Molecular mechanism for interaction of major cannabinoids with enzyme system

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Metabolic interaction and cell toxicity of major constituents of marijuana were studied and the following points were clarified. (1) Major CYP enzymes involved in the metabolism THC with mouse brain microsomes. (2) Major CYP enzymes involed in the metabolism of cannabidiol with human liver microsomes. (3) Inhibitory and inductive effects of major cannabinoids on human liver CYP enzymes. (4) Mechanisms of THC to induce cell toxicity (J774-1 cells) and stimulation of cell proliferation (MCF-7 cells). (5) Selective inhibition of cyclooxygenase-2 by cannabidiolic acid ; selective inhibition of 5-lipoxygenase by CBD-dimethylether ; Potent inhibition of 15-lipoxygenase by tetrahydrocannabinol and its major urinary metabolite.