Cannabinoids as Potent Inhibitors of Human CYP1 Enzymes

Abstract The three major phytocannabinoids, Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), cannabidiol (CBD), and cannabinol (CBN), are highly lipophilic compounds, and good substrates of liver microsomal drug-metabolizing enzymes. These cannabinoids are known to be efficiently metabolized by cytochrome P450 (CYP). Our research group recently conducted a systematic evaluation of the inhibitory potencies of the major phytocannabinoids toward recombinant human CYP enzymes. CYP1 enzymes were not critically involved in the metabolism of these cannabinoids by human liver microsomes, while the three major phytocannabinoids potently inhibited the catalytic activities of the human CYP1 enzymes, CYP1A1, CYP1A2, and CYP1B1. This review summarized the inhibition of human CYP1 enzymes by the major phytocannabinoids, as well as the significance of their inhibitory effects in drug interactions, and the development of chemopreventive agents.