Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 15, 2025 Maria Beatriz Bistue Millón, Laura Noguera, Diana Bruno et al. 4 citations
In this first-in-human Phase I clinical trial, a novel sublingual formulation of 5-MeO-DMT was tested at sub-psychedelic doses in adults with moderate to high anxiety and/or depression, but without a formal psychiatric diagnosis or ongoing treatment. The compound was well tolerated across all groups (6 mg, 9 mg, or 12 mg), with no significant adverse events or organ toxicity; mild side effects like nausea and headache were transient. Pharmacokinetics showed rapid absorption, peak plasma concentrations within a median of 20 minutes, and no drug accumulation. Dose-dependent modulation of brain activity occurred without full psychedelic effects, and participants maintained normal daily activities. These results support the safety and feasibility of repeated sub-psychedelic dosing and lay groundwork for future therapeutic trials.