According toAlexander Shulgin in his bookTiHKAL (Tryptamines I Have Known and Loved), 4-MeO-DMT is not known to have been tested in humans.[6] However, theN,N-diethyl analogue4-MeO-DET has been tested in humans and was found to be completely inactive at doses of up to 30mgorally orsmoked.[6]
4-MeO-DMT producesserotonergic psychedelic-like effects in animals, including rodents and monkeys.[1][2][3][4][5] It has been found to disrupt object size discrimination performance in monkeys, suggesting that it may have psychedelic effects in humans.[1][9] However, whereas 5-MeO-DMT has greaterpotency thanbufotenin (5-HO-DMT), 4-MeO-DMT has lower potency thanpsilocybin (4-PO-DMT).[1] This may be due to the fact that thelipophilicity ofpsilocin is not importantly enhanced byO-methylation, in contrast to the case of bufotenin, which has associated limitations in terms ofblood–brain barrierpermeability.[1] Besides psilocin/psilocybin, 4-MeO-DMT is also less potent than 5-MeO-DMT.[2]
^abcdefgBrimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds".Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144.ISBN978-0-85608-011-1.OCLC2176880.OL4850660M.In contrast to the pronounced enhancement of hallucinogenic activity associated with methylation of the 5-hydroxyl group of bufotenin, 4-methoxy-N,N-dimethyltryptamine (4.26) is less potent than psilocybin. The respective ED50 values (µmoles/kg., i.p.) for disrupting size-discrimination performance in monkeys and swimming ability in rodents are 18·9 and 2·9 (Uyeno, 1969) and 20·1 and 8·7 (Uyeno, 1971). Perhaps these results reflect the differing lipid solubilities of the compounds, because bufotenin, 5-MeO-DMT, psilocin, and compound 4.26 have respective chloroform-water partition coefficients of 0·06, 3·30, 5·52, and 2·28 (Gessner and others, 1968). Clearly, little advantage in physico-chemical characteristics is gained by methylation of the 4-hydroxy group of psilocin compared to the 5-hydroxy group of bufotenin.
^abcGlennon RA, Young R, Benington F, Morin RD (February 1982). "Hallucinogens as discriminative stimuli: a comparison of 4-OMe DMT and 5-OMe DMT with their methythio counterparts".Life Sciences.30 (5):465–7.doi:10.1016/0024-3205(82)90463-5.PMID6801410.
^abKline TB, Benington F, Morin RD, Beaton JM (August 1982). "Structure-activity relationships in potentially hallucinogenic N,N-dialkyltryptamines substituted in the benzene moiety".Journal of Medicinal Chemistry.25 (8):908–13.doi:10.1021/jm00350a005.PMID7120280.
^abKline TB, Benington F, Morin RD, Beaton JM, Glennon RA, Domelsmith LN, Houk KN, Rozeboom MD (November 1982). "Structure-activity relationships for hallucinogenic N,N-dialkyltryptamines: photoelectron spectra and serotonin receptor affinities of methylthio and methylenedioxy derivatives".Journal of Medicinal Chemistry.25 (11):1381–3.doi:10.1021/jm00353a021.PMID6815326.
^abcShulgin, Alexander;Shulgin, Ann (September 1997).TiHKAL: The Continuation.Berkeley, California:Transform Press.ISBN0-9630096-9-9.OCLC38503252. "The 4-methyl ether of psilocin, 4-MeO-DMT, is especially appealing, in that it is a simple homologue of psilocin and it is quite stable. But the methyl group as an ether link lacks the lability of the phosphate or acetate esters, and it cannot be easily hydrolyzed off to form psilocin. The immediate homologue is 4-MeO-DET which is completely without action either orally or by smoking at dosages up to 30 mgs. [...] The 5-MeO-DMT has already been mentioned, and the remaining two would be 4-MeO-DMT and 4-MeO-DIPT. The former is a known compound but has not been measured in man. The latter is not a known compound."
^abcGlennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV (August 2000). "Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors".Drug Alcohol Depend.60 (2):121–132.doi:10.1016/s0376-8716(99)00148-9.hdl:11380/17721.PMID10940539.
^Uyeno ET (May 1969). "Alteration of a learned response of the squirrel monkey by hallucinogens".Int J Neuropharmacol.8 (3):245–253.doi:10.1016/0028-3908(69)90045-8.PMID4978723.
^Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA (January 1983). "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines".Eur J Pharmacol.86 (3–4):453–459.doi:10.1016/0014-2999(83)90196-6.PMID6572591.
^Glennon RA, Young R, Rosecrans JA, Kallman MJ (1980). "Hallucinogenic agents as discriminative stimuli: a correlation with serotonin receptor affinities".Psychopharmacology (Berl).68 (2):155–158.doi:10.1007/BF00432133.PMID6776558.
