What is bufotenin? The 5-hydroxy cousin of DMT and psilocin, explained

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Bufotenin is one of the most argued-about molecules in the tryptamine family. It shares a skeleton with DMT, serotonin and psilocin, it has turned up in ancient snuff tubes and in toad secretions, and for decades researchers looked for it in the urine of psychiatric patients. This article explains what it is, what is and isn’t known about its effects, and where it stands in law. For the parent molecule, start with our pillar, what is DMT.

What is bufotenin?

Chemically, bufotenin is a tertiary amine made of N,N-dimethyltryptamine bearing an extra hydroxy (–OH) group at position 5 of the indole ring, the two-ring core shared by all tryptamines (PubChem, bufotenine). Its formula is C12H16N2O and its systematic name is 3-[2-(dimethylamino)ethyl]-1H-indol-5-ol. Other names in official listings include 5-hydroxy-N,N-dimethyltryptamine, N,N-dimethylserotonin and mappine (eCFR, 21 CFR 1308.11). Both spellings, bufotenin and bufotenine, are used in the scientific literature. Evidence: established.

Its name points to *Bufo*, the toad genus whose skin and glands contain it. A 1996 review of the toad’s history and chemistry says bufotenine has been at the centre of a scientific debate since its discovery in 1893 (Lyttle et al., 1996). In 1961 Julius Axelrod reported an enzyme, found mainly in rabbit lung, that adds methyl groups to serotonin and tryptamine to make bufotenine and DMT, which he called “psychotomimetic metabolites” (Axelrod, 1961). That enzyme is now known as INMT. Evidence: established.

How is bufotenin related to DMT, serotonin and psilocin?

Think of DMT as the base shape. Add a hydroxyl at position 5 and you get bufotenin. Serotonin, the body’s own messenger, also has that 5-hydroxyl, but carries no methyl groups on its nitrogen, so bufotenin is serotonin with two methyls added. Put the hydroxyl at position 4 instead and you get psilocin; PubChem lists psilocin and bufotenin with the identical formula C12H16N2O, differing only in the ring position: 1H-indol-4-ol versus 1H-indol-5-ol (PubChem, psilocin; PubChem, serotonin; PubChem, DMT). Molecules like this are called positional isomers. Our guide to DMT’s chemical structure draws the whole family. Evidence: established.

Because the two isomers weigh the same, forensic labs have to prove which one they have. A 2020 study from Israel’s police forensic laboratory made all four ring isomers (4-, 5-, 6- and 7-hydroxy-DMT) and showed routine methods can tell them apart, so a suspected mushroom sample can be confirmed as psilocin with bufotenin ruled out (Mishraki-Berkowitz et al., 2020). That answers a common search: magic mushrooms are known for psilocybin and psilocin, not bufotenin. See is there DMT in magic mushrooms? and psilocin vs psilocybin. Evidence: established.

Bufotenin vs 5-MeO-DMT

5-MeO-DMT differs from bufotenin by one methyl group: a methoxy (–OCH3) where bufotenin has a hydroxyl. PubChem’s record for 5-MeO-DMT even lists it under the title O-methylbufotenine (PubChem, 5-MeO-DMT). The link is also metabolic: in the body, the liver enzyme CYP2D6 removes that methyl from 5-MeO-DMT to produce bufotenine as an active metabolite, which binds the 5-HT2A receptor more strongly than its parent (Reckweg et al., 2022). For the 5-MeO-DMT and DMT comparison itself, read 5-MeO-DMT vs DMT. Evidence: established.

Is bufotenin psychedelic in humans?

Nobody has settled it. At the receptor level, a 2000 review summarised experiments showing bufotenine acts like LSD, psilocin and 5-MeO-DMT at the 5-HT2A and 5-HT2C receptors linked to psychedelic effects. The author argued that the reported lack of classic effects in human experiments is best explained by bufotenine’s poor ability to cross the blood–brain barrier, the filter between the bloodstream and the brain, rather than by a lack of receptor activity, while stating that direct human evidence of hallucinogenic activity “seems lacking” (McBride, 2000). Evidence: unresolved.

The human record is thin and conflicting. In 1956, Howard Fabing and J. Robert Hawkins published a short report in Science on intravenous bufotenine injections in people (Fabing and Hawkins, 1956). A later review notes that these first reports of hallucinogenic activity were not replicated in a 1959 study by Turner and Merlis, and that bufotenine’s status as a hallucinogen “has remained a matter of controversy” (Winter et al., 2011). In 1985, a single medically trained volunteer given bufotenine intravenously had profound but short perceptual and emotional changes, and the compound left the blood quickly (McLeod and Sitaram, 1985). Doses are not reproduced here. Evidence: unresolved.

In 2001, the ethnobotanist Jonathan Ott published a series of uncontrolled self-experiments in which he concluded that bufotenine’s visionary activity “has been established” (Ott, 2001). One author testing on himself, with no blinding or placebo, is a report, not proof. Animal work leans the other way: mice trained to recognise 5-MeO-DMT did not treat bufotenine as similar, while a more fat-soluble version of it gave an intermediate response, consistent with the brain-entry explanation (Winter et al., 2011). Evidence: unresolved (self-report and animal data).

Its effects outside the brain are better documented. In a 2023 lab study, bufotenin increased the force of contraction of human heart-muscle tissue from the atrium through the serotonin 5-HT4 receptor, and did the same in mouse hearts engineered to carry that human receptor (Neumann et al., 2023). That was tissue in a dish, not people, but it is one reason researchers describe bufotenin as active on the body as well as being debated as a psychedelic. Evidence: preliminary.

Where does bufotenin appear in archaeology?

Mostly in South American snuff equipment. At Chavín de Huántar in Peru, chemical analysis of 23 artifacts, mostly bone tubes, from a sealed underground gallery found traces of bufotenine in four of them, alongside nicotine and, in one, DMT; the researchers treat bufotenine and DMT as molecular markers of vilca (*Anadenanthera*), and also found its microscopic plant remains (Rick et al., 2025). An earlier landmark was Torres and colleagues’ 1991 chemical and contextual analysis of snuff powders from pre-Hispanic San Pedro de Atacama in Chile (Torres et al., 1991). Our ancient DMT snuffs article covers these finds and their limits in depth. Evidence: established for the detections.

A residue shows which molecules touched an object, not who used it, how, or what they experienced, so these finds say nothing by themselves about bufotenin’s effects. Evidence: established as a limit of residue chemistry.

What is the bufotenin toad connection?

Two toads are usually meant. The Sonoran Desert toad, *Incilius alvarius*, secretes mainly 5-MeO-DMT, together with bufotenine (Reckweg et al., 2022); our Bufo alvarius article covers its biology, conservation and the “toad licking” myth. The cane toad, *Rhinella marina* (formerly *Bufo marinus*), is mainly a poisoning risk: oral exposure to its secretions can be fatal to dogs without early treatment, with drooling, gut, breathing and nerve signs and sometimes severe heart rhythm problems (Johnnides et al., 2016). Evidence: established.

Is bufotenine found in the human body?

Yes, in small amounts. A 2005 Finnish study using sensitive mass spectrometry notes that, in mammals, endogenous bufotenine and DMT had been identified only in human urine. It found large amounts of bufotenine in stools, only small amounts in body or nerve tissue, and none in blood. The authors suggest that urinary and faecal bufotenine come from cells of the kidney and gut, without ruling out gut bacteria (Kärkkäinen et al., 2005). Evidence: established for the detections; preliminary for where it comes from. For DMT itself, see does the brain make DMT?.

The old schizophrenia hypothesis

Axelrod’s 1961 finding fed the transmethylation hypothesis: the idea that the body might make psychosis-like compounds from its own serotonin. The same year, a paper reported “a bufotenin-like substance in the urine of schizophrenics” (Fischer et al., 1961). In 1995 a Japanese team detected urinary bufotenine in 13 of 15 people with schizophrenia, 15 of 18 with depression and most autistic patients tested, but in only 2 of 200 healthy controls (Takeda et al., 1995). Evidence: preliminary (small, older studies).

A 2025 systematic review pooled eight studies. Bufotenine was detected in the urine of 226 of 275 patients with a mental illness (82%) and 92 of 318 controls (29%), but the results were heterogeneous: one study found none in anyone, and two found large overlap between groups. The author concludes it is too early to propose bufotenine as a biomarker (Clarke, 2025). Finding a molecule in urine does not show that it causes symptoms. Evidence: unresolved.

Is bufotenin legal in Canada and the US?

In Canada, it is not named. We read Schedule III of the Controlled Drugs and Substances Act on 21 October 2026, in the consolidation current to 30 September 2026. Item 7 reads “N,N–Dimethyltryptamine (DMT) (3–[(2–dimethylamino) ethyl]indole) and any salt thereof”, and items 11 and 12 list psilocin and psilocybin, but bufotenine does not appear anywhere in the Act’s text (Justice Laws, CDSA). Not named does not mean legal to sell or safe, and laws change. In the United States, federal regulations list bufotenine in Schedule I, item (d)(17), DEA code 7433 (eCFR, 21 CFR 1308.11). See is DMT legal in Canada. This is not legal advice. Evidence: established for what the texts say.

What we still don’t know

• Whether bufotenin is psychedelic in people at all. Human data are a few old, small or uncontrolled reports that disagree (unresolved).
• How much of it reaches the human brain, the core of the blood–brain barrier explanation (unresolved).
• Whether the body’s own bufotenine has any job, or any link to mental illness. Urine studies conflict (unresolved).
• Where the bufotenine in human urine and stools comes from: our own cells or gut bacteria (preliminary).
• How ancient snuff users experienced preparations that contained it. Residues cannot tell us (unresolved).

The fair summary: bufotenin is a well-characterised molecule, a positional isomer of psilocin and a close relative of DMT, serotonin and 5-MeO-DMT, with a long and argumentative research history. Its chemistry is established; its effects on the human mind are not. For how DMT itself turns up in living things, read where does DMT come from in nature?. Evidence: established for the chemistry, unresolved for the psychoactivity.

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