We Licked the Toads so You Don’t Have to: A Comprehensive Analysis of the Chemical Syntheses of the Classical Psychedelics Bufotenin(e) and 5‐Methoxy‐ N , N ‐Dimethyltryptamine
ChemMedChem February 25, 2026 Anton A. Homon, Jaxon Laramie, John J. Hayward et al.
Bufotenin and 5-MeO-DMT are potent psychedelics found in plants and toad secretions. Although used in traditional medicine, 20th-century prohibition slowed research into their therapeutic potential for psychological disorders and inflammatory and neurodegenerative diseases. Recent global trends toward legalization have increased clinical and preclinical studies, creating demand for large amounts of these compounds that are not commercially available on scale. The first bufotenin synthesis was reported in 1935, and new syntheses continue to appear in the 2020s. This review collates and compares all extant academic and patent syntheses as of fall 2024, enabling researchers to identify the most appropriate route. Outstanding challenges for reducing commercial-scale production costs are highlighted.