Anxiety disorders affect nearly 4% of the world’s population, with generalized anxiety disorder (GAD) being one of the most common and debilitating forms. Despite a range of therapies — from antidepressants to psychotherapy — about half of patients do not achieve meaningful relief. Now, researchers say a novel approach rooted in psychedelics could shift the treatment landscape.
A phase 2b clinical trial has found that MM120, a pharmaceutical form of lysergic acid diethylamide (LSD), produced significant and lasting improvements in people with moderate to severe GAD. Results were published in JAMA, highlighting both the promise and the challenges of developing psychedelic compounds as mainstream therapies.
A long-awaited alternative
Reid Robison, MD, psychiatrist and principal investigator of the trial, emphasized the unmet need: “We haven’t had a new FDA-approved treatment for GAD since 2007. Current medications help some, but too many patients remain stuck with inadequate relief and ongoing side effects.”
Unlike conventional drugs that require daily use, MM120 was tested as a single oral dose. Researchers recruited 198 adults, average age 41, who were randomly assigned to one of four dose levels — 25, 50, 100, or 200 micrograms — or placebo.
The standout results came from the 100-microgram group, which showed a 7.6-point greater reduction on the Hamilton Anxiety Rating Scale compared to placebo. More than 65% of these participants experienced meaningful improvement, and nearly half achieved full remission by week 12.
“The rapid and durable response we observed is unlike what we typically see with current first-line therapies,” Robison noted.
How it works
MM120 appears to drive its effect through neuroplasticity — a temporary period during which the brain becomes more flexible and capable of rewiring. Participants described their sessions as deeply meaningful, which Robison believes may play a role alongside the measurable biological changes.
“Profound experiences contribute to the initial shift,” he explained, “but the brain’s openness to change may help solidify and sustain those improvements.”
Interestingly, while many participants guessed they had received the active drug, only those on higher doses showed clinically significant benefits — evidence, the researchers argue, that the improvements were not simply placebo-driven.
Broader impact on mood
The trial also found improvements in depression scores, reflecting the frequent overlap between anxiety and depressive disorders. “Given how intertwined these conditions are, the potential dual benefit is encouraging,” Robison said.
Expert caution
Outside experts praised the innovation but warned against premature conclusions. Greg Fonzo, PhD, co-director of the Center for Psychedelic Research & Therapy at UT Austin, described the findings as “very promising,” particularly given the durability of effect from a single dose. Still, he emphasized the need for larger, more diverse trials and long-term follow-up to assess safety and relapse rates.
Others, like Stacy Doumas, MD, chair of psychiatry at Hackensack Meridian Jersey Shore University Medical Center, urged caution. “Treating anxiety with a substance historically linked to psychosis feels counterintuitive. The risks — including rare but serious adverse effects — demand careful oversight,” she said.
The road ahead
MindMed, the company developing MM120, has already moved into phase 3 trials. These larger studies will help determine whether the drug is safe and effective enough for FDA approval.
For millions living with GAD, the trial offers a glimpse of what could be a transformative option — though experts stress the journey from lab to clinic is far from over.
“Exploring psychedelics for psychiatric medicine is no longer fringe,” Robison said. “But scientific rigor and patient safety must guide every step.”
