UCSF researcher Jennifer Mitchell in a lab examining MM120, an LSD-based drug for treating generalized anxiety disorder.

UCSF researchers test LSD-based MM120 for generalized anxiety disorder

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UCSF neuroscientist Jennifer Mitchell and collaborators are evaluating MM120, a pharmaceutical form of LSD, as a potential treatment for generalized anxiety disorder. A randomized clinical trial published in JAMA found that a single dose reduced anxiety symptoms versus placebo, with benefits persisting up to 12 weeks in the optimal dose group, according to the study and the drug’s sponsor.

Generalized anxiety disorder (GAD) affects millions of Americans and can impair daily functioning at work, home and in relationships. U.S. federal data estimate that about 2.7% of adults experience GAD in a given year and 5.7% do so at some point in their lives. Common symptoms include persistent worry, difficulty concentrating, sleep problems, fatigue and muscle tension. (nimh.nih.gov)

At UC San Francisco, neuroscientist Jennifer Mitchell is among the researchers studying MM120, a controlled pharmaceutical formulation of lysergide (LSD). UCSF’s coverage describes the approach as aiming to promote neuroplasticity and more flexible communication among brain regions—hypotheses for how psychedelics might disrupt rigid thought patterns seen in anxiety disorders. (sciencedaily.com)

Evidence to date comes from a phase 2b, multicenter, randomized, double‑blind, placebo‑controlled trial published September 4, 2025, in JAMA. The study enrolled 198 adults with moderate‑to‑severe GAD who received a single dose of MM120 (25, 50, 100 or 200 micrograms) or placebo. At the primary week‑4 endpoint, the 100‑µg and 200‑µg doses reduced Hamilton Anxiety Rating Scale (HAM‑A) scores by about 5.0 and 6.0 points more than placebo, respectively; the trial prespecified a minimal clinically important difference of 2.5 points. (dx.doi.org)

Benefits appeared to persist beyond the primary endpoint. According to MindMed, the drug’s sponsor, the 100‑µg group maintained improvements through week 12 with a 7.7‑point advantage over placebo and achieved response and remission rates of 65% and 48%, respectively; independent news coverage has reported similar durability. These longer‑term figures come from the company’s analyses and meeting presentations rather than the JAMA primary endpoint. (ir.mindmed.co)

Side effects in the JAMA trial were generally transient and dose‑related. Visual perceptual changes (including illusions and hallucinations), nausea and headache were the most common adverse events and increased with higher doses. Based on the balance of efficacy and tolerability, 100 µg was identified for advancement to pivotal trials. (dx.doi.org)

For context, first‑line drugs for GAD such as selective serotonin reuptake inhibitors typically outperform placebo on the HAM‑A by roughly 2–3 points on average across trials, according to a network meta‑analysis—smaller mean differences than those reported at week 4 for the optimal MM120 dose in the JAMA study. Direct head‑to‑head comparisons with MM120 have not been conducted. (pubmed.ncbi.nlm.nih.gov)

MindMed has since begun phase 3 development of MM120 in GAD, including a U.S. study initiated in late 2024. As research proceeds, Mitchell and UCSF note that trial participants are closely monitored in clinical settings; UCSF also describes practical steps used in its program to mitigate nausea and support participation, such as light meals, prophylactic anti‑nausea medication and careful screening by experienced clinicians. (ir.mindmed.co)

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