Single-dose LSD formulation lowers anxiety in early trial but raises safety and regulatory questions

A randomized clinical trial published in the Journal of the American Medical Association found that a single oral dose of MM120, a pharmaceutical formulation of lysergic acid diethylamide (LSD), produced significant reductions in anxiety symptoms among adults with moderate to severe generalized anxiety disorder (GAD), with the largest effects at a 100‑microgram dose.

The multicenter study, led by Daniel Karlin, M.D., chief medical officer of MindMed, enrolled nearly 200 adults ages 18 to 74 who were randomly assigned to receive a single oral dose of MM120 at one of four dose levels (25, 50, 100 or 200 micrograms) or a matching placebo. Participants were observed in private rooms with two trained monitors for at least 12 hours after dosing; no psychotherapy was provided. Anxiety symptoms were assessed at one, two, four, eight and 12 weeks, with the four‑week evaluation set as the primary endpoint.

At the primary four‑week time point, patients who received the highest doses had significantly lower anxiety scores than those who received placebo. The trial reported dose‑dependent effects, with the 100‑microgram level showing the most consistent benefit; investigators said the 200‑microgram dose also outperformed placebo. Lower doses (25 and 50 micrograms) did not show significant improvement compared with placebo. By 12 weeks, 65 percent of patients who received 100 micrograms showed clinical benefit and nearly half were in remission from anxiety.

Investigators also measured depressive symptoms and found significant improvements linked to the higher LSD doses. Karlin described the onset of effect as rapid. The trial's safety assessments identified common acute side effects that included hallucinations, nausea and headache.

The study team highlighted several limitations. Karlin and colleagues noted the potential for "functional unblinding," in which participants correctly guessed whether they had received active medication because of the drug's perceptual effects, potentially biasing subjective outcome reports. The trial did not include adjunctive psychotherapy, so the results reflect MM120 as a monotherapy after a single supervised administration rather than as part of a psychotherapeutic protocol used in some other psychedelic studies.

Regulatory and safety considerations remain prominent. LSD is classified as a Schedule I substance by the U.S. Drug Enforcement Administration, a category that denotes high potential for abuse and no accepted medical use; Schedule I drugs are restricted to approved research uses and are not legally prescribed for treatment. MindMed said it plans two larger, late‑stage trials to follow participants for a longer period and, if those studies confirm efficacy and safety, to seek Food and Drug Administration approval for MM120.

Experts who follow psychedelic research urged careful oversight. Fox News senior medical analyst Dr. Marc Siegel noted that the FDA has in recent years designated psychedelics such as LSD, psilocybin and MDMA as potential breakthrough therapies, and he emphasized the need for meticulous monitoring of side effects and effectiveness. Siegel and other clinicians have warned that psychedelics can cause acute hallucinations and have been associated with paranoia, mood swings, elevated heart rate and, in rare cases, prolonged psychosis.

Hadas Alterman, a Washington, D.C., attorney who specializes in psychedelic medicine, said the current resurgence of clinical research reflects changing regulatory attitudes rather than a purely cultural trend. She pointed to the 1962 Kefauver–Harris amendments, which expanded FDA authority and required robust evidence from controlled trials for drug approval, and said the excess recreational use of psychedelics in the 1960s contributed to a decades‑long pause in clinical investigation.

Policymakers have recently signaled interest in exploring psychedelic therapies. Health and Human Services Secretary Robert F. Kennedy Jr. and Department of Veterans Affairs Secretary Doug Collins have expressed support for research into these agents; Kennedy told members of Congress that therapeutic use in clinical settings is a priority and suggested progress could occur within a year, according to news reports.

Clinicians and researchers stressed that these findings do not change the current legal status of LSD and urged that further study is required to define long‑term safety, optimal dosing, the role of psychotherapy, and which patients may benefit or be harmed. The JAMA publication represents an early, randomized evaluation of MM120 monotherapy in GAD and sets the stage for larger trials to confirm whether a regulated, pharmaceutical formulation of LSD can be an approved treatment option.