4-MeO-DMT

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.

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.

4-MeO-DMT has shown high affinity for several serotonin receptors, including the serotonin 5-HT_1A receptor (K_i = 235 nM), the serotonin 5-HT_2A receptor (K_i = 68–1,300 nM), and the serotonin 5-HT_2C receptor (K_i = 340 nM). Compared to 5-MeO-DMT, 4-MeO-DMT had similar affinity for the serotonin 5-HT_2A receptor, but showed much lower affinity (21-fold) for the serotonin 5-HT_1A 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.

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, 5-MeO-DMT, 6-MeO-DMT, and 7-MeO-DMT, among others.

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

In the United States 4-MeO-DMT is a Schedule 1 controlled substance as it is a positional isomer of 5-MeO-DMT.