Bufotenin

Bufotenin
Clinical data
Other namesBufotenine; 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
Routes of
administration		Oral, intranasal/insufflation, inhalation, sublingual, rectal, intravenous[1]
Drug classSerotonergic psychedelic; Hallucinogen; Serotonin receptor agonist; Serotonin 5-HT2A receptor agonist
ATC code
  • None
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • CA: Unscheduled
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • US: Schedule I
  • Illegal in Sweden
Pharmacokinetic data
BioavailabilityWeakly active (with or without MAOITooltip monoamine oxidase inhibitor)[2][1]
MetabolismDeamination via MAO-ATooltip monoamine oxidase A and conjugation (glucuronidation, sulfation)[3][6]
Metabolites• 5-HIAATooltip 5-Hydroxyindoleacetic acid[3]
• Glucuronide and sulfate conjugates[3]
Onset of actionPOTooltip Oral administration: 20 min[2][1]
INTooltip Intranasal administration: 5–15 min[2][1]
SLTooltip Sublingual administration: 5–15 min[2][1]
RECTooltip Rectal administration: ~15 min[2][1]
INHTooltip Inhalational administration: ≤1–2 min[2][1]
IVTooltip Intravenous injection: <1 min[4]
Duration of actionPOTooltip Oral administration: ~2 hours[1]
INTooltip Intranasal administration: 30–90 min[2][1][5]
SLTooltip Sublingual administration: 30–90 min[2][1]
RECTooltip Rectal administration: ~1 hour[2][1]
INHTooltip Inhalational administration: 60–90 min[2][1]
IVTooltip Intravenous injection: ~5–120 min[2]
Identifiers
IUPAC name
  • 3-[2-(Dimethylamino)ethyl]-1H-indol-5-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.971
Chemical and physical data
FormulaC12H16N2O
Molar mass204.273 g·mol−1
3D model (JSmol)
Melting point146 to 147 °C (295 to 297 °F)
Boiling point320 °C (608 °F)
SMILES
  • CN(C)CCc1c[nH]c2ccc(O)cc12
InChI
  • InChI=1S/C12H16N2O/c1-14(2)6-5-9-8-13-12-4-3-10(15)7-11(9)12/h3-4,7-8,13,15H,5-6H2,1-2H3 Y
  • Key:VTTONGPRPXSUTJ-UHFFFAOYSA-N Y
  (verify)

Bufotenin, also known as dimethylserotonin or as 5-hydroxy-N,N-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a 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 mushrooms, plants, and toads. It is also found naturally in the human body in small amounts.[7][8][9] Bufotenin, for instance derived from the trees Anadenanthera colubrina and Anadenanthera peregrina, has a long history of entheogenic use as a snuff in South America.[1][5][10][11]

The name bufotenin originates from the toad genus Bufo, which includes several species of psychoactive toads, most notably Incilius alvarius (formerly Bufo alvarius), that secrete bufotoxins from their parotoid glands.[12] 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 potent and non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT3 receptors, among others.[13][6][8][14] It also acts as a potent and specific serotonin releasing agent.[14] The compound is more hydrophilic than other related tryptamines and consequently is more peripherally selective.[13][15] In relation to this, bufotenin has been associated with prominent peripheral serotonergic side effects, such as cardiovascular changes.[13][8][16] The cardiovascular effects of bufotenin can be powerful and potentially dangerous.[17]

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 toxic effects.[15][2][13][3] Alexander Shulgin was also uncertain whether bufotenin was an active psychedelic.[16][18][5] 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.[3][5][2][1] Hamilton Morris has further supported these findings with his own self-experimentation, although bufotenin was reported to be strongly nauseating for himself and many others.[10][5] According to Morris, the psychedelic effects of bufotenin are like a cross between those of DMT and 5-MeO-DMT.[10][5] Morris has stated that bufotenin may in fact be the psychedelic with the longest history of human entheogenic use.[10][5] Bufotenin has also been encountered as a recreational drug in forensic samples, for instance in New York City.[19]

  1. ^ a b c d e f g h i j k l m n Cite error: The named reference Ott2001a was invoked but never defined (see the help page).
  2. ^ a b c d e f g h i j k l m Ott J (2001). "Shamanic-Snuff Psychonautica: Pharmañopo: Bufotenine—Psychonautics". Shamanic Snuffs or Entheogenic Errhines. Entheobotanica. pp. 99–116 (105–112, 114–115). ISBN 978-1-888755-02-2. OCLC 56061312. Retrieved 24 January 2025.
  3. ^ a b c d e Cite error: The named reference ShenJiangWinter2010 was invoked but never defined (see the help page).
  4. ^ Cite error: The named reference FabingHawkins1956 was invoked but never defined (see the help page).
  5. ^ a b c d e f g Hamilton Morris (1 September 2021). "PODCAST 28: A talk with Jonathan Ott". The Hamilton Morris Podcast (Podcast). Patreon. Event occurs at 49:20–50:36. Retrieved 20 January 2025. [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.
  6. ^ a b Cite error: The named reference PlazasFaraone2023 was invoked but never defined (see the help page).
  7. ^ Barker SA, McIlhenny EH, Strassman R (2012). "A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010". Drug Test Anal. 4 (7–8): 617–635. doi:10.1002/dta.422. PMID 22371425.
  8. ^ a b c Cite error: The named reference NeumannDheinKirchhefer2024 was invoked but never defined (see the help page).
  9. ^ Kärkkäinen J, Forsström T, Tornaeus J, Wähälä K, Kiuru P, Honkanen A, et al. (2005). "Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues". Scand J Clin Lab Invest. 65 (3): 189–199. doi:10.1080/00365510510013604. PMID 16095048.
  10. ^ a b c d Hamilton Morris (1 December 2022). "A New One-Hour Talk On 5-MeO-DMT". The Hamilton Morris Podcast. Patreon. Event occurs at 6:27–8:40, 10:15–11:13. Retrieved 21 January 2025. [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.
  11. ^ Tittarelli R, Mannocchi G, Pantano F, Romolo FS (January 2015). "Recreational use, analysis and toxicity of tryptamines". Curr Neuropharmacol. 13 (1): 26–46. doi:10.2174/1570159X13666141210222409. PMC 4462041. PMID 26074742.
  12. ^ Bufo Alvarius. AmphibiaWeb. Accessed on May 6, 2007.
  13. ^ a b c d Cite error: The named reference McBride2000 was invoked but never defined (see the help page).
  14. ^ a b Cite error: The named reference BloughLandavazoDecker2014 was invoked but never defined (see the help page).
  15. ^ a b Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". Br J Pharmacol. doi:10.1111/bph.17361. PMID 39354889. 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.
  16. ^ a b Shulgin AT, Shulgin A (1997). TiHKAL: The Continuation (1st ed.). Berkeley, CA: Transform Press. ISBN 9780963009692. OCLC 38503252. 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.
  17. ^ Holmstedt B, Daly JW, Del Pozo EC, Horning EC, Isbel H, Szara S (1967). "Discussion on the Psychoactive Action of Various Tryptamine Derivatives". Ethnopharmacologic Search for Psychoactive Drugs. Raven Press. pp. 374–382 (377). ISBN 978-0-89004-047-8. [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.
  18. ^ Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Retrieved 1 February 2025. 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.
  19. ^ Cite error: The named reference Chamakura1994 was invoked but never defined (see the help page).
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