The molecular pharmacological, biochemical and toxicological studies on the marihuana constituents (cannabinoids)-for the prevention of abused marihuana based on EBM

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We have reported the metabolism of three major constituents of marijuana, THC (tetrahydrocannabinol), CBD (cannabidiol) and CBN (cannabinol) in relation to the pharmacological and toxicological effects of these cannabinoids so far. In the presence study, we examined the metabolism of these cannabinoids by CYP19 (aromatase). As results, we indicated the 8-hydroxy-CBN metabolite, which is aromatized and/or hydroxylated from THC. Farther, the formation of CBN from THC and CBD by CYP19 was confirmed by GC/MS methods.On the other hands, we examined the effects of these cannabinoids on the metabolism of steroids (androsterone ; AND, testosterone ; TES and estrone; E1) by CYP19 (aromatase) and 17β-HSD (17β-hydroxysteroid dehydrogenase). We found that THC, CBD and CBN (50μM) inhibited 16, 60 and 46%, respectively, the metabolism of TES to estradiol (E2). The metabolism of AND to TES and E1 to E2 by CYP19 were inhibited about 20% with THC, CBD and CBN, respectively. This result suggests not only the interactions of these cannabinoids with the estrogen receptor, but also the endocrine disruptor-like effects of the marijuana constituents including their metabolites.