6-Hydroxy-DMT

6-Hydroxy-DMT, also known as 6-hydroxy-N,N-dimethyltryptamine, is a serotonin receptor modulator of the tryptamine family. It is a major metabolite of the psychedelic drug dimethyltryptamine (DMT) in rodents but a minor metabolite of DMT in humans. It is the 6-hydroxy analogue of DMT and a positional isomer of bufotenin (5-hydroxy-DMT) and psilocin (4-hydroxy-DMT).

The drug was completely inactive in terms of psychoactive and autonomic effects at doses of 0.75 to 1 mg/kg (~53–70 mg for a 70-kb person) by intramuscular injection in humans. The drug was said to be indistinguishable from placebo. Conversely, DMT produced strong hallucinogenic effects at the same doses. However, 6-hydroxy-DMT has been found to produce pharmacological effects in animals, albeit with diminished potency compared to DMT. 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. 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.

Subsequent research assessed 6-hydroxy-DMT at the serotonin receptors in vitro. It was found to have detectable but very low affinity for the serotonin 5-HT₂ receptors (K_i ≥ 6,300–19,000 nM).

6-Hydroxy-DMT was first described in the scientific literature by at least 1962.