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.
ChemRxiv
November 26, 2025
Anton A. Homon, P. V. Vara Prasad, Elham Pourian et al.
A streamlined, chromatography-free synthesis of 5-MeO-DMT from melatonin achieves 76% overall yield, producing 64 g of analytically pure product in under 5 days. Demethylation of 5-MeO-DMT yields bufotenin hydrobromide in 51% yield (22 g) within an additional 2 days. Candidate prodrugs of bufotenin are prepared to potentially improve nanoformulation and blood-brain-barrier passive uptake. The method uses inexpensive, widely available melatonin, avoiding expensive starting materials, extensive chromatography, and late-stage chemistries that raise toxicity concerns.
Advanced Therapeutics
October 5, 2025
William Charles Hosie, Abhinandan Banerjee, Mary A. Egbuta et al.
A new type of biocompatible emulsifier was created by chemically linking hemp protein with green tea polyphenols. These emulsifiers were used to produce nanoemulsions of hemp oil containing the sensitive drug 5-MeO-DMT, with droplets around 200 nanometers and stable surface charge. The polyphenols retained their antioxidant activity, protecting the drug from oxidative stress. The emulsions remained stable for four weeks without separating. Cellular imaging showed the formulation was taken up by cells, and toxicity tests indicated acceptable cell viability. This nanodelivery platform offers a way to improve the bioavailability and dosing consistency of 5-MeO-DMT.
ChemRxiv
June 26, 2025
Anton A. Homon, Jaxon Laramie, John J. Hayward et al.
Bufotenin and 5-MeO-DMT are potent psychedelics found in plants and toad secretions, but their therapeutic potential for psychological disorders and inflammatory or neurodegenerative diseases has been hindered by prohibition and limited commercial availability. This review collates all known academic and patent syntheses of bufotenin from 1935 to 2024, comparing routes to help researchers choose the most suitable method. The authors highlight challenges that need solving to reduce costs for future commercial-scale production, aiming to support the growing clinical and preclinical research into these compounds.
ChemRxiv
February 27, 2025
William Charles Hosie, Mary Augustina Egbuta, Kasra Razmkhah et al.
A new class of biocompatible emulsifiers was created by conjugating hemp protein with green tea polyphenols using a simple pH-assisted coupling protocol. These emulsifiers were used to produce hemp oil nanoemulsions enriched with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), achieving average droplet sizes of about 200 nm and ζ potential values of about -40 mV. The polyphenol-conjugated emulsifiers protected the sensitive drug under simulated oxidative stress, indicating retained antioxidant properties. The emulsions resisted various stressors and showed colloidal stability for 4 weeks without phase separation. Cellular uptake was confirmed by imaging, and in vitro cytotoxicity assays showed acceptable cell viability with drug-loaded nanoemulsions, offering an ingestible formulation for improved bioavailability of 5-MeO-DMT.