Effect of delta9-tetrahydrocannabinol on mitochondrial NADH-oxidase activity

Delta9-Tetrahydrocannabinol (delta9-THC), the active ingredient of marihuana was found to be a highly effective inhibitor in vitro of the NADH-oxidase activity of rat brain and heart mitochondria. The degree of inhibition of the enzyme system obtained from rat brain tissue varied with the region from which it was derived as follows, in the presence of 10(-5) M delta9-THC: hypothalamus plus thalamus plus midbrain, 73 +/- 4%; cerebellum, 66 +/- 4%; medulla oblongata plus pons, 63 +/- 6%; cerebral cortex, 50 +/- 8%. The same concentration inhibited rat heart NADH-oxidase activity 69 +/- 9%. Inhibition of NADH-oxidase activity by a corresponding concentration of deoxycorticosterone was significantly less in all tissue preparations tested, ranging from 11% to 26%. The inhibition of delta9-THC appeared to be competitive and near the amytal-sensitive site of the electron transport system. Suggestive evidence was also obtained for a second site of action, above the cytochrome c site.