A comparison of the brain levels (micog/g wet weight of tissue) of the hallucinogen N,Ndimethyltryptamine (DMT) and its deuterated analog a,a,b,b-tetradeutero-DMT (D4DMT) as a function of time and dose is reported. It was observed that the presence of deuterium in the (alpha-and beta-positions of the ethylamine side-chain led to a potentiation of the level of DMT in brain. Strikingly different dynamics of uptake and clearance were also noted. We propose that these results are due to a primary kinetic isotope effect, illustrating the importance of the cu-position in the metabolism of DMT.