LSD for Generalized Anxiety Disorder: New Findings Review With Maurizio Fava, MD

Maurizio Fava, MD, discussed recent findings from a phase 2 randomized clinical trial evaluating lysergic acid diethylamide (LSD) for generalized anxiety disorder (GAD). The study found that a single administration of higher-dose LSD produced robust and sustained reductions in anxiety symptoms lasting up to 12 weeks, suggesting that dosing every few months could offer durable benefit in a typically chronic condition.1 LSD was well tolerated by patients in the study, though acute psychedelic effects required observation on the day of administration. Notably, no psychotherapy was administered, providing evidence that LSD may exert therapeutic effects independent of adjunctive psychotherapeutic support.

Fava also addressed concerns regarding functional unblinding, a common critique of methods in psychedelic research. Although participants receiving the second-lowest LSD dose experienced psychedelic effects similar to higher doses, only the 2 highest doses yielded significant clinical improvement, indicating that the observed efficacy was unlikely to be an artifact of expectancy bias.

He compared this approach with current GAD treatments, such as selective serotonin reuptake inhibitors, which require daily dosing and cause persistent adverse effects like sexual dysfunction.2 In contrast, a single LSD administration may produce transient side effects but long-term benefit for a profile potentially more acceptable to patients.

Fava emphasized the need for phase 3 replication studies in larger populations to confirm efficacy and safety of LSD to treat GAD. He also encouraged clinicians to move beyond the stigma surrounding psychedelic agents, recognizing their growing evidence base and therapeutic potential in anxiety disorders.

Dr Fava is psychiatrist-in-chief of the Department of Psychiatry at Massachusetts General Brigham Academic Medical Center.

References

1. Robison R, Barrow R, Conant C, et al. Single treatment with MM120 (lysergide) in generalized anxiety disorder: a randomized clinical trial. JAMA. Published online September 4, 2025.

2. Edinoff AN, Akuly HA, Hanna TA, et al. Selective serotonin reuptake inhibitors and adverse effects: a narrative review. Neurol Int. 2021;13(3):387-401.