4-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 30mg orally or smoked.

Interactions

Pharmacology

Pharmacodynamics

4-MeO-DMT has shown high affinity for several serotonin receptors, including the serotonin 5-HT1A receptor (Ki = 235nM), the serotonin 5-HT2A receptor (Ki = 68–1,300nM), and the serotonin 5-HT2C receptor (Ki = 340nM). 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 of about 3.53mg/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 3.47μmol/kg and about 2.7-fold lower potency than 5-MeO-DMT.

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

Legal status

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.

References

References

1. (1975). "Hallucinogenic Agents". Wright-Scientechnica.
2. (February 1982). "Hallucinogens as discriminative stimuli: a comparison of 4-OMe DMT and 5-OMe DMT with their methythio counterparts". Life Sciences.
3. (August 1982). "Structure-activity relationships in potentially hallucinogenic N,N-dialkyltryptamines substituted in the benzene moiety". Journal of Medicinal Chemistry.
4. (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.
5. (1984). "Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives". Raven Press.
6. {{CiteTiHKAL "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."
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9. (October 2025). "Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism". ACS Chem Neurosci.
10. (May 1969). "Alteration of a learned response of the squirrel monkey by hallucinogens". Int J Neuropharmacol.
11. (January 1983). "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines". Eur J Pharmacol.
12. (1980). "Hallucinogenic agents as discriminative stimuli: a correlation with serotonin receptor affinities". Psychopharmacology (Berl).
13. (March 1968). "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sci.
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16. [[Drug Enforcement Administration]]. (3 December 2007). "Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances".