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

我们已经报道了大麻中三种主要成分THC（四氢大麻酚）、CBD（大麻二酚）和CBN（大麻酚）的代谢与这些大麻素的药理和毒理学作用的关系。在存在的研究中，我们检查了这些大麻素的代谢CYP19（芳香化酶）。结果，我们发现了8-羟基- cbn代谢物，它是由四氢大麻酚芳香化和/或羟基化的。此外，通过GC/MS方法证实了CYP19由THC和CBD形成CBN。另一方面，我们研究了这些大麻素对CYP19（芳香化酶）和17β-HSD （17β-羟基类固醇脱氢酶）代谢类固醇（雄酮，AND，睾酮，TES和雌酮，E1）的影响。我们发现THC， CBD和CBN （50μM）分别抑制了16%，60%和46%的TES对雌二醇（E2）的代谢。四氢大麻酚、CBD和CBN分别抑制了CYP19对TES和E1对E2的代谢约20%。这一结果不仅表明这些大麻素与雌激素受体的相互作用，而且表明大麻成分包括其代谢物的内分泌干扰物样作用。

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.