View source for Bufotenin

{{Short description|Psychedelic drug found in toads, mushrooms and plants}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = verified
| verifiedrevid = 443669819
| image = Bufotenin2DACS.svg
| image_class = skin-invert-image
| width = 200px
| image2 = Bufotenin-3d-sticks.png
| image_class2 = bg-transparent
| width2 = 200px

<!--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 [[Sweden]]
| routes_of_administration = [[Oral administration|Oral]], [[intranasal administration|intranasal]]/[[insufflation]], [[inhalational administration|inhalation]], [[sublingual administration|sublingual]], [[rectal administration|rectal]], [[intravenous injection|intravenous]]<ref name="Ott2001a" />
| class = [[Serotonergic psychedelic]]; [[Hallucinogen]]; [[Serotonin receptor agonist]]; [[Serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[agonist]]

<!--Pharmacokinetic data-->
| bioavailability = Weakly active (with or without {{Abbrlink|MAOI|monoamine oxidase inhibitor}})<ref name="Ott2001b" /><ref name="Ott2001a" />
| protein_bound = 
| metabolism = [[Deamination]] via {{Abbrlink|MAO-A|monoamine oxidase A}} and [[conjugation (biochemistry)|conjugation]] ([[glucuronidation]], [[sulfation]])<ref name="ShenJiangWinter2010" /><ref name="PlazasFaraone2023" />
| metabolites = • {{Abbrlink|5-HIAA|5-Hydroxyindoleacetic acid}}<ref name="ShenJiangWinter2010" /><br />• [[Glucuronide]] and [[sulfate]] [[conjugation (biochemistry)|conjugate]]s<ref name="ShenJiangWinter2010" />
| onset = {{Abbrlink|PO|Oral administration}}: 20{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|IN|Intranasal administration}}: 5–15{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|SL|Sublingual administration}}: 5–15{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|REC|Rectal administration}}: ~15{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|INH|Inhalational administration}}: ≤1–2{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|IV|Intravenous injection}}: <1{{nbsp}}min<ref name="FabingHawkins1956" />
| elimination_half-life = 
| duration_of_action = {{Abbrlink|PO|Oral administration}}: ~2{{nbsp}}hours<ref name="Ott2001a" /><br />{{Abbrlink|IN|Intranasal administration}}: 30–90{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><ref name="MorrisOtt2023" /><br />{{Abbrlink|SL|Sublingual administration}}: 30–90{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|REC|Rectal administration}}: ~1{{nbsp}}hour<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|INH|Inhalational administration}}: 60–90{{nbsp}}min<ref name="Ott2001b" /><ref name="Ott2001a" /><br />{{Abbrlink|IV|Intravenous injection}}: ~5–120{{nbsp}}min<ref name="Ott2001b" />
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| 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 = 9839
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0A31347TZK
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08299
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 3210
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| 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

<!--Chemical data-->
| IUPAC_name = 3-[2-(Dimethylamino)ethyl]-1''H''-indol-5-ol
| C=12 | H=16 | N=2 | O=1
| SMILES = CN(C)CCc1c[nH]c2ccc(O)cc12
| 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

<!-- Physical data -->
| melting_point = 146
| melting_high = 147
| boiling_point = 320
}}

'''Bufotenin''', also known as '''dimethylserotonin''' or as '''5-hydroxy-''N'',''N''-dimethyltryptamine''' ('''5-HO-DMT'''), is a [[serotonergic psychedelic]] of the [[substituted tryptamine|tryptamine]] family. It is a [[chemical derivative|derivative]] of the psychedelic [[dimethyltryptamine]] (DMT) and of the [[neurotransmitter]] [[serotonin]] (5-hydroxytryptamine; 5-HT). The compound is an [[alkaloid]] found in some species of [[mushroom]]s, [[plants]], and [[psychoactive toad|toad]]s. It is also found [[natural product|naturally]] 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, for instance derived from the trees ''[[Anadenanthera colubrina]]'' and ''[[Anadenanthera peregrina]]'', has a long history of [[entheogen]]ic use as a [[hallucinogenic snuff|snuff]] in [[South America]].<ref name="Ott2001a" /><ref name="MorrisOtt2023" /><ref name="Morris2022" /><ref name="TittarelliMannocchiPantano2015">{{cite journal | vauthors = Tittarelli R, Mannocchi G, Pantano F, Romolo FS | title = Recreational use, analysis and toxicity of tryptamines | journal = Curr Neuropharmacol | volume = 13 | issue = 1 | pages = 26–46 | date = January 2015 | pmid = 26074742 | pmc = 4462041 | doi = 10.2174/1570159X13666141210222409 | url = }}</ref>

The name bufotenin originates from the toad genus ''[[Bufo]]'', which includes several species of [[psychoactive toad]]s, most notably ''[[Incilius alvarius]]'' (formerly ''Bufo alvarius''), that [[secrete]] [[bufotoxin]]s from their [[parotoid gland]]s.<ref>[http://amphibiaweb.org/cgi/amphib_query?query_src=aw_lists_soundInclude_&where-genus=Bufo&where-species=alvarius Bufo Alvarius.] ''AmphibiaWeb.'' Accessed on May 6, 2007.</ref> However, ''Bufo'' and related species like ''Incilius alvarius'' contain only trace amounts of bufotenin, with their major active component instead being [[5-MeO-DMT]]. In addition to DMT and serotonin, bufotenin is similar in [[chemical structure]] to other psychedelics such as 5-MeO-DMT and [[psilocin]] (4-HO-DMT). These compounds also occur in some of the same fungus, plant, and animal species as bufotenin.

Bufotenin acts as a [[potency (pharmacology)|potent]] and [[binding selectivity|non-selective]] [[serotonin receptor agonist]], including of the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub>]], [[5-HT2A receptor|5-HT<sub>2A</sub>]], [[5-HT2C receptor|5-HT<sub>2C</sub>]], and [[5-HT3 receptor|5-HT<sub>3</sub> receptor]]s, among others.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /><ref name="NeumannDheinKirchhefer2024" /><ref name="BloughLandavazoDecker2014" /> It also acts as a potent and specific [[serotonin releasing agent]].<ref name="BloughLandavazoDecker2014" /> The compound is more [[hydrophilic]] than other related tryptamines and consequently is more [[peripherally selective drug|peripherally selective]].<ref name="McBride2000" /><ref name="GumpperNichols2024" /> In relation to this, bufotenin has been associated with prominent [[peripheral nervous system|peripheral]] serotonergic [[side effect]]s, such as [[cardiovascular]] changes.<ref name="McBride2000" /><ref name="NeumannDheinKirchhefer2024" /><ref name="TiHKAL" /> The cardiovascular effects of bufotenin can be powerful and potentially dangerous.<ref name="Waser1967">{{cite book | vauthors=Holmstedt B, Daly JW, Del Pozo EC, Horning EC, Isbel H, Szara S | chapter=Discussion on the Psychoactive Action of Various Tryptamine Derivatives | title=Ethnopharmacologic Search for Psychoactive Drugs | publisher=Raven Press | date=1967 | isbn=978-0-89004-047-8 | chapter-url=https://books.google.com/books?id=IvfBDethZkYC&pg=PA419 | pages=374–382 (377) | quote = [DR. ISBELL:] It has been said that bufotenine is not a psychotomimetic drug. I don't think we should say that. The difficulty is that bufotenine is a drug that has extremely powerful and dangerous cardiovascular effects, and for that reason it is not possible to push the dose in man. Also, it would be difficult to differentiate whether psychotic reactions were due to central effects or to cardiovascular actions. Cardiovascular actions include hypertension and development of an arrhythmia which actually amounts to a ventricular standstill. The auricle does not beat, the beat drops out, and the ventricle takes over, and it is very frightening. Simultaneously with the hypertension and ventricular escapes, one sees spectacular cynanosis in the upper part of the body, similar to that which has been described in the carcinoid flush, which is presumably due to serotonin. So bufotenine is a difficult drug to work in man for this reason, and it would not be too surprising if it did not have some kind of a central action if it were possible to extract it out.}}</ref>

For many decades and even into the present, bufotenin has been considered by many experts, such as [[David E. Nichols]], to be either inactive or only weakly active as a psychedelic in humans and to produce robust [[toxicity|toxic]] effects.<ref name="GumpperNichols2024">{{cite journal | vauthors = Gumpper RH, Nichols DE | title = Chemistry/structural biology of psychedelic drugs and their receptor(s) | journal = Br J Pharmacol | volume = | issue = | date = October 2024 | article-number = bph.17361 | pmid = 39354889 | doi = 10.1111/bph.17361 | url = | quote = The weaker pKa of psilocin relative to bufotenine means that psilocin is less highly ionized at pH 7.4—that is, 8.5% free base versus 0.53% for bufotenine at pH 7.4. Ionized amines must be unionized and desolvated to cross the blood–brain barrier; the intramolecular H bond in psilocin compensates for that as reflected by the higher lipophilicity of psilocin relative to bufotenine. [...] This would explain why bufotenine is still an agonist at the 5-HT2A receptor but due to its poor physiochemical properties is not psychoactive in humans. }}</ref><ref name="Ott2001b">{{cite book | vauthors = [[Jonathan Ott|Ott J]] | chapter=Shamanic-Snuff Psychonautica: Pharmañopo: Bufotenine—Psychonautics | pages=99–116 (105–112, 114–115) | title=Shamanic Snuffs or Entheogenic Errhines | publisher=Entheobotanica | year=2001 | isbn=978-1-888755-02-2 | oclc=56061312 | url=https://books.google.com/books?id=AUP7NwAACAAJ | chapter-url=https://archive.org/details/vdocuments.mx_unknown-55b347d139b58/page/n51/mode/1up | access-date=24 January 2025 }}</ref><ref name="McBride2000" /><ref name="ShenJiangWinter2010" /> [[Alexander Shulgin]] was also uncertain whether bufotenin was an active psychedelic.<ref name="TiHKAL">{{cite book | vauthors = Shulgin AT, Shulgin A | url = http://www.erowid.org/library/books_online/tihkal/tihkal19.shtml | title = TiHKAL: The Continuation | date = 1997 | publisher = Transform Press | isbn = 9780963009692 | edition = 1st | location = Berkeley, CA | oclc = 38503252 | quote = And so it is with bufotenine. Is it an active psychedelic? Absolutely yes, absolutely no, and maybe yes and maybe no. [...] Some clinicians demand that the compound is unquestionably a psychotomimetic and it must be catalogued right up there along with LSD and psilocybin. Others, equally sincere, present human trials that suggest only peripheral toxicity and conclude that there is no central action to be seen. And there are many who state that there are no effects for it at all, either inside or outside the CNS. The psychopharmacological status of bufotenine, like that of Uri Geller, may be essentially unanswerable. [...] A second report carries, at least for me, much more impact. A study of the use of the seeds of a South American legume, Anadenanthera colubrina var. Cebil by the Argentine Shamans in Chaco Central, shows then to be dramatically psychedelic. And yet, extremely sophisticated spectroscopic analysis has shown them to contain bufotenine and only bufotenine as their alkaloid component. At the bottom line, I do not really know of bufotenine is a psychedelic drug. Maybe yes and maybe no. }}</ref><ref name="Shulgin2003">{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025 | quote=For a number of reasons, some pharmacological and some political, the compound 5-hydroxy-N,N-dimethyltryptamine, bufotenine, deserves special comment. From the pharmacological point of view, the compound is clearly active, but the nature of this activity is difficult to classify. The early studies that report effects in humans followed intravenous administration, and the responses noted (anxiety, panic, visual distortion, intense flushing) have been ascribed to extreme cardiovascular action and possible increases in interocular pressure. No effects have been observed following intranasal or oral administration. Recent studies with snuffs from roasted red seeds of the South American trees of the Anadenanthera species have proved highly active and yet careful analysis have shown that the only alkaloid present was bufotenine. Yet there are several reports in the medical literature of human studies where the compound is reported to be without activity.}}</ref><ref name="MorrisOtt2023" /> However, [[Jonathan Ott]] found in 2001 via [[self-experimentation]] that bufotenin is in fact a potent psychedelic and does not necessarily produce serious adverse effects.<ref name="ShenJiangWinter2010" /><ref name="MorrisOtt2023" /><ref name="Ott2001b" /><ref name="Ott2001a" /> [[Hamilton Morris]] has further supported these findings with his own self-experimentation, although bufotenin was reported to be strongly [[nausea|nauseating]] for himself and many others.<ref name="Morris2022">{{cite web | title=A New One-Hour Talk On 5-MeO-DMT | website=[[Hamilton Morris#Podcast|The Hamilton Morris Podcast]] | publisher=Patreon | host=[[Hamilton Morris]] | date=1 December 2022 | url=https://www.patreon.com/posts/new-one-hour-on-75373519 | access-date=21 January 2025 | time=6:27–8:40, 10:15–11:13 | quote=[Morris:] Bufotenine is a drug that I have tried. I've tried isolated pure bufotenine and it is a psychedelic that is both pharmacologically and experientially and chemically intermediate between DMT and 5-MeO-DMT. So it has a longer duration than actually both 5-MeO-DMT and DMT. It's yet less visual than DMT but more visual than 5-MeO-DMT, so it's kind of like in-between the two. It's also very nauseating, which is the main reason that people seem not to enjoy it very much. But it is a classical psychedelic drug that produces visionary effects. And Jonathan Ott actually liked the effect of it quite a bit. }}</ref><ref name="MorrisOtt2023">{{cite podcast | url=https://www.patreon.com/posts/podcast-28-talk-55653035 | title=PODCAST 28: A talk with Jonathan Ott | website=[[Hamilton Morris#Podcast|The Hamilton Morris Podcast]] | publisher=Patreon | host=[[Hamilton Morris]] | date=1 September 2021 | time=49:20–50:36 | access-date=20 January 2025 | quote=[Morris:] I've used [bufotenine] a couple times, once at 50 milligrams of the freebase snorted. [...] I found it to be extremely nauseating. I found it to be qualitatively intermediate between 5-MeO-DMT and DMT in that it was more visual than my experiences with 5-MeO-DMT but less visual than my typical experiences with DMT. It had a longer duration than 5-MeO-DMT and maybe even a longer duration than DMT as well. It was about an hour. Although I don't have all that much experience snorting DMT freebase. }}</ref> According to Morris, the psychedelic effects of bufotenin are like a cross between those of DMT and 5-MeO-DMT.<ref name="Morris2022" /><ref name="MorrisOtt2023" /> Morris has stated that bufotenin may in fact be the psychedelic with the longest history of human entheogenic use.<ref name="Morris2022" /><ref name="MorrisOtt2023" /> Bufotenin has also been encountered as a [[recreational drug]] in forensic samples, for instance in [[New York City]].<ref name="Chamakura1994" />

==Use and effects==
{{Primary sources section|date=May 2019}}

===Fabing & Hawkins (1955)===
In 1955, Fabing and Hawkins administered bufotenin [[intravenous injection|intravenously]] at doses of up to 16{{nbsp}}mg to prison inmates at [[Ohio State Penitentiary]].<ref name="FabingHawkins1956">{{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="FabingHawkins1956" />

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="FabingHawkins1956" />

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="FabingHawkins1956" />

Fabing and Hawkins commented that bufotenin's psychedelic effects were "reminiscent of <nowiki>[</nowiki>[[LSD]]<nowiki>]</nowiki> and [[mescaline]] but develop and disappear more quickly, indicating rapid central action and rapid degradation of the drug".<ref name="FabingHawkins1956" />

===Isbell (1956)===
In 1956, [[Harris Isbell]] at the [[Public Health Service Hospital]] in [[Lexington, Kentucky]], experimented with bufotenin as a [[hallucinogenic snuff|snuff]] made from ''[[Anadenanthera peregrina]]''.<ref name="HolmstedtLindgren1967" /> 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 [[intramuscular]] injection reported "elements of visual hallucinations consisting of a play of colors, lights, and patterns."<ref name="ChiltonBigwoodJensen1979" /><ref name="TurnerMerlis1959" /><ref name="HolmstedtLindgren1967">{{cite book | vauthors=Holmstedt B, Lindgren JE | chapter = Chemical Constituents and Pharmacology of South American Snuffs | pages = 339–373 | veditors=Efron DH, Holmstedt B, Kline NS | title=Ethnopharmacologic Search for Psychoactive Drugs, Proceedings of a Symposium held in San Francisco, California, January 28-30, 1967 | publisher=Raven Press | date=1967 | isbn=978-0-89004-047-8 | oclc = 14498182 | url = https://books.google.com/books?id=UeZsAAAAMAAJ | chapter-url = https://archive.org/details/ethnopharmacolog00efro_0/page/339/mode/1up | quote = In a letter, Dr. Harris Isbell describes his experiment with the same compounds in the following way: "We studied several forms of the material: Untreated snuff, roasted snuff, limed and roasted snuff, fermented snuff, fermented and limed snuff, fermented, limed and roasted snuff. Our subjects inhaled the snuff through straws. We obtained no reports that there were any subjective effects after inhalation of this material in amounts ranging up to 1 gram, and we further were unable to obtain any evidence of objective effects on pupillary size, tendon reflexes, body temperature, respiration, blood pressure etc., after doses ranging up to 1 gram orally. Inhalation of pure bufotenine in aerosol suspension, or oral ingestion of bufotenine in doses running up to 100 mg (total dose) also were without effect." The above quoted experiments were all performed with snuff made from the sample of Piptadenia peregrina in which Horning et al. had found 5-OH-DMT (bufotenine) to be the main component, and this fully explains the negative results.}}</ref>

===Turner & Merlis (1959)===
Turner and Merlis (1959)<ref name="TurnerMerlis1959">{{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 [[peripheral nervous system]] effects were extreme: at 17 seconds, [[flushing (physiology)|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:

{{blockquote|on one occasion, which essentially terminated our study, a patient who received 40 mg intramuscularly, suddenly developed an extremely [[tachycardia|rapid heart rate]]; no pulse could be obtained; no blood pressure measured. There seemed to have been an onset of [[auricular fibrillation]] . . . extreme [[cyanosis]] 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 [[Cohoba]] intoxication."<ref name="ChiltonBigwoodJensen1979" />

===Hofmann (1963)===
[[Albert Hofmann]] tried bufotenin [[oral administration|orally]] at doses of up to 50{{nbsp}}mg but experienced no psychoactive effects.<ref name="Hofmann1963">{{cite journal | vauthors = Hofmann A | title = Psychotomimetic Substances | journal = The Indian Journal of Pharmacy | date = August 1963 | volume = 25 | issue = 8 | pages = 245–256 | url = https://bibliography.maps.org/resources/download/11101 | archive-url = https://web.archive.org/web/20250407130544/https://bibliography.maps.org/resources/download/11101 | archive-date = 7 April 2025 | quote = Bufotenin, which was first discovered in the skin glands of toads34, has a similar activity to dimethyltryptamne35 when administered by intravenous injection. Other investigators found no hallucinogenic activity after i.v. injections up to 20 mg.35 In personal experiments by the writer doses up to 50 mg. bufotenin taken perorally did not produce any psychic effects17. [...] It could be that the special application of these substances in the form of a snuff powder modifies in some way their psychic activity. [...] 17. Hofmann, A. Unpublished results.}}</ref><ref name="Ott2001a" />

===McLeod and Sitaram (1985)===
A 1985 study by McLeod and Sitaram in humans reported that bufotenin administered [[Insufflation (medicine)|intranasally]] at a dose of 1–16{{nbsp}}mg had no effect, other than intense local irritation. When given [[intravenous injection|intravenously]] at low doses (2–4{{nbsp}}mg), bufotenin [[oxalate]] caused anxiety but no other effects; however, a dose of 8{{nbsp}}mg resulted in profound emotional and perceptual changes, involving extreme [[anxiety]], a sense of imminent death, and visual disturbance associated with color reversal and distortion, and intense flushing of the cheeks and forehead.<ref name="McLeodSitaram1985">{{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>

===Shulgin (1997)===
[[Alexander Shulgin]] reviewed the literature on bufotenin in his book ''[[TiHKAL]]''.<ref name="TiHKAL" /> However, he and his collaborators did not appear to try it themselves.<ref name="TiHKAL" />

===Ott (2001)===
In 2001, ethnobotanist [[Jonathan Ott]] published the results of a study in which he [[self-administration|self-administered]] [[free base]] bufotenin via [[insufflation (medicine)|insufflation]] (5–100{{nbsp}}mg), [[sublingual administration|sublingually]] (50{{nbsp}}mg), [[rectal administration|rectally]] (30{{nbsp}}mg), [[oral administration|orally]] (100{{nbsp}}mg) and via [[smoking|vaporization]] (2–8{{nbsp}}mg).<ref name="Ott2001b" /><ref name="Ott2001a">{{cite journal | vauthors = [[Jonathan Ott|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.<ref name="Ott2001a" /> He reported that "intranasal bufotenine is throughout quite physically relaxing; in no case was there facial rubescence, nor any discomfort nor disesteeming side effects".<ref name="Ott2001b" /><ref name="Ott2001a" />

At 100{{nbsp}}mg, effects began within 5{{nbsp}}minutes, peaked at 35 to 40{{nbsp}}minutes, and lasted up to 90{{nbsp}}minutes.<ref name="Ott2001b" /><ref name="Ott2001a" /> Higher doses produced effects that were described as psychedelic, such as "swirling, colored patterns typical of tryptamines, tending toward the arabesque".<ref name="Ott2001b" /><ref name="Ott2001a" /> Free base bufotenin taken sublingually was found to be identical to intranasal use.<ref name="Ott2001b" /><ref name="Ott2001a" /> The potency, duration, and psychedelic action was the same.<ref name="Ott2001b" /><ref name="Ott2001a" /> Ott found vaporized free base bufotenin active from 2 to 8{{nbsp}}mg with 8{{nbsp}}mg producing "ring-like, swirling, colored patterns with eyes closed".<ref name="Ott2001b" /><ref name="Ott2001a" /> He noted that the visual effects of insufflated bufotenin were verified by one colleague, and those of vaporized bufotenin by several volunteers.<ref name="Ott2001b" /><ref name="Ott2001a" />

Ott concluded that free base bufotenin taken intranasally and sublingually produced effects similar to those of [[Yopo]] without the toxic peripheral symptoms, such as facial flushing, observed in other studies in which the drug was administered [[intravenous injection|intravenously]].<ref name="Ott2001b" /><ref name="Ott2001a" />

===Morris (2020s)===
[[Hamilton Morris]], a [[psychoactive drug]] [[journalist]], the creator of ''[[Hamilton's Pharmacopeia]]'', and a [[pharmacologist]], has experimented with bufotenin and found that it was an active psychedelic.<ref name="Morris2022" /><ref name="MorrisOtt2023" /> He has claimed that its effects are like a cross between those of DMT and 5-MeO-DMT, being less visual than DMT but more visual than 5-MeO-DMT.<ref name="Morris2022" /><ref name="MorrisOtt2023" /> Morris has also stated that bufotenin is very [[nausea|nauseating]] and this has made it unpleasant for himself and other people.<ref name="Morris2022" /><ref name="MorrisOtt2023" /> By [[insufflation]], he has said that its [[duration of action|duration]] is about 1{{nbsp}}hour and is longer than that of DMT or 5-MeO-DMT.<ref name="Morris2022" /><ref name="MorrisOtt2023" />

Morris and others have suggested use of the [[serotonin]] [[5-HT3 receptor|5-HT<sub>3</sub> receptor]] [[receptor antagonist|antagonist]] [[ondansetron]] (Zofran) to prevent nausea and vomiting with especially nauseating or serotonin 5-HT<sub>3</sub> receptor agonistic serotonergic psychedelics like bufotenin.<ref name="RossiHallakBousoSaiz2022">{{cite journal | vauthors = Rossi GN, Hallak JE, Bouso Saiz JC, Dos Santos RG | title = Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges | journal = Expert Opinion on Drug Safety | volume = 21 | issue = 6 | pages = 761–776 | date = June 2022 | pmid = 35426754 | doi = 10.1080/14740338.2022.2066650 }}</ref><ref name="GlennonDukat2023" /><ref name="Morris2023">{{cite podcast | url=https://www.patreon.com/posts/december-q-doi-5-95470096 | title=December Q&A: DOI prohibition, 5-HT3 antagonists, prodrugs and more! | website=[[Hamilton Morris#Podcast|The Hamilton Morris Podcast]] | publisher=Patreon | host=[[Hamilton Morris]] | date=28 December 2023 | time= | access-date=17 February 2025 | quote= }}</ref>

==Side effects==
[[Side effect]]s of bufotenin include [[nausea]] and [[vomiting]], among others.<ref name="Ott2001b" /><ref name="Ott2001a" /><ref name="MorrisOtt2023" /><ref name="Morris2022" /> It can also produce powerful and potentially dangerous and frightening [[cardiovascular]] [[side effect]]s at doses that allow for hallucinogenic effects.<ref name="Waser1967" />

==Overdose==
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="RepkeTorres2006" /> In April 2017, a South Korean man died after consuming bufotenin-containing [[Asiatic toad|toad]]s that had been mistaken for edible [[Chinese edible frog|Asian bullfrogs]],<ref name="BBC2017">{{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 bufotenin-containing [[Bufo bankorensis|Central Formosa toads]] 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>

==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Activities of bufotenin}}
|-
! [[Biological target|Target]] !! [[Affinity (pharmacology)|Affinity]] (K<sub>i</sub>, nM)
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 2.5–1,023 (K<sub>i</sub>)<br />13–366 ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}})<br />95% ({{Abbrlink|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT1B receptor|5-HT<sub>1B</sub>]] || 41–912
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 3.7–29
|-
| [[5-HT1E receptor|5-HT<sub>1E</sub>]] || {{Abbr|ND|No data}}
|-
| [[5-HT1F receptor|5-HT<sub>1F</sub>]] || 31.6
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 15–>10,000 (K<sub>i</sub>)<br />3.49–232 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />83–100% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT2B receptor|5-HT<sub>2B</sub>]] || 630
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 16–145
|-
| [[5-HT3 receptor|5-HT<sub>3</sub>]] || 34–210
|-
| [[5-HT4 receptor|5-HT<sub>4</sub>]] || {{Abbr|ND|No data}} (K<sub>i</sub>)<br />191–1,590 ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}})<br />71% ({{Abbr|E<sub>max</sub>|maximal efficacy}})
|-
| [[5-HT5A receptor|5-HT<sub>5A</sub>]] || 1,000–2,900
|-
| [[5-HT5B receptor|5-HT<sub>5B</sub>]] || 1,585
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 4.5–112
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 7.9–95
|-
| {{Abbrlink|SERT|Serotonin transporter}} || 1,200 ({{Abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}})<br />30.5 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|-
| {{Abbrlink|NET|Norepinephrine transporter}} || >10,000 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|-
| {{Abbrlink|DAT|Dopamine transporter}} || >10,000 ({{Abbr|EC<sub>50</sub>|Half-maximal effective concentration}})
|- class="sortbottom"
| colspan="2" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. Proteins are animal or human. '''Refs:''' <ref name="PDSPKiDatabase">{{cite web | title=PDSP Database | website=UNC | url=https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=bufotenine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | language=zu | access-date=22 January 2025}}</ref><ref name="BindingDB">{{cite web | vauthors = Liu J | title=BindingDB BDBM50024206 3-[2-(dimethylamino)ethyl]-1H-indol-5-ol::3-[2-(dimethylamino)ethyl]-5-indolol::3-[2-(dimethylamino)ethyl]indol-5-ol::3-[beta-(dimethylamino)ethyl]-5-hydroxyindole::5-hydroxy-N,N-dimethyltryptamine::Bufotenin::Bufotenine::CHEMBL416526::DM5-HT::DMT,5-OH::N,N-dimethylserotonin | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50024206 | access-date=22 January 2025}}</ref><ref name="Glennon1987">{{cite journal | vauthors = Glennon RA | title = Central serotonin receptors as targets for drug research | journal = J Med Chem | volume = 30 | issue = 1 | pages = 1–12 | date = January 1987 | pmid = 3543362 | doi = 10.1021/jm00384a001 | url = | quote = Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites}}</ref><ref name="PlazasFaraone2023" /><ref name="CramervanDrimmelenLong1990" /><ref name="BloughLandavazoDecker2014" /><ref name="ChenLiYu2023a" /><ref name="ChenLiYu2023b" /><ref name="Nelson1991" /><br /><ref name="ColasChoiLaunay1997">{{cite journal | vauthors = Colas JF, Choi DS, Launay JM, Maroteaux L | title = Evolutionary conservation of the 5-HT2B receptors | journal = Ann N Y Acad Sci | volume = 812 | issue = 1| pages = 149–153 | date = May 1997 | pmid = 9186729 | doi = 10.1111/j.1749-6632.1997.tb48157.x | bibcode = 1997NYASA.812..149C | url = https://hal.archives-ouvertes.fr/hal-03721324/file/NYACS9%3A9%3A95%20-%20short.pdf}}</ref><ref name="DumuisAnsanayWaeber1997">{{cite book | vauthors = Dumuis A, Ansanay H, Waeber C, Sebben M, Fagni L, Bockaert J | title=Pharmacochemistry Library | chapter=5-HT4 receptors | publisher=Elsevier | volume=27 | date=1997 | isbn=978-0-444-82041-9 | doi=10.1016/s0165-7208(97)80017-7 | pages=261–308}}</ref><ref name="EganGrindeDupre2000">{{cite journal | vauthors = Egan C, Grinde E, Dupre A, Roth BL, Hake M, Teitler M, Herrick-Davis K | title = Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors | journal = Synapse | volume = 35 | issue = 2 | pages = 144–150 | date = February 2000 | pmid = 10611640 | doi = 10.1002/(SICI)1098-2396(200002)35:2<144::AID-SYN7>3.0.CO;2-K | url = }}</ref><ref name="MedhurstKaumann1993">{{cite journal | vauthors = Medhurst AD, Kaumann AJ | title = Characterization of the 5-HT4 receptor mediating tachycardia in piglet isolated right atrium | journal = Br J Pharmacol | volume = 110 | issue = 3 | pages = 1023–1030 | date = November 1993 | pmid = 8298790 | pmc = 2175817 | doi = 10.1111/j.1476-5381.1993.tb13916.x | url = }}</ref>
|}

Bufotenin is an [[structural analog|analogue]] of the [[monoamine neurotransmitter]] [[serotonin]].<ref name="McBride2000">{{cite journal | vauthors = McBride MC | title = Bufotenine: toward an understanding of possible psychoactive mechanisms | journal = Journal of Psychoactive Drugs | volume = 32 | issue = 3 | pages = 321–331 | date = 2000 | pmid = 11061684 | doi = 10.1080/02791072.2000.10400456 }}</ref><ref name="PlazasFaraone2023" /> Similarly to serotonin and related compounds like [[dimethyltryptamine]] (DMT), bufotenin is an [[agonist]] of the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub>]], [[5-HT2A receptor|5-HT<sub>2A</sub>]], [[5-HT2C receptor|5-HT<sub>2C</sub>]], [[5-HT3 receptor|5-HT<sub>3</sub>]], and [[5-HT4 receptor|5-HT<sub>4</sub> receptor]]s.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /><ref name="BloughLandavazoDecker2014" /><ref name="CramervanDrimmelenLong1990">{{cite journal | vauthors = Cramer W, van Drimmelen M, Long S, Tulp M | title=Bufotenin: actions of 5-HT3 receptors | journal=European Journal of Pharmacology | volume=183 | issue=6 | date=1990 | doi=10.1016/0014-2999(90)93672-D | pages=2148–2149}}</ref><ref name="GlennonPeroutkaDukat1991">{{cite book | vauthors = Glennon RA, Peroutka SJ, Dukat M | title=Serotonin: Molecular Biology, Receptors and Functional Effects | chapter=Binding Characteristics of a Quaternary Amine Analog of Serotonin: 5-HTQ | publisher=Birkhäuser Basel | publication-place=Basel | date=1991 | isbn=978-3-0348-7261-4 | doi=10.1007/978-3-0348-7259-1_17 | pages=186–191}}</ref><ref name="OliviervanWijngaardenSoudijn1997">{{cite book | vauthors = Van Wijngaarden I, Soudijn W | chapter = 5-HT2A, 5-HT2B and 5-HT2C receptor ligands. | veditors = Olivier B, Van Wijngaarden I, Soudijn W | title=Serotonin Receptors and their Ligands | publisher=Elsevier Science | series=Pharmacochemistry Library | year=1997 | isbn=978-0-08-054111-2 | chapter-url=https://books.google.com/books?id=lfo0hGqIex0C&pg=PA161 | access-date=22 January 2025 | page=161}}</ref><ref name="Glennon1987" /> It is also known to bind with high [[affinity (pharmacology)|affinity]] to other [[serotonin receptor]]s, including the serotonin [[5-HT1B receptor|5-HT<sub>1B</sub>]], [[5-HT1D receptor|5-HT<sub>1D</sub>]], [[5-HT1F receptor|5-HT<sub>1F</sub>]], [[5-HT6 receptor|5-HT<sub>6</sub>]], and [[5-HT7 receptor|5-HT<sub>7</sub> receptor]]s.<ref name="CramervanDrimmelenLong1990" /><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 = Frontiers in Pharmacology | volume = 15 | issue = | article-number = 1334218 | date = 2024 | pmid = 38370480 | pmc = 10869618 | doi = 10.3389/fphar.2024.1334218 | doi-access = free }}</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 | page = 461 | date = February 2023 | pmid = 36830997 | pmc = 9953455 | doi = 10.3390/biomedicines11020461 | doi-access = free }}</ref><ref name="OliviervanWijngaardenSoudijn1997" /><ref name="Glennon1987" /> Bufotenin has about 5- to 10-fold higher affinity for the serotonin 5-HT<sub>2A</sub> receptor than [[5-MeO-DMT]], about the same [[receptor activation|activational]] [[potency (pharmacology)|potency]] as 5-MeO-DMT at the receptor ''[[in vitro]]'' ({{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} = 3.49{{nbsp}}nM and 3.87{{nbsp}}nM, respectively), and about 3-fold higher ''[[in-vivo]]'' potency than 5-MeO-DMT when they are in the [[brain]].<ref name="ShenJiangWinter2010" /><ref name="BloughLandavazoDecker2014" /> In contrast to many other psychedelic tryptamines, bufotenin shows high affinity for the serotonin 5-HT<sub>3</sub> receptors, similar to or higher than that of serotonin,<ref name="Dukat2004">{{cite journal | vauthors = Dukat M | title=5-HT3 Serotonin Receptor Agonists: A Pharmacophoric Journey | journal=Current Medicinal Chemistry - Central Nervous System Agents | volume=4 | issue=2 | date=1 June 2004 | issn=1568-0150 | doi=10.2174/1568015043356995 | pages=77–94}}</ref><ref name="CramervanDrimmelenLong1990" /><ref name="GlennonPeroutkaDukat1991" /> and this receptor is strongly associated with production of [[nausea]] and [[vomiting]].<ref name="JohnstonLuRudd2014">{{cite journal | vauthors = Johnston KD, Lu Z, Rudd JA | title = Looking beyond 5-HT(3) receptors: a review of the wider role of serotonin in the pharmacology of nausea and vomiting | journal = European Journal of Pharmacology | volume = 722 | issue = | pages = 13–25 | date = January 2014 | pmid = 24189639 | doi = 10.1016/j.ejphar.2013.10.014 }}</ref><ref name="GlennonDukat2023">{{cite journal | vauthors = Glennon RA, Dukat M | title=Quipazine: Classical hallucinogen? Novel psychedelic? | journal=Australian Journal of Chemistry | volume=76 | issue=5 | date=2 May 2023 | issn=0004-9425 | doi=10.1071/CH22256 | pages=288–298}}</ref> In addition to its serotonin receptor agonism, bufotenin is a potent [[serotonin releasing agent]] (SRA) with an {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} value of 30.5{{nbsp}}nM, whereas it is inactive as a releaser of [[dopamine]] or [[norepinephrine]] ({{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} > 10,000{{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 | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 }}</ref>

A special property of 5-MeO-DMT is that it has much higher affinity for and activational potency at the serotonin 5-HT<sub>1A</sub> receptor compared to other psychedelic tryptamines such as DMT and this is thought to confer it with unique and distinct hallucinogenic effects.<ref name="DourronNicholsSimonsson2023">{{cite journal | vauthors = Dourron HM, Nichols CD, Simonsson O, Bradley M, Carhart-Harris R, Hendricks PS | title = 5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk? | journal = Psychopharmacology (Berl) | volume = 242| issue = 7| pages = 1457–1479| date = December 2023 | pmid = 38072874 | doi = 10.1007/s00213-023-06517-1 | url = }}</ref><ref name="ReckwegUthaugSzabo2022">{{cite journal | vauthors = Reckweg JT, Uthaug MV, Szabo A, Davis AK, Lancelotta R, Mason NL, Ramaekers JG | title = The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) | journal = J Neurochem | volume = 162 | issue = 1 | pages = 128–146 | date = July 2022 | pmid = 35149998 | pmc = 9314805 | doi = 10.1111/jnc.15587 | url = }}</ref><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> Similarly, bufotenin has also shown greatly increased affinity for the serotonin 5-HT<sub>1A</sub> receptor.<ref name="Nelson1991">{{cite journal | vauthors = Nelson DL | title = Structure-activity relationships at 5-HT1A receptors: binding profiles and intrinsic activity | journal = Pharmacol Biochem Behav | volume = 40 | issue = 4 | pages = 1041–1051 | date = December 1991 | pmid = 1816558 | doi = 10.1016/0091-3057(91)90124-k | url = }}</ref> Whereas the serotonin 5-HT<sub>1A</sub> receptor affinities (K<sub>i</sub> or {{Abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}}) of tryptamine and DMT were 125{{nbsp}}nM and 170{{nbsp}}nM, respectively, the affinities of serotonin (5-HO-T), [[5-methoxytryptamine]] (5-MeO-T), bufotenin (5-HO-DMT), and 5-MeO-DMT were 3{{nbsp}}nM, 9{{nbsp}}nM, 4.9{{nbsp}}nM, and 6.5{{nbsp}}nM, respectively.<ref name="Nelson1991" /> Comparing bufotenin to DMT, it had 35-fold higher affinity for the serotonin 5-HT<sub>1A</sub> receptor in comparison.<ref name="Nelson1991" /> Findings were very similar in another study not only in terms of affinities but also activational potencies.<ref name="ChenLiYu2023a">{{cite journal | vauthors = Chen X, Li J, Yu L, Maule F, Chang L, Gallant JA, Press DJ, Raithatha SA, Hagel JM, Facchini PJ | title = A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines | journal = J Biol Chem | volume = 299 | issue = 10 | article-number = 105231 | date = October 2023 | pmid = 37690691 | pmc = 10570959 | doi = 10.1016/j.jbc.2023.105231 | doi-access = free | url = }}</ref><ref name="ChenLiYu2023b">{{cite journal | vauthors = Chen X, Li J, Yu L, Dhananjaya D, Maule F, Cook S, Chang L, Gallant J, Press D, Bains JS, Raithatha S, Hagel J, Facchini P | title=Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery | journal=Research Square | date=10 March 2023 | doi=10.21203/rs.3.rs-2667175/v1 | doi-access=free | url=https://www.researchsquare.com/article/rs-2667175/latest.pdf | access-date=18 March 2025 | page=}}</ref> Bufotenin had a similar {{Abbr|EC<sub>50</sub>|half-maximal effective concentration}} at the serotonin 5-HT<sub>1A</sub> receptor as serotonin, 5-MeO-T, and 5-MeO-DMT (13{{nbsp}}nM, 3{{nbsp}}nM, 14{{nbsp}}nM, and 21{{nbsp}}nM, respectively), and a far greater value than tryptamine or DMT (899{{nbsp}}nM and 1,293{{nbsp}}nM, respectively).<ref name="ChenLiYu2023a" /><ref name="ChenLiYu2023b" />

Bufotenin is thought to have reduced capacity to cross the [[blood–brain barrier]] due to its relatively high [[hydrophilicity]] and hence to show significant [[peripherally selective drug|peripheral selectivity]].<ref name="McBride2000" /> As a result, bufotenin has a greater ratio of [[peripheral nervous system|peripheral]] activity to central effect.<ref name="McBride2000" /> Bufotenin produces the [[head-twitch response]], a behavioral proxy of psychedelic effects, in rodents.<ref name="WieczorekWitkowskaJasicka-Misiak2015">{{cite book | vauthors =  Wieczorek PP, Witkowska D, Jasicka-Misiak I, Poliwoda A, Oterman M, Zielińska K | title=Studies in Natural Products Chemistry | chapter=Bioactive Alkaloids of Hallucinogenic Mushrooms | publisher=Elsevier | volume=46 | date=2015 | isbn=978-0-444-63462-7 | doi=10.1016/b978-0-444-63462-7.00005-1 | pages=133–168 | url=https://www.researchgate.net/publication/274273796}}</ref><ref name="CornePickering1967">{{cite journal | vauthors = Corne SJ, Pickering RW | title = A possible correlation between drug-induced hallucinations in man and a behavioural response in mice | journal = Psychopharmacologia | volume = 11 | issue = 1 | pages = 65–78 | date = 1967 | pmid = 5302272 | doi = 10.1007/BF00401509 | url = }}</ref><ref name="ZhangYangYang2025">{{cite journal | vauthors = Zhang M, Yang Y, Yang Z, Wen X, Zhang C, Xiao P, Wang Y, Sun J, Wang H, Wang X | title = Structural insights into tryptamine psychedelics: The role of hydroxyl indole ring site in 5-HT2A receptor activation and psychedelic-like activity | journal = Eur J Med Chem | volume = 281 | issue = | article-number = 117049 | date = January 2025 | pmid = 39541872 | doi = 10.1016/j.ejmech.2024.117049 | url = }}</ref> However, it requires doses about 10-fold higher than those of psilocybin to produce behavioral responses in rats.<ref name="PlazasFaraone2023" /> Conversely, unlike other psychedelics, bufotenin fails to substitute for [[LSD]], [[psilocybin]], or [[5-MeO-DMT]] in rodent [[drug discrimination]] tests.<ref name="Baker2018">{{cite book | vauthors = Baker LE | title = Behavioral Neurobiology of Psychedelic Drugs | chapter = Hallucinogens in Drug Discrimination | series = Curr Top Behav Neurosci | volume = 36 | pages = 201–219 | date = 2018 | pmid = 28484970 | doi = 10.1007/7854_2017_476 | isbn = 978-3-662-55878-2 | chapter-url = | quote = An example of stimulus generalization (i.e., drug substitution) is depicted in Fig. 1, reprinted from a study reported by Winter et al. (2007). This figure illustrates dose-response curves obtained with LSD, psilocin, DMT, and bufotenine in rats trained to discriminate 0.5 mg/kg psilocybin. LSD and psilocin produced full substitution for psilocybin, whereas DMT produced only 73% psilocybin-appropriate responding and bufotenine produced less than 20% psilocybin-appropriate responding at the doses tested.}}</ref><ref name="HelsleyFiorellaRabin1998">{{cite journal | vauthors = Helsley S, Fiorella D, Rabin RA, Winter JC | title = A comparison of N,N-dimethyltryptamine, harmaline, and selected congeners in rats trained with LSD as a discriminative stimulus | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 22 | issue = 4 | pages = 649–663 | date = May 1998 | pmid = 9682278 | doi = 10.1016/s0278-5846(98)00031-1 | url = }}</ref><ref name="WinterRiceAmorosi2007">{{cite journal | vauthors = Winter JC, Rice KC, Amorosi DJ, Rabin RA | title = Psilocybin-induced stimulus control in the rat | journal = Pharmacol Biochem Behav | volume = 87 | issue = 4 | pages = 472–480 | date = October 2007 | pmid = 17688928 | pmc = 2000343 | doi = 10.1016/j.pbb.2007.06.003 | url = | quote = The failure of bufotenine to mimic psilocybin is in keeping with previous reports in rats in which bufotenine did not substitute for 5-MeO-DMT (Spencer et al., 1987), for LSD (Helsley et al., 1998), or for TVX Q 7821, a 5-HT1A receptor agonist (Spencer and Traber, 1987). The hallucinogenicity of bufotenine has been a matter of controversy for some time (Shulgin and Shulgin, 1997, pages 473–478; Torres and Repke, 2006). Nonetheless, the absence of activity with respect to stimulus activity in the rat as exemplified in Fig. 3 is plausibly explained on the basis of low lipid solubility and an associated inability to cross the blood–brain barrier. While psilocin has a chloroform/water coefficient of 5.52, that of bufotenine is only 0.06 (Gessner et al., 1968). In keeping with a primarily peripheral mechanism in the rat for bufotenine is the observation that the hypothermic effects of bufotenine are antagonized by xylamidine, a peripherally acting 5-HT antagonist (Winter, 1972).}}</ref><ref name="SpencerGlaserTraber1987">{{cite journal | vauthors = Spencer DG, Glaser T, Traber J | title = Serotonin receptor subtype mediation of the interoceptive discriminative stimuli induced by 5-methoxy-N,N-dimethyltryptamine | journal = Psychopharmacology (Berl) | volume = 93 | issue = 2 | pages = 158–166 | date = 1987 | pmid = 3122248 | doi = 10.1007/BF00179927 | url = }}</ref> Relatedly, findings on the effects of bufotenin in animals have been described as "equivocal".<ref name="BrimblecombePinder1975" /> Studies have been similarly mixed on the [[psychedelic drug|psychedelic]] effects of bufotenin in humans, with some finding a relative lack of psychedelic effects and pronounced toxic effects, while others have found psychedelic effects without major adverse effects.<ref name="McBride2000" /><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="Ott2001a" /><ref name="TiHKAL" /> In any case, bufotenin has often been reported to produce pronounced peripheral [[serotonergic drug|serotonergic]] effects.<ref name="McBride2000" /><ref name="NeumannDheinKirchhefer2024" /> These have included [[cardiovascular]], [[gastrointestinal]], and other effects, among them increased [[respiratory rate]], chest heaviness, purpling of the head and neck skin (intense [[skin flushing]]), [[nausea]], [[vomiting]], and [[retching]].<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" /> The adverse effects of bufotenin may be more pronounced with [[intravenous injection]] compared to other routes such as [[insufflation]].<ref name="MorrisOtt2023" />

In contrast to peripheral administration, [[intracerebroventricular injection]] of bufotenin in animals readily produces robust psychedelic-like behavioral effects similar to those of other serotonergic psychedelics like [[5-MeO-DMT]].<ref name="McBride2000" /> In addition, 5-MeO-DMT, the ''O''-[[methyl group|methylated]] analogue of bufotenin, which has greater [[lipophilicity]], is readily able to cross the blood–brain barrier and produce psychedelic effects.<ref name="McBride2000" /> Bufotenin [[prodrug]] [[ester]]s, with greater lipophilicity than bufotenin itself, like [[O-Acetylbufotenine|''O''-acetylbufotenin]] and [[O-Pivalylbufotenine|''O''-pivalylbufotenin]], have also shown robust 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>

===Pharmacokinetics===
Bufotenin has been reported to undergo a strong [[first-pass effect]]<ref name="NeumannDheinKirchhefer2024" /> and to not be [[oral administration|orally active]].<ref name="McBride2000" /> This is in contrast to its [[positional isomer]] [[psilocin]], which is thought to form a [[Ring (chemistry)#Rings and ring systems|pseudo-ring system]] that limits its susceptibility to [[drug metabolism|metabolism]] by [[monoamine oxidase]] (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 [[parenteral administration|parenteral]]ly for effects.<ref name="NeumannDheinKirchhefer2024" />

In rats, [[subcutaneous injection|subcutaneous]]ly administered bufotenin (1–100{{nbsp}}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]].<ref name="ShenJiangWinter2010" /><ref name="FullerSnoddyPerry1995" />  Only very small amounts of bufotenin reach the brain in rats following [[intravenous administration]], which is attributed to its poor [[lipophilicity]] and consequent [[peripherally selective drug|peripheral selectivity]].<ref name="BrimblecombePinder1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 | quote = [...] only very small amounts of bufotenin are found in rat brain following intravenous administration (Vogel, 1969), a finding in keeping with the low lipid solubility of the drug as measured by a chloroform-water coefficient of only 0·06 at physiological pH (Gessner, Godse, Krull, and McMullan, 1968). [...] Animal studies with bufotenin are equally equivocal to those in man. [...]}}</ref><ref name="Vogel1969">{{cite journal | vauthors = Vogel WH | title = Physiological disposition of 5-methoxytryptamine and the rope climbing performance of rats | journal = Psychopharmacologia | volume = 15 | issue = 2 | pages = 88–95 | date = 1969 | pmid = 5351124 | doi = 10.1007/BF00407040 | url = }}</ref><ref name="SandersBush1967">{{cite journal | vauthors = Sanders E, Bush MT | title = Distribution, metabolism and excretion of bufotenine in the rat with preliminary studies of its O-methyl derivative | journal = J Pharmacol Exp Ther | volume = 158 | issue = 2 | pages = 340–352 | date = November 1967 | pmid = 6065154 | doi = 10.1016/S0022-3565(25)27800-4  | url = }}</ref> The [[brain-to-blood ratio]] of [[5-MeO-DMT]] (''O''-methylbufotenin) was 15{{nbsp}}times higher than that of bufotenin in the study.<ref name="SandersBush1967" /> Bufotenin reaches peak circulating concentrations at one hour and is nearly eliminated within 8{{nbsp}}hours.<ref name="FullerSnoddyPerry1995">{{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, [[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 bufotenin undergoes extensive [[first-pass metabolism]] by the enzyme [[monoamine oxidase]].

[[File:Psilocin intramolecular hydrogen bond and pseudo-ring system.png|class=skin-invert-image|thumb|right|300px|Theoretical [[intramolecular force|intramolecular]] [[hydrogen bond]] and [[Ring (chemistry)#Rings and ring systems|pseudo-ring system]] occurring with [[psilocin]] (4-HO-DMT) but not with bufotenin (5-HO-DMT).<ref name="GumpperNichols2024" /><ref name="McBride2000" />]]

[[Psilocin]] (4-HO-DMT) is a [[positional isomer]] of bufotenin and might be expected to have similarly limited lipophilicity and blood–brain permeability.<ref>{{cite journal | vauthors = Gumpper RH, Nichols DE | title = Chemistry/structural biology of psychedelic drugs and their receptor(s) | journal = Br J Pharmacol | volume = | issue = | date = October 2024 | article-number = bph.17361 | pmid = 39354889 | doi = 10.1111/bph.17361 | url = | quote = In contrast to DMT, psilocybin is orally active. [...] A structurally related molecule, [5-HO-DMT], known as bufotenine, is inactive after oral administration. How does the simple transposition of the hydroxy from the 4 to the 5 position alter the physicochemical properties of the DMT core? We asked that question more than four decades ago. In a study by Migliaccio et al. (1981), the 360 MHz proton NMR, the amine pKa values and the octanol–water Log P values were determined experimentally and compared for both psilocin and bufotenine (Figure 3a). The side chain protons in the NMR for bufotenine were shown to be rapidly rotating with no preference for gauche or trans conformations, whereas the side chain for psilocin was less mobile and was determined to favour a gauche (80%) versus trans (20%) conformation. Because psilocin is a weaker base but is also more lipid soluble, it was proposed that psilocin formed an intramolecular hydrogen bond, as illustrated in Figure 3a. In the energy-minimized structure of this conformation, the length of the hydrogen bond is 1.88 Å. The weaker pKa of psilocin relative to bufotenine means that psilocin is less highly ionized at pH 7.4—that is, 8.5% free base versus 0.53% for bufotenine at pH 7.4. Ionized amines must be unionized and desolvated to cross the blood–brain barrier; the intramolecular H bond in psilocin compensates for that as reflected by the higher lipophilicity of psilocin relative to bufotenine. Finally, the mechanism of deamination by MAO involves either a single electron transfer or a nucleophilic mechanism (Gaweska & Fitzpatrick, 2011; Zapata-Torres et al., 2015), either of which is more enzymically difficult when the amine electrons are hydrogen-bonded by the 4-hydroxy group (Figure 3a). Very recently, Lenz et al. (2022) have confirmed and extended the finding of the potential intramolecular hydrogen bond partially being responsible for slow MAO deamination as well as psilocin's enhanced ability to cross the blood–brain barrier. [...] This would explain why bufotenine is still an agonist at the 5-HT2A receptor but due to its poor physiochemical properties is not psychoactive in humans. }}</ref><ref name="McBride2000" /> However, psilocin appears to form a [[tricyclic compound|tricyclic]] [[Ring (chemistry)#Rings and ring systems|pseudo-ring system]] wherein its [[hydroxyl group]] and [[amine]] interact through [[hydrogen bond|hydrogen bonding]].<ref name="GumpperNichols2024" /><ref name="McBride2000" /><ref name="PlazasFaraone2023" /> This in turn results in psilocin being much less [[chemical polarity|polar]], more lipophilic, and more able to cross the blood–brain barrier and exert central actions than it would be otherwise.<ref name="GumpperNichols2024" /><ref name="McBride2000" /><ref name="PlazasFaraone2023" /> In contrast, bufotenin is not able to achieve this pseudo-ring system.<ref name="GumpperNichols2024" /><ref name="McBride2000" /><ref name="PlazasFaraone2023" /> Accordingly, bufotenin is less lipophilic than psilocin in terms of [[partition coefficient]].<ref name="GumpperNichols2024" /><ref name="McBride2000" /> In any case, bufotenin does still appear to show significant central permeability and, like psilocybin, can produce robust hallucinogenic effects in humans.<ref name="McBride2000" /><ref name="PlazasFaraone2023" /><ref name="ShenJiangWinter2010" /><ref name="Ott2001a" />

==Chemistry==
Bufotenin, also known as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a [[substituted tryptamine]] and a [[chemical derivative|derivative]] of [[dimethyltryptamine]] (DMT; ''N'',''N''-dimethyltryptamine) and [[serotonin]] (5-hydroxytryptamine; 5-HT).<ref name="TiHKAL" /> It is also closely related to [[psilocin]] (4-HO-DMT) and [[5-MeO-DMT]].<ref name="TiHKAL" />

===Properties===
The predicted [[partition coefficient|log P]] 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> 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> of 5-MeO-DMT is 1.5 to 2.38.<ref name="PubChem-5-MeO-DMT">{{cite web | title=N,N-Dimethyl-5-methoxytryptamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/1832 | access-date=22 January 2025}}</ref><ref name="ChemSpider-5-MeO-DMT">{{cite web | title=5-Methoxydimethyltryptamine | website=ChemSpider | date=10 June 2024 | url=https://www.chemspider.com/Chemical-Structure.1766.html | access-date=22 January 2025}}</ref><ref name="DrugBank-5-MeO-DMT">{{cite web | title=5-methoxy-N,N-dimethyltryptamine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=16 April 2018 | url=https://go.drugbank.com/drugs/DB14010 | access-date=22 January 2025}}</ref> and of psilocin is -0.14 to 2.1<!-- -0.14, 1.25, 1.32, and 2.1 -->.<ref name="PubChem-Psilocin">{{cite web | title=Psilocin | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/4980 | access-date=22 January 2025}}</ref><ref name="ChemSpider-Psilocin">{{cite web | title=C12H16N2O | website=ChemSpider | date=10 June 2024 | url=https://www.chemspider.com/Chemical-Structure.4807.html | access-date=22 January 2025}}</ref><ref name="DrugBank-Psilocin">{{cite web | title=Psilocybin: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=20 October 2016 | url=https://go.drugbank.com/drugs/DB11664 | access-date=22 January 2025}}</ref>

===Synthesis===
The [[chemical synthesis]] of bufotenin has been described.<ref name="TiHKAL" />

===Analogues and derivatives===
Some [[structural analog|analogue]]s and [[chemical derivative|derivative]]s of bufotenin (5-HO-DMT), aside from serotonin and DMT, include [[psilocin]] (4-HO-DMT) (a [[positional isomer]]), [[6-HO-DMT]] (another positional isomer), [[5-MeO-DMT]] (''O''-methylbufotenin), [[O-Acetylbufotenine|''O''-acetylbufotenine]] (5-AcO-DMT), [[O-Pivalylbufotenine|''O''-pivalylbufotenine]] (5-''t''-BuCO-DMT), [[bufotenidine]] (''N''-methylbufotenin), [[bufoviridine]] (bufotenin ''O''-sulfate), [[5-HO-DET]], [[5-HO-DPT]], [[5-HO-DiPT]], and [[α-methylserotonin]] (AMS; 5-HO-AMT), among others.<ref name="TiHKAL" />

==Natural occurrence==
===Toads===
Bufotenin is found in the skin and eggs of several species of toads belonging to the genus ''[[Bufo]]'', but is most concentrated in the [[Colorado River toad]] (formerly ''Bufo alvarius'', now ''Incilius alvarius''), the only toad species with enough bufotenin for a psychoactive effect. Extracts of [[toad toxin]], containing bufotenin and other [[Bioactive compound|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.<ref name=davis/> It is also found in the [[cane toad]] (''Rhinella marina'').<ref name="ChenLiYu2023a" />

The toad was "recurrently depicted in [[Mesoamerican]] 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 | 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 bufotenin, ''Bufo'' secretions also contain [[digoxin]]-like [[cardiac glycoside]]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 | vauthors = Ragonesi DL |year=1990 |title=The boy who was all hopped up |journal=Contemporary Pediatrics |volume=7 |pages=91–94}}</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 | vauthors = Lever C |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 [[street drug]], supposedly but in fact ''not'' an [[aphrodisiac]],<ref>Rodrigues, R.J. [http://www.ehealthstrategies.com/files/aphrodisia.pdf Aphrodisiacs through the Ages: The Discrepancy Between Lovers' Aspirations and Their Desires]. ehealthstrategies.com
</ref> ingested orally in the form of ''[[Bufotoxin#Extraction|ch'an su]]'',<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 [[West Indies]]) 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 name="Lyttle1993">{{cite journal | vauthors = Lyttle T | title = Misuse and legend in the "toad licking" phenomenon | journal = Int J Addict | volume = 28 | issue = 6 | pages = 521–538 | date = May 1993 | pmid = 8486435 | doi = 10.3109/10826089309039645 | url = }}</ref><ref>[https://www.npr.org/templates/story/story.php?storyId=6376594 The Dog Who Loved to Suck on Toads.] ''[[NPR]].'' Accessed on May 6, 2007.</ref><ref>[[Psychoactive toad#References|Psychoactive toad: Cultural references]]</ref> Albert Most, founder of the defunct [[Church of the Toad of Light]] and a proponent of spiritual use of ''[[Colorado River Toad|Bufo alvarius]]'' toxin, published a booklet in 1984 titled ''[[Bufo Alvarius: The Psychedelic Toad of the Sonoran Desert]]''<ref name="most">{{cite web | vauthors = 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 name="m076">{{cite web | title=Smoky Mountain News | website=smokymountainnews.com | date=16 July 2011 | url=http://www.smokymountainnews.com/issues/11_06/11_01_06/out_naturalist.html | archive-url=https://web.archive.org/web/20110928055000/http://www.smokymountainnews.com/issues/11_06/11_01_06/out_naturalist.html | archive-date=28 September 2011 | url-status=dead | access-date=28 March 2025}}</ref> which explained how to extract and smoke the secretions.

Bufotenin is also present in the skin secretion of three arboreal hylid frogs of the genus ''[[Osteocephalus]]'' (''[[Osteocephalus taurinus]]'', ''[[Osteocephalus oophagus]]'', and ''[[Osteocephalus langsdorfii]]'') from the [[Amazon Rainforest|Amazon]] and Atlantic [[rain forests]].<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===
[[File:Yopo_Seeds.jpg|thumb|right|Yopo seeds from the perennial ''[[Anadenanthera peregrina]]'' tree have a long history of entheogenic use and induce a short but distinct psychedelic experience.]]

Bufotenin is a constituent of the [[seeds]] of ''[[Anadenanthera colubrina]]'' and ''[[Anadenanthera peregrina]]'' trees. Anadenanthera seeds have been used as an ingredient in psychedelic [[hallucinogenic snuff|snuff]] preparations by indigenous cultures of the Caribbean, Central and South America since pre-Columbian times.<ref name="RepkeTorres2006">{{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" />

===Other sources===
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,<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 ''[[Mucuna pruriens]]''.<ref name="Chamakura1994" /> Bufotenin has also been identified in ''[[Amanita muscaria]],'' ''[[Amanita citrina]]'', ''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=[[CRC Press]] |isbn=978-0849301940 |pages=208}}</ref><ref>{{cite journal | vauthors = Buck RW | title = Toxicity of Amanita muscaria | journal = JAMA | volume = 185 | issue = 8 | pages = 663–664 | date = August 1963 | pmid = 14016551 | doi = 10.1001/jama.1963.03060080059020 }}</ref>

===Occurrence in 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 [[serotonin]] by [[indolethylamine N-methyltransferase|indolethylamine ''N''-methyltransferase]] (INMT) [[enzyme]]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 psychiatric conditions====
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 [[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.<ref name="pm20150873">{{cite journal | vauthors = 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 Endocrinology Letters | volume = 31 | issue = 1 | pages = 117–121 | year = 2010 | pmid = 20150873 }}</ref>

A 2025 systematic review of eight studies found that urinary bufotenine was detected more often and at higher concentrations in many patients with psychiatric diagnoses than in controls, but significant methodological heterogeneity and overlap between groups mean the evidence is currently insufficient to support bufotenine as a reliable biomarker for mental illness <ref>Clarke AJ. Elevated Endogenous Psychedelic Bufotenine in the Urine of Patients Diagnosed With a Mental Illness: A Systematic Review. Cureus. 2025 May 20;17(5):e84510. doi: https://doi.org/10.7759/cureus.84510. PMID: 40546466; PMCID: PMC12179411.</ref>

==History==
Bufotenine was first [[chemical isolation|isolated]] from [[secretion]]s of the [[toad]] ''[[Bufo vulgaris]]'' by [[French people|French]] [[scientist]]s [[Césaire Phisalix]] and Gabriel Bertrand in 1893.<ref name="Shulgin1981">{{cite journal | vauthors = Shulgin AT | title = Profiles of Psychedelic Drugs: Bufotenine | journal = J Psychoactive Drugs | volume = 13 | issue = 4 | pages = 389 | date = 1981 | pmid = 28557697 | doi = 10.1080/02791072.1981.10471899 | url = }}</ref><ref name="LyttleGoldsteinGartz1996">{{cite journal | vauthors = Lyttle T, Goldstein D, Gartz J | title = Bufo toads and bufotenine: fact and fiction surrounding an alleged psychedelic | journal = J Psychoactive Drugs | volume = 28 | issue = 3 | pages = 267–290 | date = 1996 | pmid = 8895112 | doi = 10.1080/02791072.1996.10472488 | url = }}</ref><ref name="BochnerGoyffon2007">Bochner, R., & Goyffon, M. (2007). L’œuvre scientifique de Césaire Phisalix (1852-1906), découvreur du sérum antivenimeux. Bull Soc Herp Fr, 123, 15-46. https://www.icict.fiocruz.br/sites/www.icict.fiocruz.br/files/L%20oeuvre%20scientifique%20de%20Cesaire%20Phisalix%20(1852--1906)%20decouvreur%20du%20serum%20antivenimeux.pdf</ref><ref name="PhisalixBertrand1893">Phisalix C, Bertrand G (1893) Toxicité comparée du sang et du venin de crapaud commun, considérée au point de vue de la sécrétion interne des glandes cutanées de cet animal. C R Soc Biol 45:477–479. https://scholar.google.com/scholar?cluster=14905926340091797397</ref> It was also subsequently isolated from many other [[natural product|natural source]]s, including [[plant]]s, [[fungi]], and other toads over time.<ref name="Shulgin1981" /><ref name="Chamakura1994" /> The compound was first isolated to [[chemical purity|purity]] by [[Austrian people|Austrian]] [[chemist]] Hans Handovsky in 1920.<ref name="LyttleGoldsteinGartz1996" /><ref name="ChiltonBigwoodJensen1979">{{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 [[chemical structure]] of bufotenine was confirmed by [[German people|German]] chemist [[Heinrich Wieland]] and colleagues in 1934.<ref name="WielandKonzMittasch1934">{{cite journal | vauthors = Wieland H, Konz W, Mittasch H | title=Die Konstitution von Bufotenin und Bufotenidin. Über Kröten-Giftstoffe. VII | trans-title=The Constitution of Bufotenin and Bufotenidin. On Toad Toxins. VII | journal=Justus Liebigs Annalen der Chemie | volume=513 | issue=1 | date=1934 | issn=0075-4617 | doi=10.1002/jlac.19345130102 | pages=1–25}}</ref> The first reported [[chemical synthesis|synthesis]] of bufotenine was by [[Japanese people|Japanese]] researchers [[:ja:星野敏雄|Toshio Hoshino]] and Kenya Shimodaira in 1935.<ref name="HoshinoShimodaira1935">{{cite journal | vauthors = Hoshino T, Shimodaira K | 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}}</ref>

Bufotenin was established as a major component of [[hallucinogenic snuff]]s made from ''[[Anadenanthera peregrina]]'' such as [[cohoba]] and [[yopo]] in 1954.<ref name="Shulgin1981" /><ref name="Chamakura1994" /><ref name="Stromberg1954">{{cite journal |  vauthors = Stromberg VL | title=The Isolation of Bufotenine from Piptadenia peregrina | journal=Journal of the American Chemical Society | volume=76 | issue=6 | date=1954 | issn=0002-7863 | doi=10.1021/ja01635a082 | pages=1707| bibcode=1954JAChS..76.1707S }}</ref><ref name="FishHorning1956">{{cite journal | vauthors = Fish MS, Horning EC | title = Studies on hallucinogenic snuffs | journal = J Nerv Ment Dis | volume = 124 | issue = 1 | pages = 33–37 | date = July 1956 | pmid = 13416916 | doi = 10.1097/00005053-195607000-00004 | url = https://www.samorini.it/doc1/alt_aut/ek/fisch.htm| url-access = subscription }}</ref> It was also isolated from ''[[Anadenanthera colubrina]]'' in 1955.<ref name="Chamakura1994" /><ref name="FishJohnsonHorning1955">{{cite journal | title=Piptadenia Alkaloids. Indole Bases of P. peregrina (L.) Benth. and Related Species | journal=Journal of the American Chemical Society | volume=77 | issue=22 | date=1955 | issn=0002-7863 | doi=10.1021/ja01627a034 | pages=5892–5895 | bibcode=1955JAChS..77.5892F | vauthors = Fish MS, Johnson NM, Horning EC }}</ref><ref name="FishHorning1956" /> [[Clinical study|Clinical studies]] assessed the effects of bufotenin and were published starting in 1956.<ref name="LyttleGoldsteinGartz1996" /><ref name="McBride2000" /><ref name="ShenJiangWinter2010" /><ref name="FabingHawkins1956" /><ref name="TurnerMerlis1959" /> However, the findings of these studies were conflicting, and bufotenin developed a long-standing reputation of being non-[[hallucinogen]]ic as well as [[toxicity|toxic]].<ref name="LyttleGoldsteinGartz1996" /><ref name="McBride2000" /><ref name="ShenJiangWinter2010" /> In any case, bufotenin nonetheless became a [[Controlled Substances Act#Schedule I|Schedule I]] [[controlled substance]] in the [[United States]] in 1967.<ref name="Lyttle1993" /><ref name="LyttleGoldsteinGartz1996" /><ref name="ChiltonBigwoodJensen1979"/>

[[American people|American]] [[ethnobotanist]] [[Jonathan Ott]] and colleagues subsequently showed in 2001 that bufotenin is in fact a psychedelic and does not necessarily produce major [[adverse effect]]s, although marked [[nausea]] and [[vomiting]] are prominent.<ref name="ShenJiangWinter2010" /><ref name="Ott2001b" /><ref name="Ott2001a" /> Bufotenin was first encountered as a novel [[recreational drug]] in 1992.<ref name="Chamakura1994" /> [[Journalist]] [[Hamilton Morris]] corroborated Ott and colleagues' findings on the hallucinogenicity of bufotenin in the early 2020s.<ref name="Morris2022" /><ref name="MorrisOtt2023" />

==Society and culture==
===Names===
Bufotenin, or 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>

===Recreational use===
Bufotenin has been encountered as a [[recreational drug]] in forensic samples, for instance in [[New York City]].<ref name="Chamakura1994">{{cite journal | vauthors = Chamakura RP | 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 = 1–18 | date = June 1994 | pmid = 26270149 | doi = | url = https://bibliography.maps.org/resources/download/12014| archive-url = https://web.archive.org/web/20220417052430/https://bibliography.maps.org/resources/download/12014 | archive-date = 17 April 2022 }}</ref>

===Legal status===
====Australia====
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 [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard]] (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 Poisons Act 1964 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>[http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:26063P/$FILE/Poisons%20Act%201964%20-%20%5B09-f0-04%5D.pdf?OpenElement Poisons Act 1964] {{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 Misuse of Drugs Act 1981 {{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>[http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:28280P/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement Misuse of Drugs Act 1981 (2015)] {{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>

====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>

====United Kingdom====
In the United Kingdom, bufotenin is a Class A drug under the 1971 [[Misuse of Drugs Act 1971|Misuse of Drugs Act]].

====United States====
Bufotenin (DEA Drug Code 7403) is regulated as a [[Controlled Substances Act#Schedule I controlled substances|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.<ref name="PART 1308 — SCHEDULES OF CONTROLLED SUBSTANCES - 1308.11 Schedule I">[http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm §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>

==Research==
Bufotenin is being investigated as a potential [[pharmaceutical drug]] by the [[Usona Institute]].<ref name="Synapse">{{cite web | title=Delving into the Latest Updates on Bufotenine with Synapse | website=Synapse | date=8 May 2025 | url=https://synapse.patsnap.com/drug/c4f01e5a6c084a7986c80624c182924b | access-date=10 May 2025}}</ref> As of May 2025, it is in the discovery or [[preclinical research]] stage of development.<ref name="Synapse" />

Bufotenin has shown [[antiviral]] activity against the [[rabies virus]] and has been found to increase survival rates against [[rabies]] in rodents.<ref name="CoelhodaSilvaBeraldo-Neto2021">{{cite journal | vauthors = Coelho GR, da Silva DL, Beraldo-Neto E, Vigerelli H, de Oliveira LA, Sciani JM, Pimenta DC | title = Neglected Venomous Animals and Toxins: Underrated Biotechnological Tools in Drug Development | journal = Toxins (Basel) | volume = 13 | issue = 12 | date = November 2021 | page = 851 | pmid = 34941689 | pmc = 8708286 | doi = 10.3390/toxins13120851 | doi-access = free | url = }}</ref><ref name="VigerelliScianiPereira2020">{{cite journal | vauthors = Vigerelli H, Sciani JM, Pereira PM, Lavezo AA, Silva AC, Collaço RC, Rocha T, Bueno TC, Pimenta DC | title = Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment | journal = J Venom Anim Toxins Incl Trop Dis | volume = 26 | issue = | article-number = e20190050 | date = 2020 | pmid = 32071597 | pmc = 6996410 | doi = 10.1590/1678-9199-JVATITD-2019-0050 | url = }}</ref>

==See also==
* [[Substituted tryptamine]]
* [[List of entheogens]]

==References==
{{Reflist}}

==External links==
* [https://isomerdesign.com/pihkal/explore/5019 Bufotenin - Isomer Design]
* [https://psychonautwiki.org/wiki/Bufotenin Bufotenin - PsychonautWiki]
* [https://www.erowid.org/chemicals/bufotenin/bufotenin.shtml Bufotenin - Erowid]
* [https://www.bluelight.org/xf/threads/61866 The Big & Dandy Bufotenine (5-HO-DMT) Thread - Bluelight]
* [http://www.erowid.org/library/books_online/tihkal/tihkal19.shtml Bufotenin - TiHKAL - Erowid]
* [http://tihkal.info/read.php?domain=tk&id=19 Bufotenin - TiHKAL - Isomer Design]
* [https://bitnest.netfirms.com/external/SST/103-111 Bufotenin - Trout's Notes]
* [https://tripsitter.com/bufo-alvarius/ Psychoactive Toad Venom (Bufo Alvarius) - Tripsitter]
* [https://tripsitter.com/dmt/yopo/ Yopo (Anadenanthera peregrina): Psychedelic Snuff From the Amazon - Tripsitter]

{{Neurotransmitters}}
{{Psychedelics}}
{{Serotonin receptor modulators}}
{{Monoamine releasing agents}}
{{Tryptamines}}

[[Category:5-HT1A agonists]]
[[Category:5-HT2A agonists]]
[[Category:5-HT2C agonists]]
[[Category:5-HT3 agonists]]
[[Category:5-HT4 agonists]]
[[Category:Amphibian toxins]]
[[Category:N,N-Dialkyltryptamines]]
[[Category:Emetics]]
[[Category:Entheogens]]
[[Category:Hamilton Morris]]
[[Category:5-Hydroxytryptamines]]
[[Category:Peripherally selective drugs]]
[[Category:Plant toxins]]
[[Category:Psychedelic tryptamines]]
[[Category:Serotonin receptor agonists]]
[[Category:Serotonin releasing agents]]
[[Category:Substances discovered in the 1930s]]
[[Category:Tryptamine alkaloids]]