RESEARCH MONOGRAPH · KDC-MN-342

Bufotenin

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

44/100

Tryptamine with weird PK and a thin clinical evidence base, mostly historical pharmacological interest

Bufotenin (5-hydroxy-N,N-dimethyltryptamine) is the hydroxylated tryptamine analog of N,N-DMT that occurs in Anadenanthera seeds and some toad-skin secretions. It was historically used in South American snuffs (yopo, cohoba) and has a strange pharmacological profile that we honestly find more curious than convincing.

Mechanism: 5-HT2A agonist similar to DMT but with poor blood-brain barrier penetration because of the hydroxyl group (the phenol is ionized at physiological pH and crosses lipid membranes much less efficiently than the methoxy or unsubstituted equivalents). 5-MeO-DMT is the methylated version of bufotenin and crosses the BBB much better. So bufotenin produces a lot of peripheral pharmacology (cardiovascular, GI) at doses where the central effects are still developing.

The historical use as a snuff bypasses some of the BBB issue by giving fast nasal-mucosal absorption with rapid CNS entry before peripheral metabolism dominates, which is why yopo and cohoba preparations produced central effects in traditional contexts that oral or injected bufotenin in clinical research often hasnt replicated convincingly. Fabing and Hawkins ran some of the early clinical studies in the 50s with IV bufotenin and the reports were mostly of intense unpleasant peripheral effects with relatively modest psychedelic activity. Strassman has summarized some of this history.

The endogenous-biology angle is similar to DMT: bufotenin has been detected in mammalian urine and brain at very low concentrations, mostly as a metabolite of 5-hydroxytryptamine via INMT methylation. Whether it has any functional role is unclear.

For research bufotenin is mostly of pharmacological-curiosity interest. The poor CNS penetration makes it a difficult in vivo tool, the peripheral cardiovascular pharmacology is intense enough to confound interpretation at most doses, and there are cleaner tryptamine tools for almost any specific receptor question you might want to probe.

Sourcing: synthetic bufotenin or the fumarate/hemifumarate salts are available from specialized suppliers, regulated similarly to other tryptamines in most jurisdictions. HPLC verification is straightforward.

What we like: historical pharmacological interest, useful in comparative tryptamine SAR work where you want a hydroxylated control alongside DMT, 5-MeO-DMT, and bufotenine analogs.

What we dont like: poor BBB penetration limits CNS use, intense peripheral pharmacology confounds in vivo work, thin clinical evidence base, regulatory complexity.

Mostly a historical compound. Limited modern research use case.

Evidence: 25
Mechanism: 60
Reliability: 50
Safety: 50
Sourcing: 45
Value: 50
Signal: 35
Staying power: 40

Plain-language summary Intrigue 44 / 100

Bufotenin is the 5-hydroxyl version of N,N-DMT, found in Anadenanthera seeds (used for the South American snuffs yopo and cohoba) and in Bufo amphibian secretions. The hydroxyl group hurts blood-brain barrier penetration, so peripheral serotonin-like effects (vasoconstriction, nausea, sweating) tend to dominate any central activity. Whether bufotenin produces a meaningful psychedelic experience by typical routes is contested in the literature, with intramuscular and pulmonary routes producing variable reports. The compound is important historically and ethnobotanically but is rarely used in modern psychedelic research because of the awkward pharmacokinetic profile. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Tryptamine / 5-HT2A agonist

5-hydroxy-N,N-dimethyltryptamine; a tryptamine related to DMT and serotonin; found in Anadenanthera seeds and toad secretions.

Abstract

Bufotenin (5-hydroxy-N,N-dimethyltryptamine, 5-HO-DMT; CAS 487-93-4; molecular formula C12H16N2O; molecular weight 204.27) is a tryptamine isolated from Anadenanthera seeds (used for South American snuffs called yopo and cohoba) and from Bufo amphibian secretions. Structurally bufotenin is the 5-hydroxy analog of N,N-DMT and the N,N-dimethyl analog of serotonin. Pharmacology: 5-HT2A agonism with poor blood-brain barrier penetration owing to the polar 5-hydroxy group; the central versus peripheral effect ratio is shifted toward peripheral 5-HT effects (cardiovascular, sympathetic) compared to DMT. The compound's psychoactivity in humans has been debated for decades, with some 1950s and 1960s studies reporting psychotic-like effects (confounded by toxicity) and other studies suggesting limited central activity. Schedule I in the US. Used as a research probe for 5-HT2A pharmacology and as a comparator to DMT in tryptamine structure-activity studies.

Mechanism of action

5-HT2A agonist; poor blood-brain barrier penetration owing to 5-hydroxyl group. Central activity disputed; peripheral 5-HT effects dominant.

Reported research dose ranges

Sparse human pharmacokinetic data; rodent research 1 to 10 mg/kg.

References

Fabing HD, Hawkins JR. Intravenous bufotenine injection in the human being. Science 1956.
McBride MC. Bufotenine: toward an understanding of possible psychoactive mechanisms. J Psychoactive Drugs 2000.
Torres CM, Repke DB. Anadenanthera: visionary plant of ancient South America. Haworth Press 2006.

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KDC-MN-342

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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Bufotenin

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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