Bufotenine is a hallucinogenic tryptamine found naturally in the human brain, select animals and plants.

Endogenous Bufotenine

Bufotenine occurs naturally in human beings. It's quantity varies greatly in individuals.

Elevated urine levels of bufotenine have been found in patients with autistic spectrum disorders and schizophrenia. One study found urine bufotenine levels were significantly higher in autistic spectrum disorder subjects (3.30 +/- 0.49 microg/L, p<0.05) and patients with schizophrenia (4.39 +/- 0.43 microg/L, p<0.001) compared with controls (1.53 +/- 0.30 microg/L).[3] Other studies have found no bufotenine in the urine of normal subjects, but detected it in the urine of schizophrenics.[2]

Bufotenine Controversy

Because of bufotenine's low lipid solubility, bufotenine was once believed to be unable to cross the blood brain barrier in amounts sufficient to illicit hallucinogenic effects. This logic has been proven wrong. Bufotenine's XLogP3 is 1.2, while mescaline's XLogP3 is a mere 0.7. Mescaline has far less lipid solubility, and is still able to produce strong hallucinogenic effects. Modern tests have shown that bufotenine is a more potent hallucinogen requiring smaller doses for hallucinogenic activity.[7]

Bufotenine is active orally, sublingually, intrarectally, intranasally, by inhalation and injection.[7]

Doses as small as 8 mg injected intravenously were shown to produce hallucinogenic activity in human test subjects.[15]

Doses as small as 2 mg of the freebase inhaled as vapor have shown psychoactivity.[7] Doses as small as 8 mg of the freebase inhaled as vapor produced very clear hallucinogenic effects.[7]

Hallucinogenic drugs such as DMT and LSD bind and activate 5-HT2A and 5-HT2C receptor sites. These receptor cites are required for hallucinogenic activity in humans.

In vitro tests show that bufotenine is able to activate 5-HT2A and 5-HT2C receptor sites.[15]

Current computer modeling of human 5-HT2A and 5-HT2C receptor cites also give evidence of bufotenine's ability to bind and activate these receptors, indicating that bufotenine should have hallucinogenic properties in humans.[4]

Yopo snuff, reported as a potent hallucinogen by shamans, is made from Anadenanthera seeds containing bufotenine as the only compound in quantities large enough to elicit effects.[7][1]

Takini was found to contain bufotenine as its active compound. Takini is well known for it's use as a hallucinogen by shamans.[8]

Some tests have found bufotenine active via injection.[10] However, numerous tests via injection of water soluble forms of bufotenine show little hallucinogenic activity.[7] Unfortunately, some of these reports used psychiatric patients, many of which are probably naturally high in bufotenine, and likely to be less susceptible to it's hallucinogenic effects.

Despite overwhelming evidence of bufotenine's hallucinogenic effects, some individuals are unable to obtain hallucinogenic effects from bufotenine at normal dosages. The reason for this is currently unknown. Because some test subjects do not experience hallucinogenic effects from bufotenine, this has caused some researchers to doubt it's activity as a hallucinogen.

In reality, the fact the bufotenine isn't hallucinogenic at normal doses in all individuals is not that much of a surprise. Even LSD, a well known extremely powerful hallucinogen, produces no hallucinogenic effects whatsoever in some individuals at normal doses.

Most modern users of bufotenine only use it in it's freebase form, finding salt forms unpleasant with little hallucinogenic activity. The most common route of administration is by insufflation or inhalation of the freebase form. Traditional use of bufotenine by shamans is by insufflation of yopo snuff, which is very specifically freebased prior to insufflation.

Reports from individuals that are highly susceptible to it's hallucinogenic effects, note that tolerance to it's hallucinogenic effects builds rapidly if used repeatedly.

To help explain why some individuals obtain no hallucinogenic effects from bufotenine, one theory states that if an individual is naturally very high in bufotenine, it stands to reason that they would have a natural high level of tolerance to it's hallucinogenic effects, such that it could be impossible for such an individual to obtain any noticeable hallucinogenic effects from bufotenine.

Another theory is that bufotenine is not hallucinogenic, but a metabolite of it is, and that certain individuals lack the proper enzymes to catalyze the conversion of bufotenine to an active hallucinogenic metabolite.

Both theories are speculative at this time.

Human Metabolism

In humans P450 2D6 (CYP2D6) can create bufotenin from 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) via O-demethylation.

In humans, bufotenin's major metabolite is 5-hydroxyindoleacetic acid, created by the action of Monoamine Oxidase A, but not Monoamine Oxidase B. Tests performed on rats also show that bufotenine is primarily metabolized by Monoamine Oxidase A.[5]

A conjugated metabolite of bufotenine has been found in normal human urine. Conjugation of bufotenine is possible because of the phenolic hydroxyl group on the molecule. Test showed that 59.9 - 69.0% of bufotenine was excreted in conjugated form. The conjugated form of bufotenine was tentatively identified as bufotenine glucuronide, a conjugate of bufotenine and glucuronic acid.[11] Bufotenine glucuronide has been positively identified as a metabolite of bufotenine in rat urine.[1] Glucuronidation of bufotenine is likely catalyzed by Glucuronosyltransferase.

UGT1A9, a glucuronosyltransferase enzyme primarily active towards phenols (bufotenine and psilocin are phenols), is abundantly expressed in both the liver and kidneys, and is believed to be the main contributor to psilocin glucuronidation in vivo.[16] UGT1A10 also contributes to it's glucuronidation, but is believed to be a minor route.[16] Because of the extreme chemical similarity between bufotenine and psilocin, it's very likely that UGT1A9 is also the major enzyme responsible for the creation of bufotenine glucuronide.

Valerian root oil, licorice, and Genistein (in Kudzu) are potent inhibitors of UGT1A9 in vitro. Combining UGT1A9 inhibitors with bufotenine should reduce the quantity of bufotenine glucuronide as a metabolite. This could possibly alter the effects of bufotenine, maybe reducing bodily side effects.

The pharmacology of bufotenine glucuronide in unknown. As an alkaloid, bufotenine glucuronide should remain active, although much less able to cross the blood-brain barrier. It's likely to produce somatic effects, possibly nausea, but should have little if any psychoactivity.

Rat Metabolism

After i.v. administration in rats, the concentration of bufotenine in brain tissue remained very low at all times. The biologic half-life of bufotenine in blood was 40 min. The metabolites in liver, lung and heart were so concentrated relative to unchanged drug that metabolism was probably occurring in these tissues. About 91% of the dose of bufotenine was excreted in 72 hours in urine, most of it in 12 hours. Less than 2% was eliminated in the feces. About 6% was excreted as unchanged bufotenine, 15% was excreted as 5-hydroxyindole acetic acid and 35% was excreted as bufotenine glucuronide, a conjugate of bufotenine and glucuronic acid.[14]

5-hydroxyindole acetic acid is created by the action of Monoamine Oxidase A on bufotenine. With bufotenine glucuronide being the major metabolite, and not 5-hydroxyindole acetic acid, it's clear that glucuronosyltransferase is likely the major route of bufotenine elimination in rats and not the action of Monoamine Oxidase A.

The closely related hallucinogen psilocin also follows a very similar pathway in rats with psilocin glucuronide being the main route of elimination for psilocin create via glucuronosyltransferase.[15]

Therapeutic Uses

Bufotenine shows some antiviral effects. It was found to block rabies virus infection in BHK-21 cells.[6]

Natural Sources

Anadenanthera colubrina and Anadenanthera peregrina seeds contain substantial amounts of bufotenin. Seeds of Anadenanthera colubrina have been found to contain up to 12.4% bufotenine.[1]

Brosimum acutifolium Huber subsp. acutifolium C.C, also known as takini, is another natural source of bufotenine.[8]

Bufotenine was found in the skin secretion of three arboreal amphibian species from the Amazon and the Atlantic rain forests: Osteocephalus taurinus, Osteocephalus oophagus and Osteocephalus langsdorffii.[9]

Tetrapterys mucronata stem bark, an ingredient found sometimes in ayahuasca, was found to contain 0.326 % bufotenine, 0.307% 5-methoxy-bufotenine (5-MeO-DMT), 0.088% 5-methoxy-N-methyltryptamine, and 0.0004% 2-methyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline.[20] Because 5-methoxy-bufotenine is roughly the same potency as bufotenine, the general effects felt will be from a near equal mix of the effects of these two alkaloids.

Hydroxyl Group Reactivity

Some speculation exists on the potential reactivity of the acidic phenolic hydroxyl group at the 5 position on bufotenine.

It's known that the phenolic hydroxyl group on bufotenine allows a conjugated metabolite of bufotenine to be formed, which is present in urine. This conjugate is known as bufotenine glucuronide. It's proven to occur in rats.[1] Tests also suggest it occurs in humans.[11]

The Merck Index specifically states that bufotenine freebase is soluble in dilute acids and alkalies but almost insoluble in water[12]. This information lends credit to the ability of the hydroxyl group to form salts with bases and the amine group to form salts with acids.

It's known that similar compounds, such as morphine, with an acidic hydroxyl group, can form water soluble salts with bases such as calcium carbonate, calcium hydroxide, etc. Calcium morphenate is the chemical name for the calcium salt of morphine, used in the isolation of morphine from other opium alkaloids.

Similarly, eugenol's hydroxyl group is able to form salts with calcium and sodium bases. Calcium eugenate can be created by simply mixing eugenol with a saturated aqueous solution of calcium hydroxide.

When isolating eugenol from the other constituents of clove oil, the preparation of sodium eugenate is often used. For this method of eugenol isolation, an aqueous solution of sodium hydroxide is mixed with clove oil. This causes the oil soluble eugenol to form the water soluble sodium eugenate, which then migrates into the water layer of the oil/water mix, leaving the other oils in the oil layer. The sodium eugenate solution can then be easily separated from the other oils in clove oil. After separation, sodium eugenate is converted back to eugenol using a weak acid.

According to the data in the Merck Index, sodium or calcium salts of bufotenine appear to be possible. However, many attempts at isolating dry sodium bufotenate and calcium bufotenate have failed. No studies have been identified showing that sodium bufotenate or calcium bufotenate exist out of solution.

Yopo Snuff

Anadenanthera colubrina or Anadenanthera peregrina seeds are used to make yopo snuff. Both seeds contain bufotenine as their only active alkaloid.

Authentic yopo snuff prepared in South America by skilled shamans is claimed to have effects that are more similar to DMT than to that of bufotenine.

It is believed that the different effects are caused the shamans using a special snuff making process that dehydrogenates bufotenine into dehydrobufotenine. This is however just speculation.

For more details see the The Yopo Transformation Theory article.

Chemical Properties

Bufotenine Freebase

Appearance: Stout prisms from ethyl acetate[12]; Transparent prisms (monoclinic)[18]. White crystalline powder[21]

  • Bufotenine
  • Bufotenin
  • N,N-Dimethyl-5-hydroxytryptamine
  • N,N Dimethyl 5 hydroxytryptamine
  • N,N-Dimethylserotonin
  • Cinobufotenine
  • Mappin
  • Mappine
  • 5 Hydroxy N,N dimethyltryptamine
  • 5-Hydroxy-N,N-dimethyltryptamine
  • Dimethylserotonin

IUPAC Name: 3-[2-(dimethylamino)ethyl]-1H-indol-5-ol
Molecular Formula: C12H16N2O
Molecular Weight: 204.26824 g/mol
Melting Point: 146-147 C[12][1], 123-124 C[1] depending on the crystal structure.[18]
Boiling Point: 320 C[12]
UV: λmax 220, 265 nm (log e 4.0, 3.7) [12]
XLogP3: 1.2
ACD/Labs Predicted LogP: 0.891
CAS No: 487-93-4
EC Number: 207-667-9
UNII: 0A31347TZK
pKa (amino group): 9.67[13][18]
pKa (hydroxyl group): 10.88[18]
Fluorescence: Reported to have a weak violet fluorescence; Faint yellow fluorescence under 350 nm UV; Activation: 310 nm, Emission: 360 nm (pH 7.4); Activation: 310, Emission: 360 nm (pH 7); Activation: 310, Emission: 360 nm (pH 2)[18]
InChI: InChI=1S/C12H16N2O/c1-14(2)6-5-9-8-13-12-4-3-10(15)7-11(9)12/h3-4,7-8,13,15H,5-6H2,1-2H3
Canonical SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)O
PubChem CID: 10257
Crystallization Solvents: ethyl acetate; acetone/ether; acetone[18]
Crystallization Procedures:

  • dissolve in D-limonene at 176 C, bufotenine will crystallize out of solution as it cools to room temperature.[19]
  • dissolve in heptane with 50% MEK. Slowly add heptane until crystals begin to form.[19]
  • dissolve in xylene at 144 C, bufotenine will crystallize out of solution as it cools to room temperature.[19]

Bufotenine Freebase Solubility

Freely soluble in methanol[21]; freely soluble in alcohol[12], less soluble in ether[12]; almost insoluble in water[12]; insoluble in water[21]; slightly soluble in ether[21]; soluble in dilute acids and alkalies[12][21]; soluble in ethanol, chloroform and ethyl acetate[17]; soluble in butanol[17].

Bufotenine Freebase Solubility (Anonymous Source)

NOTE: No references are available for the data in this section. It appears to be accurate data on the solubility of bufotenine freebase. This data appears on several web sites. It originates from a trusted anonymous researcher, and has not been disputed.

Acetone @ 20 C: soluble (5 g/100 ml)
Chloroform @ 20 C: soluble
Dichloromethane @ 20 C: soluble
Dimethyl sulfoxide (DMSO) @ 20 C: soluble (6 g/100 ml)
D-Limonene (Orange Oil) @ 20 C: insoluble
D-Limonene (Orange Oil) @ 176 C: soluble (more than 1.7 g/100 ml)
Ethanol @ 20 C: soluble
Ether @ 20 C: soluble
Ethyl acetate @ 20 C: soluble
Heptane @ 20 C: insoluble
Heptane with 40% MEK @ 20 C: soluble (0.53 g/100 ml)
Heptane with 50% MEK @ 20 C: soluble (1.22 g/100 ml)
IPA @ 20 C: soluble
MEK @ 20 C: soluble
Methanol @ 20 C: soluble
Naphtha @ 20 C: insoluble
Water @ 20 C: nearly insoluble in pure water (no acid or alkali added)
Xylene @ 20 C: nearly insoluble (less than 0.03 g/100 ml)
Xylene @ 144 C: soluble (1.5 g/100 ml)

Bufotenine Flavianate:

Appearance: Red needles from water[18]
Melting Point: 130-131 C, 131-133 C[18]

Bufotenine Fumarate:

Melting Point: 228-230 C with decomposition (from ethanol)[18]

Bufotenine Hydrogen Oxalate:

Appearance: Needles from MeOH[18]. Lavender to brown powder[21]
Melting Point: 89-90 C[18]; 97-99 C[21]
Solubility: freely soluble in methanol; very soluble in water; very slightly soluble in acetone; slightly soluble in chloroform; insoluble in ether, hexane.[21]
Isolation: Being slightly soluble in chloroform, bufotenine hydrogen oxalate can be easily separated from chloroform insoluble material.[21]

Bufotenine Monooxalate:

Appearance: Pink needles[18]; Light tan solid.
Melting Point: 93-94 C[18]
Solubility: Soluble in water.

Bufotenine Monopicrate:

Appearance: Yellow crystals which change to a red modification at 120-
140 C; Yellow picrate from EtOH; Both red (long needles) and yellow (short prisms); Red picrate changing to yellow at 140 C; Yellow picrate (from ethanol); Yellow monopicrate (from water)[18]
Melting Point: 177.5 C, 177-178 C, 179-180 C[18]

Bufotenine Dipicrate:

Appearance: Red; Red prisms from methanol; Dark red; Boiling in benzene produced yellow monopicrate; Red crystals from MeOH[18]
Melting Point: 172-173 C, 174 C, 175-177 C, 176-177 C, 177-178 C, 179 C from boiled benzene, 176-177 C from MeOH[18]

Bufotenine Picrolonate:

Appearance: Small yellow prisms[18]
Melting Point: 120-121 C, 110 C, 120-121 C from ethanol, 130-131 C, 183-184 C[18]

Bufotenine Methiodide:

Molecular Formula: C13H19IN2O[12]
Appearance: Stout prisms from methanol[12]; Colorless prisms; Colorless crystals[18]
Decomposition: 214-215 C[12], 209 C, 210 C, 210-211 C, 210-211 C from ethanol, 213-215 C[18]

See also

Bufotenine N-Oxide
The Yopo Transformation Theory

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Moretti C, Gaillard Y, Grenand P, Bévalot F, Prévosto JM.; J Ethnopharmacol. 2006 Jun 30;106(2):198-202. Epub 2006 Feb 7.; PMID: 16455218
9. Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae).
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15. Studies in Natural Products Chemistry, Volume 46
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16. Glucuronidation of Psilocin and 4-Hydroxyindole by the Human UDP-Glucuronosyltransferases
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18. Some Simple Tryptamines
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19. NOTE: No references are available for this data. It appears to be accurate data. This data appears on several web sites. It originates from a trusted anonymous researcher, and has not been disputed.
20. LC-MS/MS quantitative determination of Tetrapterys mucronata alkaloids, a plant occasionally used in ayahuasca preparation.
Queiroz MM, Marti G, Queiroz EF, Marcourt L, Castro-Gamboa I, Bolzani VS, Wolfender JL.; Phytochem Anal. 2015 May-Jun;26(3):183-8. doi: 10.1002/pca.2548. Epub 2015 Jan 26.; PMID: 25620461 Scientific Working Group for the Analysis of Seized Drugs. August 16, 2005
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