4-MeO-DMT

4-MeO-DMT
Clinical data
Other names4-OMe-DMT; 4-Methoxy-DMT; 4-Methoxy-N,N-dimethyltryptamine; O-Methylpsilocin; PSOM
Drug classSerotonin receptor modulator
Identifiers
  • 2-(4-Methoxy-1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H18N2O
Molar mass218.300 g·mol−1
3D model (JSmol)
  • CN(C)CCC1=CNC2=CC=CC(OC)=C21
  • InChI=1S/C13H18N2O/c1-15(2)8-7-10-9-14-11-5-4-6-12(16-3)13(10)11/h4-6,9,14H,7-8H2,1-3H3 checkY
  • Key:HFYHBTWTJDAYGW-UHFFFAOYSA-N checkY
  (verify)

4-MeO-DMT, or 4-methoxy-DMT, also known as 4-methoxy-N,N-dimethyltryptamine or as O-methylpsilocin (PSOM), is a serotonin receptor modulator and possible psychedelic drug of the tryptamine and 4-hydroxytryptamine families. It is the O-methylated analogue of psilocin (4-HO-DMT) and a positional isomer of 5-MeO-DMT.

Use and effects

According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), 4-MeO-DMT is not known to have been tested in humans. However, the N,N-diethyl analogue 4-MeO-DET has been tested in humans and was found to be completely inactive at doses of up to 30 mg orally or smoked.

Interactions

Pharmacology

Pharmacodynamics

4-MeO-DMT activities
TargetAffinity (Ki, nM)
5-HT1A235 (Ki)
352 (EC50Tooltip half-maximal effective concentration)
103% (EmaxTooltip maximal efficacy)
5-HT2A68–1,300 (Ki)
21 (EC50)
76% (Emax)
5-HT2B9 (EC50)
58% (Emax)
5-HT2C340 (Ki)
4 (EC50)
100% (Emax)
SERTTooltip Serotonin transporter 903 (IC50)
NETTooltip Norepinephrine transporter, DATTooltip Dopamine transporter >10,000
Notes: The smaller the value, the more avidly the drug interacts with the site. Sources:

4-MeO-DMT has shown high affinity for several serotonin receptors, including the serotonin 5-HT1A receptor, the serotonin 5-HT2A receptor, and the serotonin 5-HT2C receptor. Compared to 5-MeO-DMT, 4-MeO-DMT had similar affinity for the serotonin 5-HT2A receptor, but showed much lower affinity (21-fold) for the serotonin 5-HT1A receptor. The drug shows pronounced biased agonism at the serotonin 5-HT2C receptor.

4-MeO-DMT produces serotonergic psychedelic-like effects in animals, including rodents and monkeys. It has been found to disrupt object size discrimination performance in monkeys, suggesting that it may have psychedelic effects in humans. However, whereas 5-MeO-DMT has greater potency than bufotenin (5-HO-DMT), 4-MeO-DMT has lower potency than psilocybin (4-PO-DMT). This may be due to the fact that the lipophilicity of psilocin is not importantly enhanced by O-methylation, in contrast to the case of bufotenin, which has associated limitations in terms of blood–brain barrier permeability. Besides psilocin/psilocybin, 4-MeO-DMT is also less potent than 5-MeO-DMT.

4-MeO-DMT fully substituted for DOM in rodent drug discrimination tests, with an ED50Tooltip median effective dose of about 3.53 mg/kg and about 3-fold lower potency than 5-MeO-DMT. 4-MeO-DMT also substituted for 5-MeO-DMT in rodent drug discrimination tests, with an ED50 of 3.47 μmol/kg and about 2.7-fold lower potency than 5-MeO-DMT. Despite its activity in drug discrimination tests however, 4-MeO-DMT fails to produce the head-twitch response in rodents. This may in part be related to the drug's unusually potent serotonin 5-HT1A receptor agonism.

Chemistry

Analogues

Analogues of 4-MeO-DMT include dimethyltryptamine (DMT), 4-methoxytryptamine (4-MT or 4-MeO-T), psilocin (4-HO-DMT), 4-AcO-DMT (psilacetin), 4-MeO-DET, 4-MeO-DiPT, 4-MeO-MiPT, 4-methyl-DMT, 5-MeO-DMT, 6-MeO-DMT, and 7-MeO-DMT, among others.

History

4-MeO-DMT was first described in the scientific literature by at least 1968.

Society and culture

Canada

4-MeO-DMT is not a controlled substance in Canada.

United States

In the United States, 4-MeO-DMT is a Schedule I controlled substance as it is a positional isomer of 5-MeO-DMT.

See also

References

  1. 1 2 3 4 5 6 7 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. 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.
  2. 1 2 3 Glennon 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. PMID 6801410.
  3. 1 2 Kline 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. PMID 7120280.
  4. 1 2 Kline 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. PMID 6815326.
  5. 1 2 3 Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237.
  6. 1 2 3 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. "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."
  7. 1 2 3 Glennon 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. PMID 10940539.
  8. 1 2 3 Lyon RA, Titeler M, Seggel MR, Glennon RA (January 1988). "Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens". Eur J Pharmacol. 145 (3): 291–297. doi:10.1016/0014-2999(88)90432-3. PMID 3350047. Archived from the original on 21 April 2024.
  9. 1 2 3 Glatfelter GC, Schalk SS, Walther D, Maitland AD, Gonzalez NR, Partilla JS, Anas NA, Chadeayne AR, Naeem M, Manke DR, McCorvy JD, Baumann MH (May 2026). "Serotonin Transporter Blockade Reduces the Psychedelic-Like Effects of 4-Methoxy-N-methyl-N-isopropyltryptamine and Related Analogs". ACS Chem Neurosci. doi:10.1021/acschemneuro.6c00083. PMID 42200433.
  10. ↑ Bonniwell EM, Alabdali R, Hennessey JJ, McKee JL, Cavalco NG, Lammers JC, Moore EJ, Franchini L, Orlandi C, McCorvy JD (October 2025). "Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism". ACS Chem Neurosci. 16 (19): 3899–3914. doi:10.1021/acschemneuro.5c00647. PMC 12629614. PMID 40944639.
  11. ↑ 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. PMID 4978723.
  12. ↑ 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. PMID 6572591.
  13. ↑ 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. PMID 6776558.
  14. ↑ Gessner PK, Godse DD, Krull AH, McMullan JM (March 1968). "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sci. 7 (5): 267–277. doi:10.1016/0024-3205(68)90200-2. PMID 5641719.
  15. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. 5 December 2025. Retrieved 20 January 2026.
  16. ↑ "Lists of Scheduling Actions Controlled Substances Regulated Chemical" (PDF). deadiversion.usdoj.gov. Retrieved 8 April 2023.
  17. ↑ Drug Enforcement Administration (3 December 2007). "Definition of "Positional Isomer" as It Pertains to the Control of Schedule I Controlled Substances". Federal Register.