We licked the frogs so you don’t have to: A comprehensive history and analysis of the chemical syntheses of the classical psychedelics Bufotenin(e) and 5-methoxy-N,N-dimethyltryptamine
Anton A. Homon, Jaxon Laramie, John J. Hayward, John F. Trant
ChemRxiv June 26, 2025 Peer reviewed DOI: 10.26434/chemrxiv-2025-grxh4 via OpenAlex
Summary
Bufotenin and its derivative 5-MeO-DMT are potent psychedelics with potential therapeutic uses, but their research has been limited by regulatory issues and availability. This review compiles all known academic and patent syntheses of bufotenin as of fall 2024, aiming to help researchers find suitable production methods. The authors also discuss challenges that need to be addressed to lower costs for future commercial-scale production.
Study at a glance
| Design | review |
|---|---|
| Key finding | The review collates all existing academic and patent syntheses of bufotenin to assist researchers in identifying appropriate production methods. |
Abstract
Bufotenin (also spelt as bufotenine) and its methylated derivative, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) are potent psychedelics (although the activity of the former is attenuated due to its low propensity to cross the blood-brain-barrier) that are found in many plants but also excreted by specific species of toads. The compounds are regulated differently around the world, and although they have been used in traditional medicine, 20th century prohibition culture has slowed research into their utility for ameliorating psychological disorders and inflammatory & neurodegenerative diseases. However, the global trend towards legalization and a renewed interest in the therapeutic potential of psychedelics has increased the number of clinical and preclinical studies of these and related materials. This necessitates access to large amounts of these compounds, but they are not commercially available on scale. This leaves researchers with a need to either contract for, or make their own, bufotenin. The first synthesis was reported in 1935 by Hoshino and coworkers, and novel syntheses are still being disclosed in the 2020s. This is the first effort to collate and compare all extant academic and patent syntheses (as of fall 2024) into a single review so that researchers can identify the most appropriate route for their own purposes. We conclude by highlighting outstanding challenges that are ripe for solutions to reduce the cost of any future commercial-scale production.