HAM-A score at week 4 was statistically significant for the 100-μg and the 200-μg dose groups vs placebo (least-squares mean difference, −5.0 points [95% CI, −9.6 to −0.4 points] with 100 μg of MM120 and −6.0 points [95% CI, −9.8 to −2.0 points] with 200 μg of MM120) but the 25-μg and 50-μg dose groups did not reach significance vs placebo (least-squares mean difference, −1.2 points [95% CI, −6.0 to 3.5 points] with 25 μg of MM120 and −1.8 points [95% CI, −7.6 to 4.0 points] with 50 μg of MM120). The adverse events were consistent with the expected effects of MM120. The most common adverse events were visual perceptual changes (illusion, pseudo-hallucination, and visual hallucination), which occurred in 46.2% of participants who received 25 μg of MM120, in 75.0% who received 50 μg, in 92.5% who received 100 μg, in 100% who received 200 μg, and in 10.3% who received placebo; nausea occurred in 7.7%, 27.5%, 40.0%, 60.0%, and 7.7%, respectively; and headache occurred in 12.8%, 22.5%, 35.0%, 27.5%, and 23.1%. Discussion & Conclusions In participants with moderate to severe GAD, a single dose of MM120 produced a dose-dependent reduction in anxiety. These results support the dose-dependent efficacy of MM120 and inform the dose selection for phase 3 pivotal trials.