spec sheet11 rows
Bufotenine (5-hydroxy-N,N-dimethyltryptamine) is a naturally occurring tryptamine and a positional isomer of psilocin, found in the seeds of Anadenanthera trees used to make the South American shamanic snuffs yopo and cebil, in the skin secretions of Bufo toads, and in some mushrooms. Pharmacologically it is a serotonergic agonist active at 5-HT2A and 5-HT2C receptors, the same receptors engaged by classic hallucinogens, and computational and in vitro studies confirm it can bind and activate them. Its psychoactivity in humans has long been debated, however, because its ionizable 5-hydroxy group limits passage across the blood-brain barrier, so much of an ingested dose acts peripherally; intravenous administration in early human experiments produced profound but very short-lived perceptual and emotional changes. That poor central penetration, combined with strong peripheral cardiovascular and autonomic effects, makes bufotenine a physiologically demanding and higher-risk substance. It is a controlled Schedule I compound.
- A serotonergic tryptamine and positional isomer of psilocin
- Active at 5-HT2A and 5-HT2C receptors in vitro
- Central to the pharmacology of traditional Anadenanthera snuffs
- Illustrates how a single ring substituent governs brain penetration
- Intense facial flushing and chest or throat constriction
- Marked cardiovascular and autonomic strain
- Nausea and physical distress
- Unpredictable potency from toad or plant sources
- Dangerous potentiation when combined with MAO inhibitors
Mechanism
Bufotenine is a substituted tryptamine, an isomer of psilocin bearing its hydroxyl group at the 5-position of the indole ring, which makes it structurally a dimethylated . Like other serotonergic hallucinogens it acts as an at serotonin and 5-HT2C receptors, and receptor-binding and computational modeling studies show it engages and activates these sites in a manner comparable to LSD, psilocin, and 5-MeO-DMT. The central pharmacological puzzle of bufotenine is the mismatch between this clear receptor activity and its inconsistent hallucinogenic effects in humans. The prevailing explanation is pharmacokinetic: the 5-hydroxy group is ionizable at physiological pH, giving the molecule poor lipophilicity and limited ability to cross the , so a large fraction of an ingested or injected dose exerts peripheral serotonergic effects rather than reaching central receptors. Molecular dynamics simulations of tryptamines in lipid bilayers are consistent with this, showing that bufotenine partitions into membranes yet, unlike its relatives, does not readily pass through them.
This blood-brain-barrier limitation shapes both its route dependence and its risk profile. Human self-experiments across intranasal, sublingual, rectal, inhaled, and oral routes, some combined with monoamine oxidase-inhibiting beta-carbolines to effects, form much of the available psychonautic evidence, and traditional Anadenanthera snuffs exploit exactly this potentiation. When bufotenine has been given intravenously, it correlated with rapid, intense, and brief perceptual and emotional changes before being cleared quickly and excreted in the urine as metabolites. Its close methylated analogue 5-MeO-DMT (O-methylbufotenine), by contrast, is far more and centrally active, which highlights how a small change to that 5-position substituent transforms brain penetration. Bufotenine has also been reported to have peripheral pharmacological actions independent of its psychoactivity, including in vitro antiviral activity against certain viruses.
receptor fingerprint
receptoragonist
5-HT2C receptoragonist
Peripheral receptors and vasculatureagonist
penetrationpoor (ionizable 5-hydroxy group)
Safetyrisks and cautions, not medical advice
Bufotenine is a physiologically demanding tryptamine that warrants serious caution and is a controlled Schedule I substance. Because much of a dose acts peripherally rather than centrally, prominent effects can include intense facial flushing, a sense of chest or throat constriction, marked cardiovascular changes, nausea, and autonomic distress, and early human experiments described these somatic reactions as severe even when psychological effects were brief.
Material sourced from toad secretions or crude plant snuffs carries added dangers from co-occurring toxins and from unpredictable potency, and traditional preparations are frequently combined with monoamine oxidase inhibitors, which can dangerously potentiate serotonergic effects and raise the risk of a hypertensive or serotonergic crisis. It should not be combined with other serotonergic drugs or MAO inhibitors, and it is inappropriate for anyone with cardiovascular disease or a personal or family history of psychosis. Human data remain sparse and largely anecdotal, so its effects and risks are poorly quantified. Not medical advice.
Subjective profileweighing the evidence above
Poor brain penetration paired with severe cardiovascular and autonomic strain makes this a bad trade by any measure, and toad or crude snuff material adds unpredictable potency on top. Worth understanding as pharmacology; not worth taking.
Resources
This entry is here for reference.
Research
- 1985first citedBufotenine reconsidered
- 2025most recentClassic Psychedelics for the Treatment of Depression: Potential Benefits and Challenges
- 1.Bufotenine reconsidered
- 2.Bufotenine: toward an understanding of possible psychoactive mechanisms
- 3.Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine.
- 4.Bufotenine - A Hallucinogen in Ancient Snuff Powders of South America and a Drug of Abuse on the Streets of New York City
- 5.Interaction of psychedelic tryptamine derivatives with a lipid bilayer
- 6.In vitro effects of bufotenine against RNA and DNA viruses
- 7.Structural pharmacology and therapeutic potential of 5-methoxytryptamines
- 8.A narrative synthesis of research with 5-MeO-DMT
- 9.Classic Psychedelics for the Treatment of Depression: Potential Benefits and Challenges
9 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is bufotenine actually psychedelic?
It is genuinely active at the 5-HT2A and 5-HT2C receptors that classic psychedelics use, but its hallucinogenic effects in people are inconsistent. The likely reason is that its 5-hydroxy group makes it poorly able to cross the blood-brain barrier, so much of a dose acts on the body rather than the brain. Intravenous administration has produced intense but very brief experiences.
How does bufotenine relate to 5-MeO-DMT and psilocin?
Bufotenine (5-HO-DMT) is a positional isomer of psilocin (4-HO-DMT), differing only in where the hydroxyl sits on the indole ring. Methylating that hydroxyl gives 5-MeO-DMT, or O-methylbufotenine, which is far more lipophilic and strongly centrally active. These small structural differences dramatically change how each molecule behaves.
Why is bufotenine considered risky?
Because so much of it acts peripherally, it can cause intense flushing, cardiovascular strain, chest tightness, and autonomic distress. Sources such as toad secretions or crude snuffs add toxins and unpredictable potency, and traditional use with MAO-inhibiting plants can dangerously amplify serotonergic effects. Human safety data are sparse, and it is a Schedule I substance.
Adverse effects
- Intense facial flushing and chest or throat constriction
- Marked cardiovascular and autonomic strain
- Nausea and physical distress
- Unpredictable potency from toad or plant sources
- Dangerous potentiation when combined with MAO inhibitors