Endogenous DMT

N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. Studies have investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. 

INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. 

A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. 

These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.

The first claimed detection of mammalian endogenous DMT was published in June 1965: German researchers F. Franzen and H. Gross report to have evidenced and quantified DMT, along with its structural analog bufotenin (5-HO-DMT), in human blood and urine. 

In an article published four months later, the method used in their study was strongly criticized, and the credibility of their results challenged.

Few of the analytical methods used prior to 2001 to measure levels of endogenously formed DMT had enough sensitivity and selectivity to produce reliable results.

Gas chromatography, preferably coupled to mass spectrometry (GC-MS), is considered a minimum requirement.

A study published in 2005 implements the most sensitive and selective method ever used to measure endogenous DMT: liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS) allows for reaching limits of detection (LODs) 12 to 200 fold lower than those attained by the best methods employed in the 1970s. 

The data summarized in the table below are from studies conforming to the abovementioned requirements (abbreviations used: CSF = cerebrospinal fluid; LOD = limit of detection; n = number of samples; ng/L and ng/kg = nanograms (10⁻⁹ g) per litre, and nanograms per kilogram, respectively):

DMT in body fluids and tissues (NB: units have been harmonized)

Species	Sample	Results
Human	Blood serum	< LOD (n = 66)
	Blood plasma	< LOD (n = 71) ♦  < LOD (n = 38); 1,000 & 10,600 ng/L (n = 2)
	Whole blood	< LOD (n = 20); 50–790 ng/L (n = 20)
	Urine	< 100 ng/L (n = 9)  ♦  < LOD (n = 60); 160–540 ng/L (n = 5)  ♦  Detected in n = 10 by GC-MS
	Feces	< 50 ng/kg (n = 12); 130 ng/kg (n = 1)
	Kidney	15 ng/kg (n = 1)
	Lung	14 ng/kg (n = 1)
	Lumbar CSF	100,370 ng/L (n = 1); 2,330–7,210 ng/L (n = 3); 350 & 850 ng/L (n = 2)
Rat	Kidney	12 &16 ng/kg (n = 2)
	Lung	22 & 12 ng/kg (n = 2)
	Liver	6 & 10 ng/kg (n = 2)
	Brain	10 &15 ng/kg (n = 2) ♦  Measured in synaptic vesicular fraction
Rabbit	Liver	< 10 ng/kg (n = 1)

A 2013 study found DMT in microdialysate obtained from a rat's pineal gland, providing evidence of endogenous DMT in the mammalian brain.

In 2019 experiments showed that the rat brain is capable of synthesizing and releasing DMT. These results raise the possibility that this phenomenon may occur similarly in human brains.