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

大麻成分（大麻素）的分子药理学、生化和毒理学研究——基于EBM的预防大麻滥用

• 批准号: 20590130
• 负责人: YAMAMOTO Ikuo
• 金额: $ 2.91万
• 依托单位: Kyushu University of Health and Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590130/
• 关键词: 大麻; カンナビノイド; アロマターゼ(CYP19); テトラヒドロカンナビノール(THC); カンナビジオール(CBD); カンナビノール(CBN); 芳香環化; ステロイド; 内分泌かく乱作用; アロマターゼ; 17β-ヒドロキシステロイド脱水素酵素(17β-HSD); ステロイド代謝; テトラヒドロカナビノール(THC); CYP19; 芳香化

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.

我们已经报道了大麻的三种主要成分，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学和毒理学作用。在存在研究中，我们通过CYP 19（芳香酶）检查了这些大麻素的代谢。作为结果，我们指出了8-羟基-CBN代谢物，其由THC芳构化和/或羟基化。同时，我们还研究了大麻素类化合物对CYP 19（芳香化酶）和17β-HSD（17β-羟基类固醇脱氢酶）代谢类固醇（雄酮、睾酮、TES和雌酮、E1）的影响。我们发现THC、CBD和CBN（50μM）分别抑制TES代谢为雌二醇（E2）的16%、60%和46%。THC、CBD和CBN分别抑制CYP 19将AND代谢为TES和E1代谢为E2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。

项目成果

Cannabidiol-2′,6′-Dimethyl Ether, a Cannabidiol Derivative, Is a Highly Potent and Selective 15-Lipoxygenase Inhibitor

• DOI: 10.1124/dmd.109.026930
• 发表时间: 2009-08-01
• 期刊: DRUG METABOLISM AND DISPOSITION
• 影响因子: 3.9
• 作者: Takeda, Shuso;Usami, Noriyuki;Watanabe, Kazuhito
• 通讯作者: Watanabe, Kazuhito

Δ9-Tetrahydrocannabinol and Its Major Metabolite Δ9-Tetrahydrocannabinol-11-oic Acid as 15-Lipoxygenase Inhibitors

• DOI: 10.1002/jps.22354
• 发表时间: 2011-03-01
• 期刊: JOURNAL OF PHARMACEUTICAL SCIENCES
• 影响因子: 3.8
• 作者: Takeda, Shuso;Jiang, Rongrong;Watanabe, Kazuhito
• 通讯作者: Watanabe, Kazuhito

大麻主成分(THC,CBD,CBN)のCYP19および17β-ヒドロキシステロイド脱水素酵素によるステロイド代謝に及ぼす阻害機作

大麻主要成分（THC、CBD、CBN）对CYP19和17β-羟基类固醇脱氢酶类固醇代谢的抑制机制

• 发表时间: 2010
• 作者: 宇佐見則行;岸信行;山本郁男;渡辺和人
• 通讯作者: 渡辺和人

大麻はなぜ怖いか?-含有成分の構造とその作用-

大麻为什么可怕？-其成分结构及其功效-

• 发表时间: 2009
• 期刊: 化学 64
• 作者: 山本郁男;宇佐見則行;井本真澄;渡辺和人
• 通讯作者: 渡辺和人

General of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone

小鼠肝微粒体大麻二酚和大麻二酚羟基醌代谢过程中活性氧的概况

• 发表时间: 2008
• 期刊: Life Sciences 83
• 作者: Noriyuki Usami;Ikuo Yamamoto;Kazuhito Watanabe
• 通讯作者: Kazuhito Watanabe