Single Dose of MM120 (LSD) Shows Lasting Anxiety Reduction in GAD: Phase 2b Results

A single 100 μg dose of MM120 (lysergide D-tartrate, LSD) significantly reduced anxiety symptoms in adults with generalized anxiety disorder (GAD), with improvements sustained through 12 weeks, according to the first randomized, placebo-controlled trial of its kind published today in JAMA.¹

“This study is a true turning point in the field of psychiatry,” investigator Maurizio Fava, MD, member of the MindMed Scientific Advisory Board and chair of Mass General Brigham Department of Psychiatry, said in a statement.² “For the first time, LSD has been studied with modern scientific rigor, and the results are both clinically meaningful and potentially paradigm-shifting for the treatment of GAD.”

Despite 26 million adults in the US diagnosed with GAD, the US Food & Drug Administration (FDA) has not approved a new medication for this indication since 2007.² However, 50% of patients fail first-line GAD treatments.

“I have seen firsthand the devastating toll GAD takes on patients and their families, which is why it is so significant that a single dose of MM120 delivered rapid, robust, and lasting effects,” Fava continued.² “These results highlight the promise of psychedelics in psychiatric medicine.”

MindMed conducted MMED008, a multicenter, randomized, placebo-blind, phase 2b study evaluating a single administration of MM120 at 4 dose levels (25 [n = 39], 50 [n = 40], 100 [n = 40], or 200 [n = 40]) μg as monotherapy, without any psychotherapeutic intervention, in adults with moderate to severe GAD.¹ The sample included 198 adults aged 18 – 74 years (mean age, 41.3 years), with 56.7% female and 83% White (7.7% Black or African American and 3.6% Asian). The dose-response relationship was evaluated using the multiple comparison procedure modeling (MCP-Mod) method for change in Hamilton Anxiety Rating Scale at week 4.

The study met its primary endpoint, with MM120 demonstrating a dose-response relationship at week 4 with the 100 μg (least-squares mean difference, −5.0 points; 95% confidence interval [CI], −9.6 to −0.4 points) and the 200-μg (−6.0 points; 95% CI, −9.8 to −2.0 points) dose groups vs placebo. The study found no significant difference between the 25 μg (least-squares mean difference, −1.2 points; 95% CI, −6.0 to 3.5 points) and 50 μg (−1.8points; 95% CI, −7.6 to 4.0 points) doses compared with placebo.¹

The trial also met its key secondary endpoint, demonstrating a significant symptom improvement versus placebo on the Hamilton Anxiety Rating Scale (HAM-A). The analysis showed that 100 μg was the optimal dose of MM120. At week 4, this dose achieved a 7.6-point greater reduction in HAM-A scores compared to placebo (-21.3 vs. -13.7; P <.0004). Participants on MM120 100 μg had a 65% clinical response rate and a 48% clinical remission rate sustained to week 12.¹

This study also met other secondary outcomes, including clinician-rated disease severity measured by the Clinical Global Impression-Severity (CGI-S) scale, changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), and measures of functional disability and quality of life.

On average, CGI-S scores improved from 4.8 to 2.2 in the 100 μg dose group, reflecting a 2-category shift from “markedly ill” to “borderline ill” at week 12. This was compared to a 4.9 to 3.5 improvement in the placebo group (P =.003).¹

Furthermore, MM120 showed rapid clinical activity, working as early as day 2 and sustained through week 4 and 12. MM120 100 μg also led to significant MADRS improvement vs placebo, with a difference of 5.7 points at week 4 (P ≤.05) and a difference of 6.4 points at week 12 (P ≤.05).¹

The safety profile of MM120 was comparable to previous findings, with mild-to-moderate adverse events occurring on dosing day. Common adverse events included visual perceptual changes, including illusion, pseudo-hallucination, and visual hallucination.¹ These visual perceptual changes occurred in 46.2% of participants who received 25 μg of MM120, 75% who received 50 μg, 92.5% who received 100 μg, 100% who received 200 μg, and 10.3% who received a placebo.

Another common adverse event included nausea, occurring in 7.7% receiving 25 μg, 27.5% receiving 50 μg, 40% receiving 100 μg, 60% receiving 200 μg, and 7.7% receiving placebo.¹ Headaches occurred in 12.8%, 22.5%, 35.0%,27.5%, and 23.1% of participants, respectively.

The dose-response results inform MindMed’s ongoing phase 3 trial focusing on the MM120 Orally Disintegrating Tablet (ODT). Topline results for MindMed’s Voyage trial, evaluating the efficacy, durability, and safety of MM120 ODT for GAD, are expected in the first half of 2026.²

“Our Phase 2b results—marking the first well-controlled clinical study to evaluate dose-response relationships of LSD in a psychiatric population—demonstrate the meaningful impact of a single 100 μg dose of MM120 in significantly reducing anxiety symptoms,” said Daniel Karlin, MD, chief medical officer of MindMed.²

References

1. Robison R, Barrow R, Conant C, et al. Single Treatment with MM120 (Lysergide) in Generalized Anxiety Disorder. JAMA.doi:10.1001/jama.2025.13481. Published online September 4, 2025.

2. Journal of the American Medical Association (JAMA) Publishes Results from First-Ever Randomized, Placebo-Controlled Clinical Trial Assessing the Dose-Dependent of MM120 (Lysergide D-Tartrate, LSD) in Generalized Anxiety Disorder (GAD). MindMed. Assessed September 4, 2025.