Inhibition of Rat Brain Protein and Nucleic Acid Synthesis by Cannabinoids In Vitro

The effect of Δ 9 -tetrahydrocannabinol (THC), cannabidiol, and cannabigerol on some metabolic processes in infant and adult rat brain cortex slices was studied in vitro. With L-leucine-U- 14 C as the tracer substrate, the incorporation of radioactivity into the protein and nucleic acid fractions was significantly inhibited by THC. The oxygen consumption of the slices, the uptake of L-leucine into the slices, and the evolution of 14 CO 2 were, however, unaffected by THC. Cannabidiol was comparable in activity to THC but cannabigerol was less active. The pattern of inhibition by THC was also observed when the rat brain cortex slices were stimulated by 100 mM K + or 10 μM protoveratrine. THC also brought about a significant decrease in the incorporation of uridine-2- 14 C into the nucleic acid fraction of infant and adult rat brain cortex slices. There was a decreased formation of uridine nucleotides in the presence of THC and an increase in uridine and uracil in the low molecular weight fraction. Experiments with THC-2,4- 14 C established that there was rapid uptake and a concentration of radioactivity in the incubated brain tissue.