Indolethylamine N-methyltransferase (INMT) is an enzyme known for producing the psychedelic compound DMT in mammalian brains. Researchers created INMT-knockout rats to determine whether INMT is necessary for DMT production. Brain and lung tissues from both normal and INMT-knockout rats showed equal levels of tryptamine-dependent activity, but the resulting products were neither NMT nor DMT. Rat INMT alone was also insufficient for producing NMT or DMT. These findings indicate an alternative enzymatic pathway for DMT biosynthesis exists in rats, motivating further investigation into how mammals produce DMT naturally.
Intravenous DMT in rats caused dose-dependent increases in serotonin and dopamine in the medial prefrontal and somatosensory cortices, along with changes in brain wave patterns: reduced theta and low gamma power, increased delta, medium gamma, and high gamma power, and altered functional connectivity. All doses produced head twitch responses, most after the low dose. For the first time, endogenous DMT was measured in these cortical sites at levels comparable to serotonin and dopamine, suggesting a physiological role for the compound. The findings point to shared mechanisms with other psychedelics and support DMT's potential for treating psychiatric disorders.