Topic starter
There is a new scientific article that investigates whether a single treatment with MM120, a clinical formulation of lysergide, can reduce anxiety symptoms in people with generalized anxiety disorder.
In it, we discuss:
The researchers conducted a phase 2b, multicenter, randomized, double-blind, placebo-controlled study in adults with moderate to severe generalized anxiety. A total of 198 participants were randomized at 22 psychiatric research centers in the United States. They received a single dose of placebo or 25, 50, 100, or 200 micrograms of MM120.
The real focus of this article lies on the dose-response relationship. The authors primarily wanted to know which dose has the clearest effect on anxiety symptoms, measured with the Hamilton Anxiety Rating Scale after four weeks. This is relevant because a single psychedelic treatment could potentially have a longer-lasting effect than classic daily anxiety medication.
The results show that the higher dosages were particularly effective. After four weeks, the 100 microgram and 200 microgram groups showed a statistically significant decrease in anxiety compared to placebo. The difference on the HAM-A was 5.0 points in favor of 100 microgram and 6.0 points in favor of 200 microgram. The lower dosages of 25 and 50 microgram did not reach statistical significance.
Additional reporting on this study also indicates that the 100 microgram dose is likely the most clinically attractive. That dose showed rapid and sustained effects, with response and remission rates remaining visible until week 12. Thus, 100 micrograms appears to offer a better balance between efficacy and tolerability than 200 micrograms.
The side effects were consistent with the expected acute effects of lysergide. Visual perception changes were dose-dependent and were observed in 46.2 percent of the 25 microgram group, 75.0 percent of the 50 microgram group, 92.5 percent of the 100 microgram group, and 100 percent of the 200 microgram group, compared to 10.3 percent in the placebo group. Nausea and headache also occurred frequently, particularly at the higher doses.
It is important to note, however, that this study did not test a classic psychotherapy session with extensive supervision, but rather a single-administration pharmacological intervention within a strict research protocol. Additionally, blinding remains difficult in psychedelic studies because participants often notice whether they have received an active substance.
In one sentence: this article shows that a single treatment with MM120 can reduce dose-dependent anxiety in generalized anxiety disorder, with 100 and 200 micrograms proving particularly effective and 100 micrograms likely providing the best balance.
Spoiler
New article description
Abstract
Importance: Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed.
Objective: To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD.
Design, settings, and participants: 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.
Interventions: 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) or MM120 or placebo (n = 39).
Main outcome and measures: 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%.
Conclusions and relevance: 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.
Keywords: LSD; lysergide; generalized anxiety disorder; GAD; MM120; anxiety; randomized clinical trial; placebo-controlled trial; HAM-A.
Posted : 18 March 2026 14:57