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Bufotenin (5-HO-DMT, N-N-dimethylserotonin, dimethyl serotonin, mappin) is a tryptamine related to the neurotransmitter serotonin. It is an alkaloid found in the skin of toads belonging to the genus Bufo, the seeds belonging to the genus Anadenanthra and some mammals. The drug is linked to hallucinogenic experiences.

The name bufotenin originates from the Bufo genus of toads, which includes several species of toads that release bufotoxin from their paratoid glands. The drug was first isolated from a toad during World War 1 by Austrian chemist Handovsky.

Bufotenin has been used for its hallucinogenic effects where people who have taken the drug orally and intraversouly have experienced perceptual changes. Bufotenin shares a similar structure with other psychedelics, such as psilocin (4-HO-DMT), 5-MeO-DMT and DMT. While Bufotenin has been used recreationally for its psychedelic ability, it has also been used in treatments for patients suffering mental disabilities such as schizophrenia, autism and asymptomatic subjects due to its relationship with serotonin.

History
Bufotenin was first isolated from toad skin, and named by the Austrian chemist Handovsky at the University of Prague during World War I. The structure of bufotenine was first confirmed in 1934 by Heinrich Wieland’s laboratory in Munich, and the first reported synthesis of bufotenine was by Toshio Hoshino and Kenya Shimodaira in 1935. Starting in the 1950’s, Bufotenin became the subject of research, one of the first famous cases was with Fabings and Hawkins who administered different dosages of bufotenin to different inmates in Ohio.

Toads
Bufotenin is a chemical constituent in the venom and eggs of several species of toads belonging to the Bufo genus, but most notably in the Colorado River toad (Bufo alvarius) as it is the only toad species in which bufotenin is present in large enough quantities for a psychoactive effect. Extracts of toad venom, containing bufotenin and other bioactive compounds, have been used in some traditional medicines such as ch’an su (probably derived from Bufo gargarizans), which has been used medicinally for centuries in China.



The toad was "recurrently depicted in Mesoamerican art," which some authors have interpreted as indicating that the effects of ingesting Bufo secretions have been known in Mesoamerica for many years; however, others doubt that this art provides sufficient "ethnohistorical evidence" to support the claim.

In addition to bufotenine, Bufo venoms also contain digoxin-like cardiac glycosides, and ingestion of the venom can be fatal. Ingestion of Bufo toad venom and eggs by humans has resulted in several reported cases of poisoning,  some of which resulted in death.

Contemporary reports indicate that bufotenine-containing toad venom has been used as a street drug; that is, as a supposed aphrodisiac (it is not an aphrodisiac but definitely is a lethal poison ), ingested orally in the form of ch’an su, and as a psychedelic, by smoking or orally ingesting Bufo toad venom or dried Bufo skins. The use of chan'su and love stone (a related toad venom preparation used as an aphrodisiac in the West Indies) has resulted in several cases of poisoning and at least one death. The practice of orally ingesting toad venom has been referred to in popular culture and in the scientific literature as toad licking and has drawn media attention. Albert Most, founder of the Church of the Toad of Light and a proponent of recreational use of Bufo alvarius venom, published a booklet titled Bufo alvarius: The Psychedelic Toad of the Sonoran Desert in 1983 which explained how to extract and smoke the secretions.

Bufotenin is also present in the skin secretion of three arboreal amphibian species of the Osteocephalus genus (Osteocephalus taurinus, Osteocephalus oophagus, and Osteocephalus langsdorfii) from the Amazon and Atlantic rain forests.

Anadenanthera seeds
Bufotenin is a constituent of the seeds of Anadenanthera colubrina and Anadenanthera peregrina trees. Anadenanthera seeds have been used as an ingredient in psychedelic snuff preparations by indigenous cultures of the Caribbean, Central and South America.

Other sources
Bufotenin has been identified as a component in the latex of the takini (Brosimum acutifolium) tree, which is used as a psychedelic by South American shamans, and in the seeds of Mucuna pruriens

Synthesis


One of the ways to synthesize bufotenin is through first treating 5-benzyloxyindole with an oxidizing agent, in the synthesis performed by M.E. Speeter and W.C. Anthony they used oxayl chloride as their oxidizing agent. After oxidizing the reactant, dimethylamine was used, which then produces glyoxlamide. This product can be reduced, in Speeter and Anthony's experiment Lithium aluminum hydride was used, and after treating the reduced product with a catalytic debenzylation it will produce bufotenin.

Uptake and elimination
In rats, subcutaneously administered bufotenin (1–100 μg/kg) distributes mainly to the lungs, heart, and blood, and to a much lesser extent, the brain (hypothalamus, brain stem, striatum, and cerebral cortex) and liver. It reaches peak concentrations at 1 hour and is nearly completely eliminated within 8 hours. In humans, intravenous administration of bufotenin results in excretion of (70%) of injected drug in the form of 5-HIAA, an endogenous metabolite of serotonin, while roughly 4% is eliminated unmetabolized in the urine. Orally administered bufotenine undergoes extensive first-pass metabolism by the enzyme monoamine oxidase.

Mechanism of Action
Bufotenin acts as a serotonin antagonist as it binds to two different receptors, 5-HT2A and 5-HT2C 5-HT2A and 5-HT2C are two receptors that are used activated when using LSD. The 5-HT2A receptor is closely linked to the visual cortex and the orbitofrontal cortex, thus when bufotenin binds to this receptor and creates the perceptual changes in the user. While being an hallucinogenic drug, bufotenin does not share the same strength as 5-MeO-DMT. This is due to bufotenin has a harder time crossing the blood brain barrier. Bufotenin is the most effective when mixed with other halluicongenic drugs, which allows the bufotenin to cross the brain blood barrier much easily.

Lethal dose
The acute toxicity of bufotenin in rodents has been estimated at 200 to 300 mg/kg. Death occurs by respiratory arrest.

Effects in humans

 * All doses were given intravenously unless stated otherwise.

Out of the five experiments, only three of them came to a conclusion. Fabing and Hawkins concluded that the effects of bufotenin was similar to LSD and mescaline but developed and disappeared more quickly, indicating rapid central action and rapid degradation of the drug. Turner and Merlies concluded: "We must reject bufotenine...as capable of producing the acute phase of Cohoba intoxication." Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of Yopo without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered intravenously.

Association with schizophrenia and other mental disorders
A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects; however, subsequent research has failed to confirm these findings.

Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders, such as infant autistic patients. Another study indicated that paranoid violent offenders or those who committed violent behaviour towards family members have higher bufotenin levels in their urine than other violent offenders.

A 2010 study utilized a mass spectrometry approach to detect levels of bufotenin in the urine of individuals with severe autism spectrum disorder (ASD), schizophrenia, and asymptomatic subjects. Their results indicate significantly higher levels of bufotenin in the urine of the ASD and schizophrenic groups when compared to asymptomatic individuals.

Australia
Bufotenin is classified as a Schedule I controlled substance according to the Criminal Code Regulations of the Government of the Commonwealth of Australia.

United Kingdom
In the UK, bufotenin is a Class A drug under the 1971 Misuse of Drugs Act.

United States
Bufotenine (DEA Drug Code 7403) is regulated as a Schedule I drug by the Drug Enforcement Administration at the federal level in the United States and is therefore illegal to buy, possess, and sell.

Pop Culture
In the season eleven episode fifteen of The Simpsons while working as a missionary in the South Pacific, Homer licks a "Bufo" genus toad and experiences some effects from the toad.

In season two episode fourteen of Family Guy, Peter Griffin goes in disguise as a teenager at a local high school to prevent kids from licking toads that contain bufotenin.