Chemistry:O-Acetylbufotenine

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Short description: Psychedelic tryptamine


O-Acetylbufotenine
Clinical data
Other namesO-Acetylbufotenin; Bufotenine acetate; Bufotenin acetate; Bufotenine O-acetate; Bufotenin O-acetate; 5-Acetoxy-N,N-dimethyltryptamine; 5-Acetoxy-DMT; 5-AcO-DMT; 5-Acetoxy-N,N-DMT; O-Acetyl-N,N-dimethylserotonin
Drug classSerotonin receptor agonist; Serotonergic psychedelic
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC14H18N2O2
Molar mass246.310 g·mol−1
3D model (JSmol)

O-Acetylbufotenine, or bufotenine O-acetate, also known as 5-acetoxy-N,N-dimethyltryptamine (5-AcO-DMT) or O-acetyl-N,N-dimethylserotonin, is a synthetic tryptamine derivative and putative serotonergic psychedelic.[1][2][3][4] It is the O-acetylated analogue of the naturally occurring peripherally selective serotonergic tryptamine bufotenine (5-hydroxy-N,N-dimethyltrypamine or N,N-dimethylserotonin) and is thought to act as a centrally penetrant prodrug of bufotenine.[1][2][3][4]

Use and effects

The effects of O-acetylbufotenine in humans have not been assessed or reported.[2][1] Alexander Shulgin speculated about O-acetylbufotenine in his 1997 book TiHKAL (Tryptamines I Have Known and Loved), but did not personally synthesize or test it.[4]

Interactions

Pharmacology

Bufotenin has low lipophilicity, limitedly crosses the blood–brain barrier in animals, does not produce psychedelic-like effects in animals except at very high doses or administered directly into the brain, and produces inconsistent and weak psychedelic effects accompanied by pronounced peripheral side effects in humans.[1][2][5][6][4] O-Acetylbufotenine, which is much more lipophilic than bufotenine due to its acetyl group, was developed in an attempt to overcome bufotenine's limitations and allow for the drug to efficiently cross the blood–brain barrier.[2][4] In contrast to peripherally administered bufotenine, O-acetylbufotenine readily enters the brain in animals and produces robust psychedelic-like effects.[2][3][1] In addition, O-acetylbufotenine was more potent than N,N-dimethyltryptamine (DMT) or 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-methylbufotenine) in animals.[2][3]

O-Acetylbufotenine is thought to be a prodrug of bufotenine, which is a non-selective agonist of many of the serotonin receptors, including of the serotonin 5-HT2A receptor (the activation of which is associated with psychedelic effects).[5][7][6] However, O-acetylbufotenine has also unexpectedly been found to act directly as an agonist of certain serotonin receptors, including of the serotonin 5-HT1A and 5-HT1D receptors.[8][9]

The O-acetyl substitution of O-acetylbufotenine is expected to be cleaved quite rapidly in vivo, which may hinder the ability of O-acetylbufotenine to cross the blood–brain barrier and deliver bufotenine into the central nervous system.[2] This might be overcome with other O-acyl bufotenin derivatives.[2][8]

Chemistry

Analogues

Analogues of O-acetylbufotenin (5-AcO-DMT) include bufotenin (5-HO-DMT), 4-AcO-DMT (psilacetin), 5-MeO-DMT, 5-EtO-DMT, 5-HO-DET, 5-HO-DPT, 5-HO-DiPT, and α-methylserotonin (5-HO-AMT), among others. In addition, other O-acyl derivatives of bufotenin besides O-acetylbufotenine have been developed and studied.[2][8] One such analogue, O-pivalylbufotenine, has been assessed and has likewise been shown to produce psychedelic-like effects animals.[2][3][8]

History

O-Acetylbufotenine was first described in the scientific literature by 1968.[10][11] It was sold online as an analytical standard by 2023.[12]

Society and culture

Canada

O-Acetylbufotenine is not an explicitly nor implicitly controlled substance in Canada as of 2025.[13]

United States

O-Acetylbufotenine is not an explicitly controlled substance in the United States.[14] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. "The weak activity at 5 mg./kg. (s.c.) of 5-hydroxy-N,N-diethyltryptamine in the open field test with rats may well be due to a similar lack of lipid solubility [as bufotenin] and consequent poor entry into the brain (Hunt and Brimblecombe, 1967). 5-Acetoxy-N,N-dimethyltryptamine may be worthy of a clinical trial as a lipid-soluble derivative of bufotenin, since the compound is very effective in disrupting conditioned avoidance responses in rodents (Gessner and others, 1968; Gessner, 1970)." 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neuroscience & Biobehavioral Reviews 6 (4): 489–497. 1982. doi:10.1016/0149-7634(82)90030-6. PMID 6757811. "In an effort to overcome this problem of poor lipid solubility, Gessner et al. [20] prepared 5-acetoxy DMT (i.e., O-acetyl bufotenine), which was found to possess a greater lipid solubility than bufotenine, and, which should be hydrolyzed to bufotenine once it has entered the brain. Animal studies reveal that 5-acetoxy DMT is behaviorally active, and more active than either DMT or 5-OMe DMT [17]. No human studies have been performed with 5-acetoxy bufotenine.". 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. 1984. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237. https://bitnest.netfirms.com/external/Books/HallucinogensNBCP95. "Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65, 74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine; 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels Of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74)." 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Shulgin & Shulgin. TiHKAL #19. 5-HO-DMT
  5. ↑ 5.0 5.1 "Bufotenine: toward an understanding of possible psychoactive mechanisms". Journal of Psychoactive Drugs 32 (3): 321–331. 2000. doi:10.1080/02791072.2000.10400456. PMID 11061684. 
  6. ↑ 6.0 6.1 "Effects of hallucinogenic drugs on the human heart". Frontiers in Pharmacology 15. 2024. doi:10.3389/fphar.2024.1334218. PMID 38370480. 
  7. ↑ "Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents". Biomedicines 11 (2): 461. February 2023. doi:10.3390/biomedicines11020461. PMID 36830997. 
  8. ↑ 8.0 8.1 8.2 8.3 "Bufotenine esters". Journal of Medicinal Chemistry 22 (11): 1414–1416. November 1979. doi:10.1021/jm00197a025. PMID 533890. 
  9. ↑ "Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors". Journal of Medicinal Chemistry 39 (1): 314–22. January 1996. doi:10.1021/jm950498t. PMID 8568822. 
  10. ↑ "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sciences 7 (5): 267–77. March 1968. doi:10.1016/0024-3205(68)90200-2. PMID 5641719. 
  11. ↑ "Brain Bufotenine from Administered Acetylbufotenine: Comparison of Its Tremorgenic Activity with That of N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine.". Pharmacologist 17 (2): 259. January 1975. 
  12. ↑ "5-AcO-DMT (5-acetoxy DMT)" (in ru). 5 January 1996. https://aipsin.com/newsubstance/1107/. 
  13. ↑ "Controlled Drugs and Substances Act". 5 December 2025. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  14. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 



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