{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = 6-Hydroxy-DMT.svg | image_class = skin-invert-image | width = 225px | image2 = 6-Hydroxy-DMT 3D.png | image_class2 = bg-transparent | width2 = 225px
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = Serotonin receptor modulator | ATC_prefix = None | ATC_suffix =
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<!-- Identifiers --> | CAS_number = 1476-33-1 | CAS_supplemental = | PubChem = 15124 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = 14396 | UNII = | KEGG = | ChEBI = | ChEMBL = 382750 | NIAID_ChemDB = | PDB_ligand = | synonyms = 6-HDMT; 6-HO-DMT; 6-OH-DMT; 6-Hydroxy-''N'',''N''-dimethyltryptamine
<!-- Chemical data --> | IUPAC_name = 3-[2-(dimethylamino)ethyl]-1''H''-indol-6-ol | C=12 | H=16 | N=2 | O=1 | SMILES = CN(C)CCC1=CNC2=C1C=CC(=C2)O | StdInChI = 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 | StdInChIKey = WUQMRWPLIMXBDX-UHFFFAOYSA-N }}
'''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).<ref name="TiHKAL">{{CiteTiHKAL }} "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."</ref><ref name="Shulgin_1976" /><ref name="Shulgin_2003">{{cite book | vauthors = Shulgin AT | veditors = Laing RR | chapter = Basic Pharmacology and Effects | title = Hallucinogens: A Forensic Drug Handbook | pages = 67–137 | year = 2003 | publisher = Elsevier Science | series = Forensic Drug Handbook Series | 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 }}</ref><ref name="Brimblecombe_1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | title = Hallucinogenic Agents | location = Bristol | pages = 98–144 | date = 1975 | publisher = Wright-Scientechnica | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 }}</ref><ref name="Rosenberg_1963">{{cite journal | vauthors = Rosenberg DE, Isbell H, Miner EJ | title = Comparison of a placebo, N-dimethyltryptamine, and 6-hydroxy-N-dimethyltryptamine in man | journal = Psychopharmacologia | volume = 4 | pages = 39–42 | date = February 1963 | pmid = 14050410 | doi = 10.1007/BF00429362 }}</ref> It is a major metabolite of DMT in rodents but a minor metabolite of DMT in humans.<ref name="Brimblecombe_1975" /><ref name="Barker_1981">{{cite book | vauthors = Barker SA, Monti JA, Christian ST | chapter = N,N-Dimethyltryptamine: An Endogenous Hallucinogen | title = International Review of Neurobiology Volume 22 | volume = 22 | pages = 83–110 | date = 1981 | pmid = 6792104 | doi = 10.1016/s0074-7742(08)60291-3 | isbn = 978-0-12-366822-6 }}</ref><ref name="Sard_2005" /> The drug is the 6-hydroxy analogue of DMT and is a positional isomer of bufotenin (5-HO-DMT) and psilocin (4-HO-DMT).<ref name="Shulgin_1976" /><ref name="Shulgin_2003" /><ref name="Glennon_1982" />
==Use and effects== 6-Hydroxy-DMT was completely inactive in terms of psychoactive and autonomic effects at doses of 0.75 to 1{{nbsp}}mg/kg (~53–70{{nbsp}}mg for a 70-kb person) by intramuscular injection in humans.<ref name="TiHKAL" /><ref name="Shulgin_1976">{{cite book | vauthors = Shulgin AT | veditors = Gordon M | chapter = Psychotomimetic Agents | title = Psychopharmacological Agents: Use, Misuse and Abuse | volume = 4 | pages = 59–146 | date = 1976 | doi = 10.1016/b978-0-12-290559-9.50011-9 | series = Medicinal Chemistry: A Series of Monographs | isbn = 978-0-12-290559-9 | publisher = Academic Press | chapter-url = https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9 | quote = 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. }}</ref><ref name="Rosenberg_1963" /> The drug was said to be indistinguishable from placebo.<ref name="Rosenberg_1963" /> Conversely, DMT produced strong hallucinogenic effects at the same doses.<ref name="Rosenberg_1963" />
==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).<ref name="Brimblecombe_1975" /><ref name="Shulgin_1976" /><ref name="Glennon_1982">{{cite journal | vauthors = Glennon RA, Rosecrans JA | title = Indolealkylamine and phenalkylamine hallucinogens: a brief overview | journal = Neuroscience and Biobehavioral Reviews | volume = 6 | issue = 4 | pages = 489–497 | date = 1982 | pmid = 6757811 | doi = 10.1016/0149-7634(82)90030-6 | quote = 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]. }}</ref><ref name="Uyeno_1971">{{cite journal | vauthors = Uyeno ET | title = Relative potency of amphetamine derivatives and N,N-dimethyltryptamines | journal = Psychopharmacologia | volume = 19 | issue = 4 | pages = 381–387 | date = 1971 | pmid = 5565249 | doi = 10.1007/BF00404382 }}</ref> 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.<ref name="Brimblecombe_1975" /> 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.<ref name="Glennon_1982" />
Subsequent research assessed 6-hydroxy-DMT at the serotonin receptors ''in vitro''.<ref name="Sard_2005">{{cite journal | vauthors = Sard H, Kumaran G, Morency C, Roth BL, Toth BA, He P, Shuster L | title = SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist | journal = Bioorganic & Medicinal Chemistry Letters | volume = 15 | issue = 20 | pages = 4555–4559 | date = October 2005 | pmid = 16061378 | doi = 10.1016/j.bmcl.2005.06.104 }}</ref> It was found to have detectable but very low affinity for the serotonin 5-HT<sub>2</sub> receptors (K<sub>i</sub> ≥ 6,300–19,000{{nbsp}}nM).<ref name="Sard_2005" />
==Chemistry== ===Properties=== The predicted log P of 6-HO-DMT is 2.4.<ref name="PubChem">{{cite web | title=3-(2-(Dimethylamino)ethyl)-1H-indol-6-ol | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/15124 | access-date=5 November 2025}}</ref> For comparison, the predicted log P of psilocin (4-HO-DMT) is 2.1<ref name="PubChem-Psilocin">{{cite web | title=Psilocin | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/4980 | access-date=5 November 2025}}</ref> and of bufotenin (5-HO-DMT) is 1.2.<ref name="PubChem-Bufotenin">{{cite web | title=Bufotenine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/10257 | access-date=5 November 2025}}</ref>
===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.<ref name="Hearst_1962">{{cite journal | vauthors = Hearst E, Putney F, Szara S | title = Metabolism and behavioural action of psychotropic tryptamine homologues | journal = International Journal of Neuropharmacology | volume = 1 | issue = 1–3 | pages = 111–117 | date = 1962 | doi = 10.1016/0028-3908(62)90015-1 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=cbda9f12645473b959604c5f1babb5fe7b282dee | url-access = subscription }}</ref>
==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.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref><ref name="DEA2007">{{cite web | author=Drug Enforcement Administration | title=Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances | website=Federal Register | date=3 December 2007 | url=https://www.federalregister.gov/documents/2007/12/03/E7-23413/definition-of-positional-isomer-as-it-pertains-to-the-control-of-schedule-i-controlled-substances}}</ref>
==See also== * Substituted tryptamine * 13-Hydroxy-LSD
==References== {{Reflist}}
==External links== * [https://isomerdesign.com/pihkal/explore/5102 6-HO-DMT - Isomer Design]
{{Serotonin receptor modulators}} {{Tryptamines}}
{{DEFAULTSORT:Hydroxy-DMT, 6-}}
Category:N,N-Dialkyltryptamines Category:Dimethylamino compounds Category:Hydroxyarenes Category:Psychedelic drug metabolites Category:Serotonin receptor modulators