6-Hydroxy-DMT

Pharmaceutical compound From Wikipedia, the free encyclopedia

6-Hydroxy-DMT, or 6-HO-DMT, also known as 6-hydroxy-N,N-dimethyltryptamine, is a serotonin receptor modulator of the tryptamine family related to the psychedelic drug dimethyltryptamine (DMT).^[1]^[2]^[3]^[4]^[5] It is a major metabolite of DMT in rodents but a minor metabolite of DMT in humans.^[4]^[6]^[7] The drug is the 6-hydroxy analogue of DMT and is a positional isomer of bufotenin (5-HO-DMT) and psilocin (4-HO-DMT).^[2]^[3]^[8]

Other names6-HDMT; 6-HO-DMT; 6-OH-DMT; 6-Hydroxy-N,N-dimethyltryptamine

Drug classSerotonin receptor modulator

ATC code

None

CAS Number

1476-33-1

Quick facts Clinical data, Other names ...

6-Hydroxy-DMT
Clinical data


Other names	6-HDMT; 6-HO-DMT; 6-OH-DMT; 6-Hydroxy-N,N-dimethyltryptamine
Drug class	Serotonin receptor modulator
ATC code	None
Identifiers
IUPAC name 3-[2-(dimethylamino)ethyl]-1H-indol-6-ol
CAS Number	1476-33-1
PubChem CID	15124
ChemSpider	14396
ChEMBL	ChEMBL382750
CompTox Dashboard (EPA)	DTXSID70163752
Chemical and physical data
Formula	C₁₂H₁₆N₂O
Molar mass	204.273 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CN(C)CCC1=CNC2=C1C=CC(=C2)O
InChI InChI=1S/C12H16N2O/c1-14(2)6-5-9-8-13-12-7-10(15)3-4-11(9)12/h3-4,7-8,13,15H,5-6H2,1-2H3 Key:WUQMRWPLIMXBDX-UHFFFAOYSA-N

Use and effects

6-Hydroxy-DMT was completely inactive in terms of psychoactive and autonomic effects at doses of 0.75 to 1 mg/kg (~53–70 mg for a 70-kb person) by intramuscular injection in humans.^[1]^[2]^[5] The drug was said to be indistinguishable from placebo.^[5] Conversely, DMT produced strong hallucinogenic effects at the same doses.^[5]

Pharmacology

Although it was inactive as a psychedelic in humans, 6-hydroxy-DMT has been found to produce pharmacological effects in animals, albeit with diminished potency compared to dimethyltryptamine (DMT).^[4]^[2]^[8]^[9] As examples, in terms of behavioral effects, 6-hydroxy-DMT was ≥3-fold less potent in rats, >10-fold less potent in cats, and 3-fold less potent in monkeys.^[4] It was suggested by Richard Glennon and colleagues that the reduced activity of 6-hydroxy-DMT may be due to its greater hydrophilicity and reduced ability to penetrate the blood–brain barrier analogously to the case of bufotenin.^[8]

Subsequent research assessed 6-hydroxy-DMT at the serotonin receptors in vitro.^[7] It was found to have detectable but very low affinity for the serotonin 5-HT₂ receptors (K_i ≥ 6,300–19,000 nM).^[7]

Chemistry

Properties

The predicted log P of 6-HO-DMT is 2.4.^[10] For comparison, the predicted log P of psilocin (4-HO-DMT) is 2.1^[11] and of bufotenin (5-HO-DMT) is 1.2.^[12]

Analogues

Analogues of 6-hydroxy-DMT include 6-hydroxytryptamine (6-HT or 6-HO-T), dimethyltryptamine (DMT), 6-HO-DMT, 6-MeO-DMT, 5,6-MDO-DMT, 6-methyl-DMT, and 6-fluoro-DMT, among others.

History

6-Hydroxy-DMT was first described in the scientific literature by at least 1962.^[13]

Society and culture

Legal status

United States

6-Hydroxy-DMT is a Schedule I controlled substance in the United States as a positional isomer of psilocin.^[14]^[15]

References

[1]
Shulgin A, Shulgin A (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. "6-HO-DMT is a minor metabolite of DMT in man, and it was studied for the same reasons. Could this compound play a role in explaining the activity of the parent dialkylamine? It was explored in a series of subjects who had responded spectacularly to DMT. The five volunteers in this study were former opium addicts who were serving sentences for violation of United States narcotics laws. They were administered 6-HO-DMT at either 0.75 mg/kg (one subject) or 1.0 mg/kg (four subjects) and reported no differences from the inactive placebo control. The objective measures (blood pressure, respiration and heart rate, pupillary dilation) confirmed this absence of activity at this level. The active control drug was DMT itself, and it showed the expected responses in all regards." [...] "It is pretty generally accepted that 6-HO-DMT is inactive. I am not too surprised. There are so few things with open and exposed hydroxyl groups that succeed in making it through the lipid barriers that protect to the brain."
[2]
Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. In fact, animal studies with 6-hydroxy-N,N-dimethyltryptamine suggested that the compound was indeed more potent that its parent (Szara and Hearst, 1962). [...] 6-Hydroxy-5-methoxy-N,Ndiniethyltryptamine [(XXXV), R1 = OCH3 , R 2 = R3 = CH3] appeared to be less potent than 5-methoxy-N,N-dimethyltryptamine (Taborsky et al., 1966) and 6-hydroxy-5-methoxytryptamine [(XXXV), R1 = OCH3 , R2 = R3 = H] was less potent than 5-methoxytryptamine (Taborsky et al., 1965). In animal studies (Uyeno, 1969) as well as human studies (Rosenberg et al., 1963), 6-hydroxy-N,N-dimethyltryptamine [(XXXV), R 1 = H, R2 = R3 = CH3] was inactive at 1 mgfkg, whereas N,N-dimethyltryptamine is clinically effective at this dosage. [...] The present evidence indicates that chemical substitution on the 6 position of the tryptamine system destroys the psychotomimetic potential of the compound.
[3]
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.
[4]
Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M.
[5]
Rosenberg DE, Isbell H, Miner EJ (February 1963). "Comparison of a placebo, N-dimethyltryptamine, and 6-hydroxy-N-dimethyltryptamine in man". Psychopharmacologia. 4: 39–42. doi:10.1007/BF00429362. PMID 14050410.
[6]
Barker SA, Monti JA, Christian ST (1981). "N,N-Dimethyltryptamine: An Endogenous Hallucinogen". International Review of Neurobiology Volume 22. Vol. 22. pp. 83–110. doi:10.1016/s0074-7742(08)60291-3. ISBN 978-0-12-366822-6. PMID 6792104.
[7]
Sard H, Kumaran G, Morency C, Roth BL, Toth BA, He P, et al. (October 2005). "SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist". Bioorganic & Medicinal Chemistry Letters. 15 (20): 4555–4559. doi:10.1016/j.bmcl.2005.06.104. PMID 16061378.
[8]
Glennon RA, Rosecrans JA (1982). "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neuroscience and Biobehavioral Reviews. 6 (4): 489–497. doi:10.1016/0149-7634(82)90030-6. PMID 6757811. 6-Hydroxy DMT (3f) displays only weak behavioral activity in animals [10, 73, 74] and is not hallucinogenic in man [55]. It may be argued that the lipid solubility of 6-hydroxy DMT, like that of bufotenine, will not allow it to penetrate into the brain; this might account for its inactivity. [...] It might be speculated that 6-hydroxy DMT, like bufotenine, would display more activity if it were made more lipid soluble by, for example, acylation of the hydroxyl group. Although this is an intriguing possibility, its likelihood is not supported by the low order of activity of its O-methyl ether 6-OMe DMT (3g) [20,27].
[9]
Uyeno ET (1971). "Relative potency of amphetamine derivatives and N,N-dimethyltryptamines". Psychopharmacologia. 19 (4): 381–387. doi:10.1007/BF00404382. PMID 5565249.
[10]
"3-(2-(Dimethylamino)ethyl)-1H-indol-6-ol". PubChem. Retrieved 5 November 2025.
[11]
"Psilocin". PubChem. Retrieved 5 November 2025.
[12]
"Bufotenine". PubChem. Retrieved 5 November 2025.
[13]
Hearst E, Putney F, Szara S (1962). "Metabolism and behavioural action of psychotropic tryptamine homologues". International Journal of Neuropharmacology. 1 (1–3): 111–117. doi:10.1016/0028-3908(62)90015-1.
[14]
Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) (PDF), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026
[15]
Drug Enforcement Administration (3 December 2007). "Definition of "Positional Isomer" as It Pertains to the Control of Schedule I Controlled Substances". Federal Register.