Cannabinoids apparently interfere with the metabolism of biogenic amines in the brain, indicating that the biogenic amine system is involved in the psychomimetic effect of hashish. The effect of Δ 1 -tetrahydrocannabinol (Δ 1 -THC), cannabidiol (CBD) and hashish extract on monoamine oxidase (MAO) from porcine brain mitochondria was therefore studied, using several substrates including amines of biological importance, such as serotonin, dopamine and tryptamine. While Δ 1 -THC and hashish extract inhibited MAO activity. to an extent varying according to the substrate, CBD was innocuous or only slightly inhibitory—in correspondence with the psychomimetic potency. Phospholipids associated with MAO were essential for the inhibition of the oxidase activity by Δ 1 -THC. In enzyme preparations from which the phospholipids were extracted, the sensitivity to Δ 1 -THC essentially disappeared. Sensitivity could be regained specifically upon addition of phosphatidylcholine. It is suggested that the phospholipids of the MAO complex function as the site of interaction with the Cannabinoids, leading to the observed changes in MAO activity. The differential effect of the Cannabinoids support the conclusion that MAO plays a central role in mediating the psychomimetic effect of hashish.
