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{{Short description|Psychedelic drug found in toads, mushrooms and plants}}
{{drugbox | Verifiedfields = changed
{{Infobox drug
| Watchedfields = changed | Watchedfields = changed
| verifiedrevid = 406751607 | verifiedrevid = 443669819
| image = Bufotenin2DACS.svg
|
| width =
| IUPAC_name = 3-(2-dimethylaminoethyl)-1''H''-indol-5-ol
| image = Bufotenin Structural Formulae V.1.svg
| image2 = Bufotenin-3d-sticks.png | image2 = Bufotenin-3d-sticks.png
| width = 260 | width2 =

| width2 = 150
<!--Clinical data-->
| tradename =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU = S9
| legal_CA = Unscheduled
| legal_DE = NpSG
| legal_UK = Class A
| legal_US = Schedule I
| legal_status = Illegal in ]
| routes_of_administration = Oral, intravenous

<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound =
| metabolism =
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 487-93-4
| ATC_prefix = None
| ATC_suffix =
| PubChem = 10257
| IUPHAR_ligand = 144
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01445
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9839 | ChemSpiderID = 9839
| KEGG_Ref = {{keggcite|changed|kegg}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0A31347TZK
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08299 | KEGG = C08299
| ChEBI_Ref = {{ebicite|correct|EBI}}
| InChI = 1/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
| InChIKey = VTTONGPRPXSUTJ-UHFFFAOYAH
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VTTONGPRPXSUTJ-UHFFFAOYSA-N
| CAS_number = 487-93-4
| ATC_prefix = none
| ATC_suffix =
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 3210 | ChEBI = 3210
| DrugBank = DB01445
| PubChem = 10257
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 416526 | ChEMBL = 416526
| synonyms = Bufotenine; 5-Hydroxy-''N'',''N''-dimethyltryptamine; 5-HO-DMT; 5-OH-DMT; ''N'',''N''-Dimethyl-5-hydroxytryptamine; ''N'',''N''-Dimethylserotonin; Dimethylserotonin; Dimethyl-5-HT; Cebilcin; Mappine
| IUPHAR_ligand = 144

| synonyms = N,N-dimethyl-5-hydroxytryptamine, 5-hydroxy-dimethyltryptamine, bufotenine, cebilcin
<!--Chemical data-->
| IUPAC_name = 3--1''H''-indol-5-ol
| C=12 | H=16 | N=2 | O=1 | C=12 | H=16 | N=2 | O=1
| SMILES = CN(C)CCc1cc2ccc(O)cc12
| molecular_weight = 204.268 g/mol
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| smiles = Oc1cc2c(cc1)ncc2CCN(C)C
| StdInChI = 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
| boiling_point = 320
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VTTONGPRPXSUTJ-UHFFFAOYSA-N

<!-- Physical data -->
| melting_point = 146 | melting_point = 146
| melting_high = 147 | melting_high = 147
| bioavailability = | boiling_point = 320
| protein_bound =
| metabolism =
| elimination_half-life =
| solubility =
| excretion =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US = Schedule I
| legal_status =
| routes_of_administration = Parenteral
}} }}


'''Bufotenin''', also known as '''dimethylserotonin''' or as '''5-hydroxy-''N'',''N''-dimethyltryptamine''' ('''5-HO-DMT'''), is a ] ], more specifically, a ] (DMT) ], related to the ] ]. It is an ] found in some species of ], ] and ]s, especially the skin. It is also found ] in the human body in small amounts.<ref name="BarkerMcIlhennyStrassman2012">{{cite journal | vauthors = Barker SA, McIlhenny EH, Strassman R | title = A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010 | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 617–635 | date = 2012 | pmid = 22371425 | doi = 10.1002/dta.422 | url = }}</ref><ref name="NeumannDheinKirchhefer2024" /><ref name="KärkkäinenForsströmTornaeus2005">{{cite journal | vauthors = Kärkkäinen J, Forsström T, Tornaeus J, Wähälä K, Kiuru P, Honkanen A, Stenman UH, Turpeinen U, Hesso A | title = Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues | journal = Scand J Clin Lab Invest | volume = 65 | issue = 3 | pages = 189–199 | date = 2005 | pmid = 16095048 | doi = 10.1080/00365510510013604 | url = }}</ref>
'''Bufotenin''' (also known as '''bufotenine''' and '''cebilcin'''), or '''5-hydroxy-dimethyltryptamine''' ('''5-HO-DMT''' or '''5-OH-DMT'''), is a ] related to the ] ]. It is an ] found in the skin of some species of ]s; in ], higher ], and ].<ref> ''].'' Accessed on May 6, 2007.</ref>


The name bufotenin originates from the '']'' genus of toads, which includes several species of ]s (such as '']'' and '']'') that ] ]s from their ]s.<ref> ''AmphibiaWeb.'' Accessed on May 6, 2007.</ref> Bufotenin is similar in chemical structure to the ]s ], ], and ], chemicals which also occur in some of the same fungus, plant, and animal species as bufotenin. Psychedelic effects of bufotenin in humans have been observed in some studies. The name bufotenin originates from the toad genus '']'', which includes several species of ]s, most notably '']'', that ] ]s from their ]s.<ref> ''AmphibiaWeb.'' Accessed on May 6, 2007.</ref> Bufotenin is similar in chemical structure to the ]s ], ] and ], chemicals which also occur in some of the same fungus, plant and animal species as bufotenin.


==Nomenclature== ==Nomenclature==
Bufotenin (bufotenine) is also known by the chemical names 5-hydroxy-dimethyltryptamine (5-HO-DMT), ''N,N''-dimethyl-5-hydroxytryptamine, dimethyl serotonin,<ref name=dea>{{cite web |title = DEA Drug Scheduling| publisher = U.S. Drug Enforcement Agency|url=http://www.usdoj.gov/dea/pubs/scheduling.html|accessdate = 2007-08-11}}</ref> and mappine.<ref name=dea/> Bufotenin (bufotenine) is also known by the names 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), ''N'',''N''-dimethyl-5-hydroxytryptamine, dimethylserotonin, and mappine, among others.<ref name="dea">{{cite web|title = DEA Drug Scheduling|publisher = U.S. Drug Enforcement Administration|url = http://www.usdoj.gov/dea/pubs/scheduling.html|access-date = 2007-08-11|archive-url = https://web.archive.org/web/20081020210309/http://www.usdoj.gov/dea/pubs/scheduling.html|archive-date = 2008-10-20|url-status = dead}}</ref>


==History== ==History==
Bufotenine was first isolated, from toad skin, and named by the Austrian chemist Handovsky at the ] during ].<ref name=chilton>{{cite journal |author=Chilton WS, Bigwood J, Jensen RE|year=1979 |title=Psilocin, bufotenine and serotonin: historical and biosynthetic observations |journal=J Psychedelic Drugs. |volume=11 |issue=1-2 |pages=61–9 |pmid=392119}}</ref> The structure of bufotenine was first confirmed in 1934 by ]’s laboratory in Munich, and the first reported synthesis of bufotenine was by Toshio Hoshino in 1936.<ref name=chilton/> Bufotenin was isolated from toad skin, and named by the Austrian chemist Handovsky at the ] during ].<ref name=chilton>{{cite journal | vauthors = Chilton WS, Bigwood J, Jensen RE | title = Psilocin, bufotenine and serotonin: historical and biosynthetic observations | journal = Journal of Psychedelic Drugs | volume = 11 | issue = 1–2 | pages = 61–69 | year = 1979 | pmid = 392119 | doi = 10.1080/02791072.1979.10472093 }}</ref> The structure of bufotenine was confirmed in 1934 by ]'s laboratory in Munich, and the first reported synthesis of bufotenine was by Toshio Hoshino and Kenya Shimodaira in 1935.<ref>{{cite journal | title = Synthese des Bufotenins und über 3-Methyl-3-β-oxyäthyl-indolenin. Synthesen in der Indol-Gruppe. XIV | journal = Justus Liebig's Annalen der Chemie | volume = 520 | issue = 1 | pages = 19–30 | year = 1935 | doi = 10.1002/jlac.19355200104 | vauthors = Hoshino T, Shimodaira K }}</ref>


==Sources== ==Sources==
===Toads=== ===Toads===
Bufotenin is found in the skin and eggs of several species of toads belonging to the genus '']'', but is most concentrated in the ] (formerly ''Bufo alvarius'', now ''Incilius alvarius''), the only toad species with enough bufotenin for a psychoactive effect. Extracts of ], containing bufotenin and other ] compounds, have been used in some traditional medicines such as ''ch'an su'' (probably derived from '']''), which has been used medicinally for centuries in China.<ref name=davis/>
{{see also|Psychoactive toad}}
Bufotenin is a chemical constituent in the venom and eggs of several species of toads belonging to the ''Bufo'' genus, including ''Bufo alvarius'' and ''Bufo marinus''. Extracts of toad venom, containing bufotenin and other ] compounds, have been used in some traditional medicines such as ''ch’an su'' (probably derived from '']''), which has been used medicinally for centuries in China.<ref name=davis/>


The toad was "recurrently depicted in ] art,"<ref>{{cite journal |author=Kennedy AB |title=Ecce Bufo: The Toad in Nature and in Olmec Iconography |journal=Current Anthropology |volume=23 |pages=273–90 |year=1982 |doi=10.1086/202831}}</ref> 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.<ref name=davis>{{cite journal |author=Davis W, Weil A |year=1992 |title=Identity of a New World Psychoactive Toad |journal=Ancient Mesoamerica |volume=3 |pages=51–9}}</ref> The toad was "recurrently depicted in ] art",<ref>{{cite journal | vauthors = Yao B, Wang L, Wang H, Bao J, Li Q, Yu F, Zhu W, Zhang L, Li W, Gu Z, Fei K, Zhang P, Zhang F, Huang X | display-authors = 6 | title = Seven interferon gamma response genes serve as a prognostic risk signature that correlates with immune infiltration in lung adenocarcinoma | journal = Aging | volume = 13 | issue = 8 | pages = 11381–11410 | date = April 2021 | pmid = 33839701 | doi = 10.1086/202831 | pmc = 8109098 | s2cid = 143698915 }}</ref> 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.<ref name=davis>{{cite journal |vauthors=Davis W, Weil A |year=1992 |title=Identity of a New World Psychoactive Toad |journal=Ancient Mesoamerica |volume=3 |pages=51–9 |doi=10.1017/s0956536100002297|s2cid=162875250 }}</ref>


In addition to bufotenine, ''Bufo'' venoms also contain ]-like ]s, 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,<ref name=hitt>{{cite journal |doi=10.1056/NEJM198606053142320 |author=Hitt M, Ettinger DD |year=1986 |title=Toad toxicity |journal=N Engl J Med |volume=314 |issue=23 |pages=1517–8 |pmid=3702971}}</ref><ref name=ragonesi>{{cite journal |author=Ragonesi DL |year=1990 |title=The boy who was all hopped up |journal=Contemporary Pediatrics |volume=7 |pages=91–4}}</ref><ref name=brubacher>{{cite journal |author=Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS |year=1996 |title=Treatment of toad venom poisoning with digoxin-specific Fab fragments |journal=Chest |volume=110 |issue=5 |pages=1282–8 |doi=10.1378/chest.110.5.1282 |pmid=8915235}}</ref> some of which resulted in death.<ref name=brubacher/><ref name=godwa>{{cite journal |author=Gowda RM, Cohen RA, Khan, IA |year=2003 |title=Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications |journal=Heart |volume=89 |pages=e14 |url=http://heart.bmj.com/cgi/content/abstract/89/4/e14 |doi=10.1136/heart.89.4.e14 |pmid=12639891 |issue=4 |pmc=1769273}}</ref><ref>{{cite book |author=Lever, Christopher |title=The Cane Toad: The History and Ecology of a Successful Colonist |publisher=Westbury Academic & Scientific Publishing |year=2001 |isbn=1-84103-006-6 }}</ref> In addition to bufotenin, ''Bufo'' secretions also contain ]-like ]s, and ingestion of these toxins can be fatal. Ingestion of ''Bufo'' toad poison and eggs by humans has resulted in several reported cases of poisoning,<ref name=hitt>{{cite journal | vauthors = Hitt M, Ettinger DD | title = Toad toxicity | journal = The New England Journal of Medicine | volume = 314 | issue = 23 | pages = 1517–1518 | date = June 1986 | pmid = 3702971 | doi = 10.1056/NEJM198606053142320 }}</ref><ref name=ragonesi>{{cite journal |author=Ragonesi DL |year=1990 |title=The boy who was all hopped up |journal=Contemporary Pediatrics |volume=7 |pages=91–4}}</ref><ref name=brubacher>{{cite journal | vauthors = Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS | title = Treatment of toad toxin poisoning with digoxin-specific Fab fragments | journal = Chest | volume = 110 | issue = 5 | pages = 1282–1288 | date = November 1996 | pmid = 8915235 | doi = 10.1378/chest.110.5.1282 }}</ref> some of which resulted in death. A court case in Spain, involving a physician who dosed people with smoked Mexican Toad poison, one of his customers died after inhaling three doses, instead of the usual of only one, had images of intoxicated with this smoke suffering obvious hypocalcemic hand muscular spasms.<ref name=brubacher/><ref name=godwa>{{cite journal | vauthors = Gowda RM, Cohen RA, Khan IA | title = Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications | journal = Heart | volume = 89 | issue = 4 | pages = 14e–14 | date = April 2003 | pmid = 12639891 | pmc = 1769273 | doi = 10.1136/heart.89.4.e14 }}</ref><ref>{{cite book |author=Lever, Christopher |title=The Cane Toad: The History and Ecology of a Successful Colonist |publisher=Westbury Academic & Scientific Publishing |year=2001 |isbn=978-1-84103-006-7 }}</ref>


Reports in the mid-1990s indicated that bufotenin-containing toad secretions had appeared as a ], supposedly but in fact ''not'' an ],<ref>Rodrigues, R.J. . ehealthstrategies.com
Contemporary reports indicate that bufotenine-containing toad venom has been used as a ]; that is, as an ], ingested orally in the form of ''ch’an su'',<ref name=brubacher/> 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 ]) has resulted in several cases of poisoning and at least one death.<ref name=brubacher/><ref name=cdc>{{cite journal |author=Centers for Disease Control and Prevention (CDC) |year=1995 |title=Deaths associated with a purported aphrodisiac—New York City, February 1993-May 1995 |journal=MMWR Morb Mortal Wkly Rep |volume=44 |issue=46 |pages=853–5, 861 |pmid=7476839 |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00039633.htm}}</ref> 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.<ref> ''].'' Accessed on May 6, 2007.</ref><ref>]</ref> ], founder of the ] and a proponent of recreational use of '']'' venom, published a booklet titled ''Bufo alvarius: The Psychedelic Toad of the Sonoran Desert''<ref name=most>{{cite web |author = Most, A|title = Bufo avlarius: The Psychedelic Toad of the Sonoran Desert | publisher = www.erowid.org Family Guy season 2 episode 14 Lets Go to the Hop. |url=http://www.erowid.org/archive/sonoran_desert_toad/almost.htm |accessdate = 2007-08-12}}</ref><ref> ''Smoky Mountain News.'' Accessed on May 6, 2007</ref> in 1983 which explained how to extract and smoke the secretions.
</ref> ingested orally in the form of '']'',<ref name=brubacher/> or as a psychedelic, by smoking or orally ingesting ''Bufo'' toad secretions or dried ''Bufo'' skins. The use of ''chan'su'' and ''love stone'' (a related toad skin preparation used as an aphrodisiac in the ]) has resulted in several cases of poisoning and at least one death.<ref name=brubacher/><ref name=cdc>{{cite journal | vauthors = ((Centers for Disease Control and Prevention (CDC))) | title = Deaths associated with a purported aphrodisiac--New York City, February 1993-May 1995 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 44 | issue = 46 | pages = 853–5, 861 | date = November 1995 | pmid = 7476839 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/00039633.htm }}</ref> The practice of orally ingesting toad poison has been referred to in popular culture and in the scientific literature as toad licking and has drawn media attention.<ref> ''].'' Accessed on May 6, 2007.</ref><ref>]</ref> Albert Most, founder of the defunct ] and a proponent of spiritual use of '']'' toxin, published a booklet in 1983 titled ''Bufo alvarius: The Psychedelic Toad of the Sonoran Desert''<ref name=most>{{cite web |author=Most, A |title=Bufo avlarius: The Psychedelic Toad of the Sonoran Desert |publisher=erowid.org |url=http://www.erowid.org/archive/sonoran_desert_toad/almost.htm |access-date=2007-08-12}}</ref><ref> {{webarchive |url=https://web.archive.org/web/20110928055000/http://www.smokymountainnews.com/issues/11_06/11_01_06/out_naturalist.html |date=September 28, 2011 }} ''Smoky Mountain News.'' Accessed on May 6, 2007</ref> which explained how to extract and smoke the secretions.


Bufotenin is also present in the skin secretion of three arboreal amphibian species of the '']'' genus ('']'', '']'', and '']'') from the ] and Atlantic ].<ref name=costa>{{cite journal |author=Costa TO, Morales RA, Brito JP, Gordo M, Pinto AC, Bloch C Jr. |year=2005 |title=Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae) |journal=Toxicon |volume=46 |issue=4 |pages=371–5 |pmid=16054186 |doi=10.1016/j.toxicon.2005.02.006}}</ref> Bufotenin is also present in the skin secretion of three arboreal hylid frogs of the genus '']'' ('']'', '']'', and '']'') from the ] and Atlantic ].<ref name=costa>{{cite journal | vauthors = Costa TO, Morales RA, Brito JP, Gordo M, Pinto AC, Bloch C | title = Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae) | journal = Toxicon | volume = 46 | issue = 4 | pages = 371–375 | date = September 2005 | pmid = 16054186 | doi = 10.1016/j.toxicon.2005.02.006 | bibcode = 2005Txcn...46..371C | url = http://www.alice.cnptia.embrapa.br/alice/handle/doc/186052 }}</ref>


===''Anadenanthera'' seeds=== ===''Anadenanthera'' seeds===
]
Bufotenin is a constituent of the ] of '']'' and '']'' trees. Anadenanthera seeds have been used as an ingredient in psychedelic ] preparations by indigenous cultures of Central and South America.<ref name="ISBN-0789026422">{{cite book |author=Repke, David B.; Torres, Constantino Manuel |title=Anadenanthera: visionary plant of ancient South America |publisher=Haworth Herbal Press |location=New York |year=2006 |isbn=0-7890-2642-2 }}</ref>


Bufotenin is a constituent of the ] of '']'' and '']'' trees. Anadenanthera seeds have been used as an ingredient in psychedelic ] preparations by indigenous cultures of the Caribbean, Central and South America since pre-Columbian times.<ref name="ISBN 0789026422">{{cite book | vauthors = Repke DB, Torres CM |title=Anadenanthera: visionary plant of ancient South America |publisher=Haworth Herbal Press |location=New York |year=2006 |isbn=978-0-7890-2642-2}}</ref><ref name=":0">{{Cite journal| vauthors = Pochettino ML, Cortella AR, Ruiz M |date=1999|title=Hallucinogenic Snuff from Northwestern Argentina: Microscopical Identification of Anadenanthera colubrina var. cebil (Fabaceae) in Powdered Archaeological Material|journal=Economic Botany|volume=53|issue=2|pages=127–132|issn=0013-0001|jstor=4256172|doi=10.1007/BF02866491|bibcode=1999EcBot..53..127P |s2cid=13153575|url=http://sedici.unlp.edu.ar/handle/10915/139078 }}</ref><ref>{{cite journal | vauthors = Miller MJ, Albarracin-Jordan J, Moore C, Capriles JM | title = Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 23 | pages = 11207–11212 | date = June 2019 | pmid = 31061128 | pmc = 6561276 | doi = 10.1073/pnas.1902174116 | bibcode = 2019PNAS..11611207M | doi-access = free }}</ref> The oldest archaeological evidence of use of ''Anadenanthera'' beans is over 4,000 years old.<ref name=":0" />
===Mushrooms===
Bufotenine is also found in several species of ] mushrooms, including '']'' (disputed), '']'', and '']''.<ref name=chilton/>


===Other sources=== ===Other sources===
Bufotenin has been identified as a component in the latex of the takini (''] acutifolium'') tree, which is used as a psychedelic by South American shamans,<ref name=gaillard>{{cite journal |author=Moretti C, Gaillard Y, Grenand P, Bévalot F, Prévosto JM |year=2006 |title=Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic potion used in the Guiana Plateau |journal=J Ethnopharmacol |volume=106 |issue=2 |pages=198–202 |doi=10.1016/j.jep.2005.12.022 |pmid=16455218}}</ref> and in the seeds of '']'' <ref name=chamakura>{{cite journal |author=Chamakura RP |year=1994 |title=Bufotenine—a hallucinogen in ancient snuff powders of South America and a drug of abuse on the streets of New York City |journal=Forensic Sci Rev |volume=6 |issue=1 |pages=2–18}}</ref> Bufotenin has been identified as a component in the latex of the takini (''] acutifolium'') tree, which is used as a psychedelic by South American shamans,<ref name=gaillard>{{cite journal | vauthors = Moretti C, Gaillard Y, Grenand P, Bévalot F, Prévosto JM | title = Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic potion used in the Guiana Plateau | journal = Journal of Ethnopharmacology | volume = 106 | issue = 2 | pages = 198–202 | date = June 2006 | pmid = 16455218 | doi = 10.1016/j.jep.2005.12.022 }}</ref> and in the seeds of '']''.<ref name=chamakura>{{cite journal |author=Chamakura RP |year=1994 |title=Bufotenine—a hallucinogen in ancient snuff powders of South America and a drug of abuse on the streets of New York City |journal=Forensic Sci Rev. |volume=6 |issue=1 |pages=2–18}}</ref> Bufotenin has also been identified in ''],'' '']'', ''A. porphyria'', and ''A. tomentella''.<ref name="Rumack">{{cite book |vauthors=Rumack BH, Spoerke DG |year=1994 |url=https://books.google.com/books?id=WPWsZNvOqVAC |title=Handbook of Mushroom Poisoning: Diagnosis and Treatment |publisher=] |isbn=978-0849301940 |pages=208}}</ref><ref>{{Cite journal |last=Buck |first=Robert W. |date=1963-08-24 |title=Toxicity of Amanita muscaria |url=https://doi.org/10.1001/jama.1963.03060080059020 |journal=JAMA |volume=185 |issue=8 |pages=663–664 |doi=10.1001/jama.1963.03060080059020 |pmid=14016551 |issn=0098-7484}}</ref>

===Humans===
Bufotenin occurs in trace amounts in the human body.<ref name="BarkerMcIlhennyStrassman2012" /><ref name="NeumannDheinKirchhefer2024" /><ref name="KärkkäinenForsströmTornaeus2005" /><ref name="JiménezBouso2022" /> It can be biosynthesized from ] by ] (INMT) ]s.<ref name="BarkerMcIlhennyStrassman2012" /><ref name="JiménezBouso2022">{{cite journal | vauthors = Jiménez JH, Bouso JC | title = Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate | journal = J Psychopharmacol | volume = 36 | issue = 8 | pages = 905–919 | date = August 2022 | pmid = 35695604 | doi = 10.1177/02698811221104054 | url = }}</ref>

====Association with schizophrenia and other mental disorders====
A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects;<ref name="nature_2204">{{cite journal | vauthors = Faurbye A, Pind K | title = Occurrence of bufotenin in the urine of schizophrenic patients and normal persons | journal = Nature | volume = 220 | issue = 5166 | pages = 489 | date = November 1968 | pmid = 5686166 | doi = 10.1038/220489a0 | s2cid = 4192320 | bibcode = 1968Natur.220..489F | doi-access = free }}</ref> however, subsequent research failed to confirm these findings until 2010.<ref name="pm5860629">{{cite journal | vauthors = Siegel M | title = 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 | journal = Journal of Psychiatric Research | volume = 3 | issue = 3 | pages = 205–211 | date = October 1965 | pmid = 5860629 | doi = 10.1016/0022-3956(65)90030-0 }}</ref><ref name=pomilio>{{cite journal | vauthors = Pomilio AB, Vitale AA, Ciprian-Ollivier J, Cetkovich-Bakmas M, Gómez R, Vázquez G | title = Ayahoasca: an experimental psychosis that mirrors the transmethylation hypothesis of schizophrenia | journal = Journal of Ethnopharmacology | volume = 65 | issue = 1 | pages = 29–51 | date = April 1999 | pmid = 10350367 | doi = 10.1016/S0378-8741(98)00163-9 }}</ref><ref name=ciprian>{{cite journal | vauthors = Ciprian-Ollivier J, Cetkovich-Bakmas MG | title = Altered consciousness states and endogenous psychoses: a common molecular pathway? | journal = Schizophrenia Research | volume = 28 | issue = 2–3 | pages = 257–265 | date = December 1997 | pmid = 9468359 | doi = 10.1016/S0920-9964(97)00116-3 | s2cid = 20830063 }}</ref><ref name=carpenter>{{cite journal | vauthors = Carpenter WT, Fink EB, Narasimhachari N, Himwich HE | title = A test of the transmethylation hypothesis in acute schizophrenic patients | journal = The American Journal of Psychiatry | volume = 132 | issue = 10 | pages = 1067–1071 | date = October 1975 | pmid = 1058643 | doi = 10.1176/ajp.132.10.1067 }}</ref><ref name="pm20150873" />

Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders,<ref name="pm8747157">{{cite journal | vauthors = Takeda N, Ikeda R, Ohba K, Kondo M | title = Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders | journal = NeuroReport | volume = 6 | issue = 17 | pages = 2378–2380 | date = November 1995 | pmid = 8747157 | doi = 10.1097/00001756-199511270-00024 }}</ref> such as infant autistic patients.<ref name="pm7749594">{{cite journal | vauthors = Takeda N | title = Serotonin-degradative pathways in the toad (Bufo bufo japonicus) brain: clues to the pharmacological analysis of human psychiatric disorders | journal = Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology| volume = 107 | issue = 2 | pages = 275–281 | date = February 1994 | pmid = 7749594 | doi = 10.1016/1367-8280(94)90051-5 }}</ref> 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.<ref name="pm6147728">{{cite journal | vauthors = Räisänen MJ, Virkkunen M, Huttunen MO, Furman B, Kärkkäinen J | title = Increased urinary excretion of bufotenin by violent offenders with paranoid symptoms and family violence | journal = Lancet | volume = 2 | issue = 8404 | pages = 700–701 | date = September 1984 | pmid = 6147728 | doi = 10.1016/S0140-6736(84)91263-7 | s2cid = 33258299 }}</ref>

A 2010 study utilized a ] 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.<ref name="pm20150873">{{cite journal | vauthors = Emanuele E, Colombo R, Martinelli V, Brondino N, Marini M, Boso M, Barale F, Politi P | display-authors = 6 | title = Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia | journal = Neuro Endocrinology Letters | volume = 31 | issue = 1 | pages = 117–121 | year = 2010 | pmid = 20150873 }}</ref>


==Pharmacology== ==Pharmacology==
{{Primary sources|date=May 2019}}
===Uptake and elimination===
In rats, ]ly administered bufotenin (1–100 μg/kg) distributes mainly to the ], ], and ], and to a much lesser extent, the ] (], ], ], and ]) and ]. It reaches peak concentrations at 1 hour and is nearly completely eliminated within 8 hours.<ref name=fuller>{{cite journal |author=Fuller RW, Snoddy HD, Perry KW |year=1995 |title=Psilocin Tissue distribution, metabolism and effects of bufotenine administered to rats |journal=Neuropharmacology |volume=34 |issue=7 |pages=799–804 |doi=10.1016/0028-3908(95)00049-C |pmid=8532147}}</ref> In humans, ] administration of bufotenin results in ] of (70%) of injected drug in the form of ], an ] ] of serotonin, while roughly 4% is eliminated unmetabolized in the urine. Orally administered bufotenine undergoes extensive ] by the enzyme ].


===Lethal dose=== ===Pharmacodynamics===
Bufotenin is an ] of the ] ].<ref name="McBride2000">{{cite journal | vauthors = McBride MC | title = Bufotenine: toward an understanding of possible psychoactive mechanisms | journal = J Psychoactive Drugs | volume = 32 | issue = 3 | pages = 321–331 | date = 2000 | pmid = 11061684 | doi = 10.1080/02791072.2000.10400456 | url = }}</ref><ref name="PlazasFaraone2023" /> Similarly to serotonin and related compounds like ] (DMT), bufotenin is a ] ] of the serotonin ] and ]s.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /> It is also known to bind with high ] to other ]s, including the serotonin ], ], ], and ]s, and is likely to be a serotonin ] agonist.<ref name="NeumannDheinKirchhefer2024">{{cite journal | vauthors = Neumann J, Dhein S, Kirchhefer U, Hofmann B, Gergs U | title = Effects of hallucinogenic drugs on the human heart | journal = Front Pharmacol | volume = 15 | issue = | pages = 1334218 | date = 2024 | pmid = 38370480 | pmc = 10869618 | doi = 10.3389/fphar.2024.1334218 | doi-access = free | url = }}</ref><ref name="PlazasFaraone2023">{{cite journal | vauthors = Plazas E, Faraone N | title = Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents | journal = Biomedicines | volume = 11 | issue = 2 | date = February 2023 | page = 461 | pmid = 36830997 | pmc = 9953455 | doi = 10.3390/biomedicines11020461 | doi-access = free | url = }}</ref> In addition to its serotonin receptor agonism, bufotenin is a potent ] with an {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} value of 30.5{{nbsp}}nM.<ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology (Berl) | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 | url = }}</ref>
The acute toxicity ({{LD50}}) of bufotenin in rodents has been estimated at 200 to 300&nbsp;mg/kg. Death occurs by respiratory arrest.<ref name="ISBN-0789026422">Anadenanthera: Visionary Plant Of Ancient South America By Constantino Manuel Torres, David B. Repke, 2006, ISBN 0789026422</ref>


Bufotenin has greatly reduced capacity to cross the ] due to its relatively high ] and hence shows prominent ].<ref name="McBride2000" /> As a result, bufotenin has a much greater ratio of ] activity to central effect.<ref name="McBride2000" /> Studies in humans and animals have found a relative lack of ] effects with bufotenin.<ref name="McBride2000" /> However, other studies in humans have reported that the compound can produce psychedelic effects.<ref name="ShenJiangWinter2010">{{cite journal | vauthors = Shen HW, Jiang XL, Winter JC, Yu AM | title = Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions | journal = Curr Drug Metab | volume = 11 | issue = 8 | pages = 659–666 | date = October 2010 | pmid = 20942780 | pmc = 3028383 | doi = 10.2174/138920010794233495 | url = }}</ref><ref name="Ott2001" /> In any case, bufotenin has often been reported to produce pronounced peripheral ] effects.<ref name="McBride2000" /><ref name="NeumannDheinKirchhefer2024" /> These have included ], ], and other effects, among them increased ], chest heaviness, purpling of the head and neck skin (intense ]), ], ], and ].<ref name="McBride2000" /><ref name="NeumannDheinKirchhefer2024" /> It is possible that in addition to its limited central permeation, the peripheral effects of bufotenin have served to mask its central and hallucinogenic effects.<ref name="McBride2000" />
===Effects in humans===
====Fabing & Hawkins (1955)====
In 1955, Fabing and Hawkins administered bufotenin intravenously at doses of up to 16&nbsp;mg to prison inmates at Ohio State Penitentiary.<ref name=fabing>{{cite journal |author=Fabing HD, Hawkins, JR|year = 1956|title = Intravenous bufotenine injection in the human being |journal = Science |volume=123|issue = 3203 |pages=886–7 |doi=10.1126/science.123.3203.886 |pmid=13324106}}</ref> A troubling toxic blood circulation effect causing a purpling of the face was seen in these tests.


In contrast to peripheral administration, ] of bufotenin in animals produces robust psychedelic-like behavioral effects similar to those of other serotonergic psychedelics like ].<ref name="McBride2000" /> In addition, 5-MeO-DMT, the ''O''-] analogue of bufotenin, which has much greater ], is readily able to cross the blood–brain barrier and produce psychedelic effects.<ref name="McBride2000" /> Bufotenin ] ]s, with greater lipophilicity than bufotenin itself, like ] and ], have also shown psychedelic-like effects in animals.<ref name="McBride2000" /><ref name="GlennonGessnerGodse1979">{{cite journal | vauthors = Glennon RA, Gessner PK, Godse DD, Kline BJ | title = Bufotenine esters | journal = J Med Chem | volume = 22 | issue = 11 | pages = 1414–1416 | date = November 1979 | pmid = 533890 | doi = 10.1021/jm00197a025 | url = }}</ref><ref name="GessnerDankova1975">{{cite journal | vauthors = Gessner PK, Dankova J | title = Brain bufotenine from administered acetylbufotenine: Comparison of its tremorgenic activity with that of N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine | date = 1975 | journal = Pharmacologist | volume = 17 | issue = | page = 259 | url = https://bibliography.maps.org/bibliography/default/citation/11230}}</ref>
A subject given 1&nbsp;mg reported “a tight feeling in the chest” and prickling “as if he had been jabbed by needles.” This was accompanied by a “fleeting sensation of pain in both thighs and a mild nausea.” <ref name=fabing/>


] (4-hydroxy-''N'',''N''-dimethyltryptamine) is a ] of bufotenin and might be expected to have similarly limited lipophilicity and blood–brain permeability.<ref name="McBride2000" /> However, psilocin appears to form a ] wherein its ] and ] interact through ].<ref name="McBride2000" /><ref name="PlazasFaraone2023" /> This in turn results in psilocin being much less ], more lipophilic, and more able to cross the blood–brain barrier and exert central actions than it would be otherwise.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /> In contrast, bufotenin is not able to achieve this pseudo-ring system.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /> Accordingly, the experimentally observed ] of psilocin and 5-MeO-DMT have been reported to both be 3.30, whereas that of bufotenin was reported to be 0.06.<ref name="McBride2000" /> A minimum partition coefficient of 1.40 has been proposed for hallucinogenic effects '']'' and an optimal value of 3.14 has been suggested.<ref name="McBride2000" /> In any case, bufotenin does still appear to show minor central permeability and some capacity for psychoactive effects.<ref name="McBride2000" /><ref name="PlazasFaraone2023" />
Another subject given 2&nbsp;mg reported “tightness in his throat”. He had tightness in the stomach, tingling in pretibial areas, and developed a purplish hue in the face indicating blood circulation problems. He vomited after 3 minutes.<ref name=fabing/>


====Effects in humans====
Another subject given 4&nbsp;mg complained of “chest oppression” and that “a load is pressing down from above and my body feels heavy.” The subject also reported “numbness of the entire body” and “a pleasant Martini feeling-my body is taking charge of my mind”. The subject reported he saw red spots passing before his eyes and red-purple spots on the floor, and the floor seemed very close to his face. Within 2 minutes these visual effects were gone, and replaced by a yellow haze, as if he were looking through a lens filter.<ref name=fabing/>
=====Fabing & Hawkins (1955)=====
In 1955, Fabing and Hawkins administered bufotenin intravenously at doses of up to 16&nbsp;mg to prison inmates at ].<ref name=fabing>{{cite journal | vauthors = Fabing HD, Hawkins JR | title = Intravenous bufotenine injection in the human being | journal = Science | volume = 123 | issue = 3203 | pages = 886–887 | date = May 1956 | pmid = 13324106 | doi = 10.1126/science.123.3203.886 | bibcode = 1956Sci...123..886F }}</ref> A toxic effect causing purpling of the face was seen in these tests.


A subject given 1&nbsp;mg reported "a tight feeling in the chest" and prickling "as if he had been jabbed by needles." This was accompanied by a "fleeting sensation of pain in both thighs and a mild nausea."<ref name=fabing/>
Fabing and Hawkins commented that bufotenin’s psychedelic effects were "reminiscent of ] and ] but develop and disappear more quickly, indicating rapid central action and rapid degradation of the drug".


Another subject given 2&nbsp;mg reported "tightness in his throat." He had tightness in the stomach, tingling in pretibial areas, and developed a purplish hue in the face indicating blood circulation problems. He vomited after 3 minutes.<ref name=fabing/>
====Isbell (1956)====
In 1956, Dr. Harris S. Isbell at the Public Health Service Hospital in ] experimented with bufotenine as a snuff. He reported “no subjective or objective effects were observed after spraying with as much as 40 mg bufotenine”; however subjects who received 10–12&nbsp;mg injected ]ly reported “elements of visual hallucinations consisting of a play of colors, lights, and patterns”.<ref name=chilton/>


Another subject given 4&nbsp;mg complained of "chest oppression" and that "a load is pressing down from above and my body feels heavy." The subject also reported "numbness of the entire body" and "a pleasant Martini feeling-my body is taking charge of my mind." The subject reported he saw red spots passing before his eyes and red-purple spots on the floor, and the floor seemed very close to his face. Within 2 minutes these visual effects were gone, and replaced by a yellow haze, as if he were looking through a lens filter.<ref name=fabing/>
====Turner & Merlis (1959)====
Turner and Merlis (1959) <ref name=turner>{{cite journal |author=Turner WJ, Merlis S |year=1959 |title=Effects of some indolealkylamines on man |journal=Arch Neurol Psychiatr |volume=81 |pages=121–9}}</ref> experimented with intravenous administration of bufotenine (as the water soluble creatinine sulfate salt) to schizophrenics at a New York state hospital. They reported that when one subject received 10&nbsp;mg during a 50-second interval, “the peripheral nervous system effects were extreme: at 17 seconds, flushing of the face, at 22 seconds, maximal inhalation, followed by maximal hyperventilation for about 2 minutes, during which the patient was unresponsive to stimuli; her face was plum-colored". Finally, Turner and Merlis reported that:
:“on one occasion, which essentially terminated our study, a patient who received 40 mg intramuscularly, suddenly developed an extremely rapid heart rate; no pulse could be obtained; no blood pressure measured. There seemed to have been an onset of auricular fibrillation…extreme ] developed. Massage over the heart was vigorously executed and the pulse returned to normal…shortly thereafter the patient, still cyanotic, sat up saying: ‘Take that away. I don’t like them’.”


Fabing and Hawkins commented that bufotenin's psychedelic effects were "reminiscent of ] and ] but develop and disappear more quickly, indicating rapid central action and rapid degradation of the drug".{{citation needed|date=October 2021}}
After pushing doses to the morally admissible limit without producing visuals, Turner and Merlis conservatively concluded: “We must reject bufotenine…as capable of producing the acute phase of ] intoxication”.<ref name=chilton/>


====McLeod and Sitaram (1985)==== =====Isbell (1956)=====
In 1956, ] at the ] in ], experimented with bufotenin as a ]. He reported "no subjective or objective effects were observed after spraying with as much as 40 mg bufotenine"; however, subjects who received 10–12&nbsp;mg by ] injection reported "elements of visual hallucinations consisting of a play of colors, lights, and patterns."<ref name=chilton/>
A 1985 study by McLeod and Sitaram in humans reported that bufotenine administered ] at a dose of 1–16&nbsp;mg had no effect, other than intense local irritation. When given intravenously at low doses (2–4&nbsp;mg), bufotenine ] caused anxiety but no other effects; however, a dose of 8&nbsp;mg resulted in profound emotional and perceptual changes, involving extreme ], a sense of imminent death, and visual disturbance associated with color reversal and distortion, and intense flushing of the cheeks and forehead.<ref name=mcleod>{{cite journal |author=McLeod WR, Sitaram BR |year=1985 |title=Bufotenine reconsidered |journal=] |volume=72 |issue=5 |pages=447–50 |doi=10.1111/j.1600-0447.1985.tb02638.x}}</ref>


====Ott (2001)==== =====Turner & Merlis (1959)=====
Turner and Merlis (1959)<ref name=turner>{{cite journal | vauthors = Turner WJ, Merlis S | title = Effect of some indolealkylamines on man | journal = A.M.A. Archives of Neurology and Psychiatry | volume = 81 | issue = 1 | pages = 121–129 | date = January 1959 | pmid = 13605329 | doi = 10.1001/archneurpsyc.1959.02340130141020 }}</ref> experimented with intravenous administration of bufotenin (as the water-soluble creatinine sulfate salt) to schizophrenics at a New York state hospital. They reported that when one subject received 10&nbsp;mg during a 50-second interval, "the ] effects were extreme: at 17 seconds, ] of the face, at 22 seconds, maximal inhalation, followed by maximal ] for about 2 minutes, during which the patient was unresponsive to stimuli; her face was plum-colored." Finally, Turner and Merlis reported:
In 2001, ethnobotanist ] published the results of a study in which he self-administered free base bufotenine via ] (5–100&nbsp;mg), ]ly (50&nbsp;mg), ] (30&nbsp;mg), ] (100&nbsp;mg) and via ] (2–8&nbsp;mg).<ref name=ott2>{{cite journal |author=Ott J |year=2001 |title=Pharmanopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine |journal=J Psychoactive Drugs |volume=33 |issue=4 |pages=403–7 |url=http://entheology.org/edoto/anmviewer.asp?a=9&z=8 |pmid=11824699}}</ref> Ott reported “visionary effects" of intranasal bufotenine and that the "visionary threshold dose" by this route was 40&nbsp;mg, with smaller doses eliciting perceptibly psychoactive effects. He reported that "intranasal bufotenine is throughout quite physically relaxing; in no case was there facial rubescence, nor any discomfort nor disesteeming side effects".

{{blockquote|on one occasion, which essentially terminated our study, a patient who received 40 mg intramuscularly, suddenly developed an extremely ]; no pulse could be obtained; no blood pressure measured. There seemed to have been an onset of ] . . . extreme ] developed. Massage over the heart was vigorously executed and the pulse returned to normal . . . shortly thereafter the patient, still cyanotic, sat up saying: "Take that away. I don't like them."}}

After pushing doses to the morally admissible limit without producing visuals, Turner and Merlis conservatively concluded: "We must reject bufotenine . . . as capable of producing the acute phase of ] intoxication."<ref name=chilton/>

=====McLeod and Sitaram (1985)=====
A 1985 study by McLeod and Sitaram in humans reported that bufotenin administered ] at a dose of 1–16&nbsp;mg had no effect, other than intense local irritation. When given intravenously at low doses (2–4&nbsp;mg), bufotenin ] caused anxiety but no other effects; however, a dose of 8&nbsp;mg resulted in profound emotional and perceptual changes, involving extreme ], a sense of imminent death, and visual disturbance associated with color reversal and distortion, and intense flushing of the cheeks and forehead.<ref name=mcleod>{{cite journal | vauthors = McLeod WR, Sitaram BR | title = Bufotenine reconsidered | journal = Acta Psychiatrica Scandinavica | volume = 72 | issue = 5 | pages = 447–450 | date = November 1985 | pmid = 4091027 | doi = 10.1111/j.1600-0447.1985.tb02638.x | s2cid = 9578617 }}</ref>

=====Ott (2001)=====
In 2001, ethnobotanist ] published the results of a study in which he self-administered ] bufotenin via ] (5–100&nbsp;mg), ]ly (50&nbsp;mg), ] (30&nbsp;mg), ] (100&nbsp;mg) and via ] (2–8&nbsp;mg).<ref name="Ott2001">{{cite journal | vauthors = Ott J | title = Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine | journal = Journal of Psychoactive Drugs | volume = 33 | issue = 3 | pages = 273–281 | year = 2001 | pmid = 11718320 | doi = 10.1080/02791072.2001.10400574 | s2cid = 5877023 }}</ref> Ott reported "visionary effects" of intranasal bufotenin and that the "visionary threshold dose" by this route was 40&nbsp;mg, with smaller doses eliciting perceptibly psychoactive effects. He reported that "intranasal bufotenine is throughout quite physically relaxing; in no case was there facial rubescence, nor any discomfort nor disesteeming side effects".


At 100&nbsp;mg, effects began within 5 minutes, peaked at 35–40 minutes, and lasted up to 90 minutes. Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque". At 100&nbsp;mg, effects began within 5 minutes, peaked at 35–40 minutes, and lasted up to 90 minutes. Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque".
Free base bufotenin taken sublingually was found to be identical to intranasal use. The potency, duration, and psychedelic action was the same. Ott found vaporized free base bufotenin active from 2–8&nbsp;mg with 8&nbsp;mg producing "ring-like, swirling, colored patterns with eyes closed". He noted that the visionary effects of insufflated bufotenine were verified by one colleague, and those of vaporized bufotenine by several volunteers. Free base bufotenin taken sublingually was found to be identical to intranasal use. The potency, duration, and psychedelic action was the same. Ott found vaporized free base bufotenin active from 2–8&nbsp;mg with 8&nbsp;mg producing "ring-like, swirling, colored patterns with eyes closed". He noted that the visual effects of insufflated bufotenin were verified by one colleague, and those of vaporized bufotenin by several volunteers.


Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of ] without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered intravenously. Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of ] without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered intravenously.


====Lethal dose====
===Association with schizophrenia and other mental disorders===
The acute toxicity ({{LD50}}) of bufotenin in rodents has been estimated at 200 to 300&nbsp;mg/kg. Death occurs by respiratory arrest.<ref name="ISBN 0789026422"/> In April 2017, a South Korean man died of bufotenin poisoning after consuming ] that had been mistaken for edible ],<ref>{{cite news | title = South Korean man dies after eating toads | date = 21 April 2017 | work = BBC | url = https://www.bbc.com/news/world-asia-39665192}}</ref> while in Dec. 2019, five Taiwanese men became ill and one man died after eating ] that they mistook for frogs.<ref>{{Cite web|url=https://www.taiwannews.com.tw/en/news/3839159|title=Taiwanese dies from eating toads, 5 injured|website=Taiwan News|date=17 December 2019|access-date=2019-12-18}}</ref>
A study conducted in the late 1960s reported the detection of bufotenin in the urine of schizophrenic subjects;<ref name="nature_2204">] |volume=28 |issue=2-3 |pages=257–65 |pmid=9468359 |doi=10.1016/S0920-9964(97)00116-3 }}</ref><ref name=carpenter>{{cite journal |author=Carpenter WT Jr, Fink EB, Narasimhachari N, Himwich HE |year=1975 |title=A test of the transmethylation hypothesis in acute schizophrenic patients |journal=Am J Psychiatry |volume=132 |issue=10 |pages=1067–71 |pmid=1058643 }}</ref>


===Pharmacokinetics===
Studies have detected endogenous bufotenin in urine specimens from individuals with other psychiatric disorders,<ref name="pm8747157">{{cite journal |author=Takeda N, Ikeda R, Ohba K, Kondo M |title=Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders |journal=Neuroreport |volume=6 |issue=17 |pages=2378–80 |year=1995 |month=November |pmid=8747157 |doi=10.1097/00001756-199511270-00024 }}</ref> such as infant autistic patients.<ref name="pm7749594">{{cite journal |author=Takeda N |title=Serotonin-degradative pathways in the toad (''Bufo bufo japonicus'') brain: clues to the pharmacological analysis of human psychiatric disorders |journal=Comp Biochem Physiol Pharmacol Toxicol Endocrinol |volume=107 |issue=2 |pages=275–81 |year=1994 |month=February |pmid=7749594 |doi=10.1016/1367-8280(94)90051-5 }}</ref> 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.<ref name="pm6147728">{{cite journal |author=Räisänen MJ, Virkkunen M, Huttunen MO, Furman B, Kärkkäinen J |title=Increased urinary excretion of bufotenin by violent offenders with paranoid symptoms and family violence |journal=Lancet |volume=2 |issue=8404 |pages=700–1 |year=1984 |month=September |pmid=6147728 |doi=10.1016/S0140-6736(84)91263-7 }}</ref>
Bufotenin has been reported to undergo a strong ]<ref name="NeumannDheinKirchhefer2024" /> and to not be ].<ref name="McBride2000" /> This is in contrast to its ] ], which is thought to form a ] that limits its susceptibility to ] by ] (MAO).<ref name="McBride2000" /> However, bufotenin actually does show oral activity if sufficiently high doses are taken.<ref name="NeumannDheinKirchhefer2024" /> About 10-fold higher doses of bufotenin seem to be required orally compared to ]ly for effects.<ref name="NeumannDheinKirchhefer2024" />


In rats, ]ly administered bufotenin (1–100 μg/kg) distributes mainly to the ], ], and ], and to a much lesser extent, the ] (], ], ], and ]), and ]. It reaches peak concentrations at one hour and is nearly eliminated within 8 hours.<ref name=fuller>{{cite journal | vauthors = Fuller RW, Snoddy HD, Perry KW | title = Tissue distribution, metabolism and effects of bufotenine administered to rats | journal = Neuropharmacology | volume = 34 | issue = 7 | pages = 799–804 | date = July 1995 | pmid = 8532147 | doi = 10.1016/0028-3908(95)00049-C | s2cid = 23801665 }}</ref> In humans, ] administration of bufotenin results in ] of (70%) of injected drug in the form of ], an ] ] of serotonin, while roughly 4% is eliminated unmetabolized in the urine. Orally administered bufotenin undergoes extensive ] by the enzyme ].
A 2010 study utilized a ] 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.<ref name="pm20150873">{{cite journal |author=Emanuele E, Colombo R, Martinelli V, Brondino N, Marini M, Boso M, Barale F, Politi P |title=Elevated urine levels of bufotenine in patients with autistic spectrum disorders and schizophrenia. |journal=Neuro Endocrinol Lett |volume=31 |issue=1 |pages=117–21 |year=2010 |pmid=20150873}}</ref>

==Chemistry==
Bufotenin, also known as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a ] and a ] of ] (DMT; ''N'',''N''-dimethyltryptamine) and ] (5-hydroxytryptamine; 5-HT).

The predicted ] of bufotenin ranges from 0.89 to 2.04.<ref name="PubChem">{{cite web | title=Bufotenine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/10257 | access-date=11 September 2024}}</ref><ref name="DrugBank">{{cite web | title=Bufotenine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=31 July 2007 | url=https://go.drugbank.com/drugs/DB01445 | access-date=12 September 2024}}</ref><ref name="ChemSpider">{{cite web | title=BUFOTENINE | website=ChemSpider | date=12 September 2024 | url=https://www.chemspider.com/Chemical-Structure.9839.html | access-date=12 September 2024}}</ref> For comparison, the predicted log P of DMT is 2.06 to 2.5<ref name="PubChem-DMT">{{cite web | title=Dimethyltryptamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/6089 | access-date=11 September 2024}}</ref><ref name="DrugBank-DMT">{{cite web | title=Dimethyltryptamine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=31 July 2007 | url=https://go.drugbank.com/drugs/DB01488 | access-date=12 September 2024}}</ref><ref name="ChemSpider-DMT">{{cite web | title=Dimethyltryptamine | website=ChemSpider | date=12 September 2024 | url=https://www.chemspider.com/Chemical-Structure.5864.html | access-date=12 September 2024}}</ref> and of serotonin is 0.2 to 0.56.<ref name="PubChem-5-HT">{{cite web | title=Serotonin | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5202 | access-date=11 September 2024}}</ref><ref name="DrugBank-5-HT">{{cite web | title=Serotonin: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=21 February 2013 | url=https://go.drugbank.com/drugs/DB08839 | access-date=12 September 2024}}</ref><ref name="ChemSpider-5-HT">{{cite web | title=Serotonin | website=ChemSpider | date=12 September 2024 | url=https://www.chemspider.com/Chemical-Structure.5013.html | access-date=12 September 2024}}</ref>

===Analogues and derivatives===
Some ]s and ]s of bufotenin (5-HO-DMT), aside from serotonin and DMT, include ] (4-HO-DMT) (a positional isomer), ] (''O''-methylbufotenin), ], ], ] (''N''-methylbufotenin), ], and ], among others.


==Legal status== ==Legal status==
===Australia===
Bufotenine is regulated as a ] drug (ID number 7403) by the ].<ref name=dea/> It is classified as a Schedule I controlled substance according to the Criminal Code Regulations of the Government of the Commonwealth of Australia.<ref name=ccr>{{cite journal|author = |title=Criminal Code Regulation 2005 (SL2005-2) | version = | publisher = Australian Capital Territory | date = May 1, 2005 |url=http://www.legislation.act.gov.au/sl/2005-2/20050501-18968/rtf/2005-2.rtf | format = rtf | accessdate = 2007-08-12}}</ref>
Bufotenin is classified as a Schedule I controlled substance according to the Criminal Code Regulations of the Government of the Commonwealth of Australia.<ref name=ccr>{{citation |title=Criminal Code Regulation 2005 (SL2005-2) |publisher=Australian Capital Territory |date=May 1, 2005 |url=http://www.legislation.act.gov.au/sl/2005-2/20050501-18968/rtf/2005-2.rtf |format=rtf |access-date=2007-08-12}}</ref> It is also listed as a Schedule 9 substance under the ] (October 2015).<ref name="Poisons Standard">Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534</ref> A schedule 9 drug is outlined in the ] as "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of the CEO."<ref> {{Webarchive|url=https://web.archive.org/web/20151222191725/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A26063P/%24FILE/Poisons%20Act%201964%20-%20%5B09-f0-04%5D.pdf?OpenElement |date=2015-12-22 }}. slp.wa.gov.au</ref>

Under the ] {{convert|6.0|g|oz}} is determined to be enough for court of trial and {{convert|2.0|g|oz}} is considered intent to sell and supply.<ref> {{Webarchive|url=https://web.archive.org/web/20151222180141/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A28280P/%24FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement |date=2015-12-22 }}. slp.wa.gov.au</ref>

===United Kingdom===
In the United Kingdom, bufotenin is a Class A drug under the 1971 ].


===United States===
In the UK, the substance is a Class A drug under the 1971 Misuse of Drugs Act, although numerous shops sell ''Amanita Muscaria'' across the Internet. Although some people claim that they may contain the substance, it is often considered an area of dispute.
Bufotenin (DEA Drug Code 7403) is regulated as a ] drug by the ] at the federal level in the ] and is therefore illegal to buy, possess, and sell.<ref name="PART 1308 — SCHEDULES OF CONTROLLED SUBSTANCES - 1308.11 Schedule I"> {{Webarchive|url=https://web.archive.org/web/20090827043725/http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |date=2009-08-27 }} deadiversion.usdoj.gov</ref>


==See also== ===Sweden===
Sweden's public health agency suggested classifying Bufotenin as a hazardous substance, on May 15, 2019.<ref>{{cite web | url=https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2019/maj/folkhalsomyndigheten-foreslar-att-20-amnen-klassas-som-narkotika-eller-halsofarlig-vara/ | title=Folkhälsomyndigheten föreslår att 20 ämnen klassas som narkotika eller hälsofarlig vara | publisher=Folkhälsomyndigheten | language=sv | date=15 May 2019 | access-date=11 November 2019 | archive-date=20 October 2021 | archive-url=https://web.archive.org/web/20211020121058/https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2019/maj/folkhalsomyndigheten-foreslar-att-20-amnen-klassas-som-narkotika-eller-halsofarlig-vara/ | url-status=dead }}</ref>


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==References== == References ==
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{{TiHKAL}}
{{Hallucinogenic tryptamines}}
{{Serotonergics}}
{{Tryptamines}}
{{Neurotransmitters}} {{Neurotransmitters}}
{{Hallucinogens}}
{{Serotonin receptor modulators}}
{{Monoamine releasing agents}}
{{Tryptamines}}


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