JAMA: Nasal mebufotenin reduced depression symptoms for up to eight weeks

Mebufotenin, also known as 5-MeO-DMT, is a psychedelic substance found in the secretion of the Sonoran Desert toad. The study used a purified synthetic form of the compound rather than the toxin itself.

The phase 2b trial included 193 adults with moderate to severe depression. During their current depressive episode, none had responded to between two and five courses of antidepressant treatment. Participants were randomly assigned to groups receiving 8 mg, 12 mg, or a low comparator dose of 0.3 mg. All participants received psychological support before, during, and after the procedure.

After four weeks, symptoms measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) had decreased by an average of 11.1 points in the 12 mg group, compared with 5.5 points in the low-dose group. In the 8 mg group, the reduction was 12.5 points. The adjusted differences compared with the comparator group were 5.3 and 6.2 points, respectively.

By day 29, 26% of participants in the 8 mg group, 18% in the 12 mg group, and 8% in the 0.3 mg group met the criteria for remission. Thus, a reduction in symptoms should not be equated with recovery in all patients.

Most participants were considered ready to leave the clinic approximately two hours after administration. Adverse events were common, but almost all were mild to moderate. These included headache, nausea, and nasal discomfort; one patient experienced two severe panic attacks.

The authors consider the findings promising, but the drug still requires larger clinical trials. The study evaluated administration under professional supervision with psychological support and does not establish that the substance is safe or effective when used without medical supervision.