Can Psychedelics Treat TRD?

Background: Treatment-resistant depression (TRD) has been defined as failing at least 2 adequate trials of antidepressants. There are no U.S. Food and Drug Administration–approved medications for TRD. There has been an increase in investigating psychedelics for the treatment of depression and other psychiatric disorders. This article focuses on inhaled mebufotenin (GH001), which is a rapid-acting, nonselective serotonin agonist (5-HT 1A ). This psychoactive agent can be found in plants and a toad native to Colorado. Early phase trials of this agent have demonstrated tolerability in healthy individuals. Objective: To evaluate the efficacy, safety, and tolerability of mebufotenin compared to placebo in individuals with TRD. Design: Double-blinded, placebo-controlled, randomized clinical trial. Participants: 81 adult participants with TRD in Europe. Methods: The trial was conducted from May 2023 to March 2025 at multiple sites in Europe. Individuals had to meet the definition of T more...