The psychedelic compound N,N-dimethyltryptamine (DMT) is produced naturally in mammals, but whether it is made in the brain was unclear. This study found that the enzymes needed to synthesize DMT are present in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans. In rat brain tissues, the two key enzymes were found together, unlike in peripheral tissues. DMT concentrations in the cerebral cortex of behaving rats were similar to those of neurotransmitters like serotonin. DMT levels in the visual cortex rose significantly after cardiac arrest, even without the pineal gland. These findings indicate the rat brain can synthesize and release DMT at neurotransmitter-like levels, suggesting human brains might do the same.
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.