Bufotenin

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Bufotenin
Bufotenin2DACS.svg
Bufotenin-3d-sticks.png
Systematic (IUPAC) name
3-(2-Dimethylaminoethyl)-1H-indol-5-ol
Clinical data
Oral, intravenous
Identifiers
487-93-4 YesY
None
PubChem CID 10257
IUPHAR ligand 144
DrugBank DB01445 YesY
ChemSpider 9839 YesY
KEGG C08299 YesY
ChEBI CHEBI:3210 YesY
ChEMBL CHEMBL416526 YesY
Synonyms N,N-dimethyl-5-hydroxytryptamine, 5-hydroxy-dimethyltryptamine, bufotenine, cebilcin
Chemical data
Formula C12H16N2O
204.268 g/mol
Physical data
Melting point 146 to 147 °C (295 to 297 °F)
Boiling point 320 °C (608 °F)
 YesY (what is this?)  (verify)

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. [1]

The name bufotenin originates from the Bufo genus of toads, which includes several species of toads that release bufotoxin from their paratoid glands. [2] The drug was first isolated from a toad during World War 1. While the drug comes naturally from a toad, it can also be synthesized in a lab starting from 5-Benzyloxiyindole.

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 pscilon (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.

Nomenclature[edit]

Bufotenin (bufotenine) is also known by the chemical names 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), N,N-dimethyl-5-hydroxytryptamine, dimethyl serotonin,[3] and mappine.[3]

History[edit]

Bufotenin was first isolated from toad skin, and named by the Austrian chemist Handovsky at the University of Prague during World War I.[4] 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.[5] 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. During the 1980’s, bufotenin started becoming recreationally used due to it's hallucinogenic effect.


Sources[edit]

Toads[edit]

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.[6]

Bufo periglenes

The toad was "recurrently depicted in Mesoamerican art,"[7] 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.[6]

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,[8][9][10] some of which resulted in death.[10][11][12]

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[13]), ingested orally in the form of ch’an su,[10] 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.[10][14] 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.[15][16] 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[17][18] 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.[19]

Anadenanthera seeds[edit]

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.[20]

Other sources[edit]

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,[21] and in the seeds of Mucuna pruriens [22]

Synthesis[edit]

Synthesis of Bufotenin

One of the ways to synthesize Bufotenin is through treating 5-benzyloxyindole with oxalyl chloride, followed by dimethylamine, which then produces glyoxlamide. This product can be reduced and after treating the product of that substance with a catalytic debenzylation produces bufotenin. [23]


Pharmacology[edit]

Uptake and elimination[edit]

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.[24] 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.

Like other hallucinogenic drugs, bufotenin binds to two different receptors, 5-HT2A and 5-HT2C. 5-HT2A and 5-HT2C are two receptors that are closely related to the neurotransmitter serotonin, they are closely related to the drug LSD as well. 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 Bufotenin does not share the same strength as 5-MeO-DMT. This is due to bufotenin has a harder time crossing the brain blood barrier. Therefore the drug is most effective when used intravenously, therefore getting through the blood brain barrier without much problems [25]

Lethal dose[edit]

The acute toxicity (LD50) of bufotenin in rodents has been estimated at 200 to 300 mg/kg. Death occurs by respiratory arrest.[20]

Effects in humans[edit]

Scientist Year Dosage Effects
Fabings and Hawkins 1955 1 mg A tight feeling in the chest. [26]
2 mg Tightness in the throat, stomach, tingling in preitibal areas and vomited for three minutes. [26]
4 mg Numbness of the entire body. Euphoric feeling. Reports of red spots passing before his eyes. [26]
Dr. Harris Isbell 1956 10-12 mg Elements of visual hallucination consisting of a play of colors, light and patterns.[4]
Turner and Merlis 1959 10 mg Extreme peripheral nervous system effects. At 17 seconds: flushing of the face. 22 seconds: maximum inhalation. Followed by maximal hyperventilation for the next two minutes. [27]
McLeod and Sitaram 1985 2-4 mg No effects[28]
8 mg Profound emotional and perceptual change.[28]
Otts 2001 40 mg Visionary effects.[29]
100 mg (ingested orally) More extreme visionary effects that included swirling color patterns.[29]
  • All doses were given intravenously unless stated otherwise.

Association with schizophrenia and other mental disorders[edit]

A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects;[30] however, subsequent research has failed to confirm these findings.[31][32][33][34]

Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders,[35] such as infant autistic patients.[36] 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.[37]

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.[38]

Legal status[edit]

Australia[edit]

Bufotenin is classified as a Schedule I controlled substance according to the Criminal Code Regulations of the Government of the Commonwealth of Australia.[39]

United Kingdom[edit]

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

United States[edit]

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.[40]

Pop Culture[edit]

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.

See also[edit]

References[edit]

  1. ^ CID 10257. PubChem. Accessed on May 6, 2007.
  2. ^ Bufo Alvarius. AmphibiaWeb. Accessed on May 6, 2007.
  3. ^ a b "DEA Drug Scheduling". U.S. Drug Enforcement Administration. Retrieved 2007-08-11. 
  4. ^ a b Chilton WS, Bigwood J, Jensen RE (1979). "Psilocin, bufotenine and serotonin: historical and biosynthetic observations". J Psychedelic Drugs. 11 (1–2): 61–9. doi:10.1080/02791072.1979.10472093. PMID 392119. 
  5. ^ "Synthese des Bufotenins und über 3-Methyl-3-β-oxyäthyl-indolenin. Synthesen in der Indol-Gruppe. XIV". Justus Liebig's Annalen der Chemie 520 (1). 1935. pp. 19–30. doi:10.1002/jlac.19355200104. Retrieved 2014-01-26. 
  6. ^ a b Davis W, Weil A (1992). "Identity of a New World Psychoactive Toad". Ancient Mesoamerica 3: 51–9. doi:10.1017/s0956536100002297. 
  7. ^ Kennedy AB (1982). "Ecce Bufo: The Toad in Nature and in Olmec Iconography". Current Anthropology 23 (3): 273–90. doi:10.1086/202831. 
  8. ^ Hitt M, Ettinger DD (1986). "Toad toxicity". N Engl J Med 314 (23): 1517–8. doi:10.1056/NEJM198606053142320. PMID 3702971. 
  9. ^ Ragonesi DL (1990). "The boy who was all hopped up". Contemporary Pediatrics 7: 91–4. 
  10. ^ a b c d Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS (1996). "Treatment of toad venom poisoning with digoxin-specific Fab fragments". Chest 110 (5): 1282–8. doi:10.1378/chest.110.5.1282. PMID 8915235. 
  11. ^ Gowda RM, Cohen RA, Khan, IA (2003). "Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications". Heart 89 (4): e14. doi:10.1136/heart.89.4.e14. PMC 1769273. PMID 12639891. 
  12. ^ Lever, Christopher (2001). The Cane Toad: The History and Ecology of a Successful Colonist. Westbury Academic & Scientific Publishing. ISBN 1-84103-006-6. 
  13. ^ http://www.ehealthstrategies.com/files/aphrodisia.pdf
  14. ^ Centers for Disease Control and Prevention (CDC) (1995). "Deaths associated with a purported aphrodisiac—New York City, February 1993-May 1995". MMWR Morb Mortal Wkly Rep 44 (46): 853–5, 861. PMID 7476839. 
  15. ^ The Dog Who Loved to Suck on Toads. NPR. Accessed on May 6, 2007.
  16. ^ Psychoactive toad: Cultural references
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  18. ^ How ‘bout them toad suckers? Ain’t they clods? Smoky Mountain News. Accessed on May 6, 2007
  19. ^ Costa TO, Morales RA, Brito JP, Gordo M, Pinto AC, Bloch C Jr. (2005). "Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae)". Toxicon 46 (4): 371–5. doi:10.1016/j.toxicon.2005.02.006. PMID 16054186. 
  20. ^ a b David B. Repke, Constantino Manuel Torres (2006). Anadenanthera: visionary plant of ancient South America. New York: Haworth Herbal Press. ISBN 0-7890-2642-2. 
  21. ^ Moretti C, Gaillard Y, Grenand P, Bévalot F, Prévosto JM (2006). "Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic potion used in the Guiana Plateau". J Ethnopharmacol 106 (2): 198–202. doi:10.1016/j.jep.2005.12.022. PMID 16455218. 
  22. ^ Chamakura RP (1994). "Bufotenine—a hallucinogen in ancient snuff powders of South America and a drug of abuse on the streets of New York City". Forensic Sci Rev. 6 (1): 2–18. 
  23. ^ Downing, D.F. (1971). "THE CHEMISTRY OF THE PSYCHOTOMIMETIC SUBSTANCES". Chemical Society (4): 455 Extra |pages= or |at= (help). 
  24. ^ Fuller RW, Snoddy HD, Perry KW (1995). "Psilocin Tissue distribution, metabolism and effects of bufotenine administered to rats". Neuropharmacology 34 (7): 799–804. doi:10.1016/0028-3908(95)00049-C. PMID 8532147. 
  25. ^ McBride, Michael (Jul-Sept 2000). "Bufotenine: Toward an Understanding of Possibly Psychoactive Mechanisms". J Psychoactive Drugs 32 (3): 321-331.  Check date values in: |date= (help);
  26. ^ a b c Fabing HD, Hawkins, JR (1956). "Intravenous bufotenine injection in the human being". Science 123 (3203): 886–7. doi:10.1126/science.123.3203.886. PMID 13324106. 
  27. ^ Turner WJ, Merlis S. (1959). "Effects of some indolealkylamines on man". Arch Neurol Psychiatr. 81 (1): 121–9. doi:10.1001/archneurpsyc.1959.02340130141020. PMID 13605329. 
  28. ^ a b McLeod WR, Sitaram BR (1985). "Bufotenine reconsidered". Acta Psychiatrica Scandinavica 72 (5): 447–50. doi:10.1111/j.1600-0447.1985.tb02638.x. PMID 4091027. 
  29. ^ a b Ott J (2001). "Pharmanopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine". J Psychoactive Drugs 33 (3): 273–81. doi:10.1080/02791072.2001.10400574. PMID 11718320. 
  30. ^ Faurbye A, Pind K (November 1968). "Occurrence of bufotenin in the urine of schizophrenic patients and normal persons". Nature 220 (5166): 489. doi:10.1038/220489a0. PMID 5686166. 
  31. ^ Siegel M (October 1965). "A sensitive method for the detection of n,n-dimethylserotonin (bufotenin) in urine; failure to demonstrate its presence in the urine of schizophrenic and normal subjects". J Psychiatr Res 3 (3): 205–11. doi:10.1016/0022-3956(65)90030-0. PMID 5860629. 
  32. ^ Pomilio AB, Vitale AA, Ciprian-Ollivier J, Cetkovich-Bakmas M, Gómez R, Vázquez G. (1999). "Ayahoasca: an experimental psychosis that mirrors the transmethylation hypothesis of schizophrenia". J Ethnopharmacol 65 (1): 29–51. doi:10.1016/S0378-8741(98)00163-9. PMID 10350367. 
  33. ^ Ciprian-Ollivier J, Cetkovich-Bakmas MG (1997). "Altered consciousness states and endogenous psychoses: a common molecular pathway?". Schizophrenia Research 28 (2–3): 257–65. doi:10.1016/S0920-9964(97)00116-3. PMID 9468359. 
  34. ^ Carpenter WT Jr, Fink EB, Narasimhachari N, Himwich HE (1975). "A test of the transmethylation hypothesis in acute schizophrenic patients". Am J Psychiatry 132 (10): 1067–71. doi:10.1176/ajp.132.10.1067. PMID 1058643. 
  35. ^ Takeda N, Ikeda R, Ohba K, Kondo M (November 1995). "Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders". NeuroReport 6 (17): 2378–80. doi:10.1097/00001756-199511270-00024. PMID 8747157. 
  36. ^ Takeda N (February 1994). "Serotonin-degradative pathways in the toad (Bufo bufo japonicus) brain: clues to the pharmacological analysis of human psychiatric disorders". Comp Biochem Physiol Pharmacol Toxicol Endocrinol 107 (2): 275–81. doi:10.1016/1367-8280(94)90051-5. PMID 7749594. 
  37. ^ Räisänen MJ, Virkkunen M, Huttunen MO, Furman B, Kärkkäinen J (September 1984). "Increased urinary excretion of bufotenin by violent offenders with paranoid symptoms and family violence". Lancet 2 (8404): 700–1. doi:10.1016/S0140-6736(84)91263-7. PMID 6147728. 
  38. ^ Emanuele E, Colombo R, Martinelli V, Brondino N, Marini M, Boso M, Barale F, Politi P (2010). "Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia". Neuro Endocrinol Lett 31 (1): 117–21. PMID 20150873. 
  39. ^ Criminal Code Regulation 2005 (SL2005-2) (RTF), Australian Capital Territory, May 1, 2005, retrieved 2007-08-12 
  40. ^ §1308.11 Schedule I.

External links[edit]