Bufotenin

Bufotenin (also spelled bufotenine) is a psychoactive alkaloid found in a variety of organisms, including certain toads, mushrooms, and plants. It is related to tryptamine¹ (as N,N-dimethyl-5-hydroxytryptamine) and serotonin² (as N,N-dimethylserotonin).

Bufotenin first appeared in the chemical literature in the 1920s, when Japanese researcher Kansho Ryo isolated it from toad venom and described its pharmacology. It was studied extensively in the 1930s by Heinrich Wieland³ and co-workers at the University of Munich, who isolated it from the venom of toads of the genus Bufo, for which the compound is named. Both authors cited an Austrian chemist named Handovsky who had discovered bufotenin in toad skin in the 1910s.

In 1953, Wieland went on to identify bufotenin in the yellow fungus Amanita mappa. He noted that the compound, previously called mappine, was identical to bufotenin. Other early researchers into toad venoms, including bufotenin, were Ko Kuei Chen, a Chinese–American pharmacologist at Eli Lilly (Indianapolis) and Verner L. Stromberg at the National Institutes of Health (Bethesda, MD), who in 1954 isolated it from the seeds of Piptadenia peregrina (now Anadenanthera peregrina), a Caribbean shrub known to indigenous peoples as cohoba.

The first synthesis of bufotenin is attributed to Toshio Hoshino and Kenya Shimodaira, who worked with Wieland at Munich. In 1954, John Harley-Mason* and A. H. Jackson at Cambridge University (UK) published an improved six-step synthesis starting with 2,5-dimethoxybenzaldehyde.

From the time of its discovery, bufotenin has been known for its hallucinogenic effects. In 2014, F. J. Carod-Artal at Hospital Virgen de la Luz (Cuenca, Spain) wrote that pre-Columbian Mesoamerican cultures used skins or extracts of Bufo toads to induce trance states in ritual settings and to enhance the effects of alcoholic drinks. In 1956, Physicians Howard D. Fabing* and J. Robert Hawkins at Christ Hospital (Cincinnati) described several responses from injecting bufotenin into humans that ranged from purpling of the skin to tightening of the throat and chest to visualizing colored spots in the subject’s surroundings.

Subsequent studies reported similar ranges of psychological effects. In a nearly disastrous 1959 experiment, physicians William J. Turner and Sidney Merlis of Central Islip, NY, injected a bufotenin solution into schizophrenic patients. Instead of helping the patients or even producing hallucinogenic effects, the compound produced near-fatal results.

For additional reading about bufotenin, see the ScienceDirect information page.

1. CAS Reg. No. 61-54-1.
2. CAS Reg. No. 50-67-9.
3. Wieland was awarded the 1927 Nobel Prize in Chemistry for his work on bile acids.