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

Research Project

Project/Area Number 20590130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionKyushu University of Health and Welfare

Principal Investigator

YAMAMOTO Ikuo  Kyushu University of Health and Welfare, 薬学部, 教授 (50069746)

Co-Investigator(Kenkyū-buntansha) 宇佐見 則行  奥羽大学, 薬学部, 准教授 (60257483)
井本 真澄  九州保健福祉大学, 薬学部, 助手 (90369174)
Co-Investigator(Renkei-kenkyūsha) USAMI Noriyuki  奥羽大学, 薬学部, 准教授 (60257483)
Research Collaborator IMOTO Masumi  第一薬科大学, 助教 (90369174)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords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
Research Abstract

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.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (6 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Δ^9-tetrahydrocannabi- nol and its major metabolite Δ^9-tetra- hydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.2010

    • Author(s)
      Takeda S, Jiang R, Aramaki H, Imoto M, Toda A, Eyanagi R, Amamoto T, Yamamoto I, Watanabe K
    • Journal Title

      J.Pharm.Sci.

    • Related Report
      2010 Final Research Report
  • [Journal Article] Δ^9-tetrahydrocannabinol and its major metabolite Δ^9-tetrahydrocannabinol-11-oic acid as 15-lipoxygenase inhibitors.2010

    • Author(s)
      Takeda S, Jiang R, Aramaki H, Imoto M, Toda A, Eyanagi R, Amamoto T, Yamamoto I, Watanabe K.
    • Journal Title

      J.Pharm.Sci.

      Volume: 100 Pages: 1206-1211

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes.2010

    • Author(s)
      Yamaori S, Kushihara M, Yamamoto I, Watanabe K.
    • Journal Title

      Biochem.Pharmacol.

      Volume: 79(11) Pages: 1691-1698

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大麻はなぜ怖いか?-含有成分の構造とその作用-2009

    • Author(s)
      山本郁男、宇佐見則行、井本真澄、渡辺和人
    • Journal Title

      化学 64

      Pages: 31-37

    • NAID

      40016594142

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cannabidiol-2',6'-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor2009

    • Author(s)
      Shuso Takeda, Noriyuki Usami, Ikuo Yamamoto, Kazuhito Watanabe
    • Journal Title

      Drug Metab.Dispos 37

      Pages: 1733-1737

    • Related Report
      2010 Final Research Report
  • [Journal Article] Modulation of Δ^9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase2009

    • Author(s)
      Shuso Takeda, Ikuo Yamamoto, Kazuhito Watanabe
    • Journal Title

      Toxicology 259

      Pages: 25-32

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cannabidiol-2',6'-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor.2009

    • Author(s)
      Shuso Takeda, Noriyuki Usami, Ikuo Yamamoto, Kazuhito Watanabe
    • Journal Title

      Drug Metab. Dispos. 37

      Pages: 1733-1737

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of Δ^9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase.2009

    • Author(s)
      Shuso Takeda, Ikuo Yamamoto, Kazuhito Watanabe
    • Journal Title

      Toxicology 259

      Pages: 25-32

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大麻はなぜ怖いか? -含有成分の構造とその作用-2009

    • Author(s)
      ○山本郁男, 宇佐見則行, 井本真澄, 渡辺和人
    • Journal Title

      化学 64

      Pages: 31-37

    • NAID

      40016594142

    • Related Report
      2008 Annual Research Report
  • [Journal Article] General of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone2008

    • Author(s)
      Noriyuki Usami、Ikuo Yamamoto、Kazuhito Watanabe
    • Journal Title

      Life Sciences 83

      Pages: 717-724

    • Related Report
      2010 Final Research Report
  • [Journal Article] General of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone2008

    • Author(s)
      Noriyuki Usami, Ikuo Yamamoto, Kazuhito Watanabe
    • Journal Title

      Life Sciences 83

      Pages: 717-724

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] カンナビノイド(THC、CBD、CBN)の内分泌かく乱物質作用-カンナビノイドの芳香環化とステロイド代謝阻害2011

    • Author(s)
      山本郁男、宇佐見則行、岸信行、渡辺和人
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 大麻主成分(THC,CBD,CBN)のヒトCYP19による性ステロイドホルモン代謝阻害機作2011

    • Author(s)
      宇佐見則行、岸信行、渡辺和人、山本郁男
    • Organizer
      日本法中毒学会第30年会
    • Place of Presentation
      長崎
    • Related Report
      2010 Final Research Report
  • [Presentation] 大麻主成分(THC、CBD、CBN)のCYP19によるステロイド代謝の阻害2010

    • Author(s)
      山本郁男、宇佐見則行、井本真澄、岸信行、渡辺和人
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 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2010

    • Author(s)
      宇佐見則行、岸信行、山本郁男、渡辺和人
    • Organizer
      日本法中毒学会第29年会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ヒトCYP19による主要大麻成分の代謝2009

    • Author(s)
      宇佐見則行、井本真澄、岸信行、山本郁男、渡辺和人
    • Organizer
      日本法中毒学会第28年会
    • Place of Presentation
      北陸大学(石川県)
    • Year and Date
      2009-06-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒトCYP19による主要大麻成分の代謝2009

    • Author(s)
      宇佐見則行、井本真澄、岸信行、山本郁男、渡辺和人
    • Organizer
      日本法中毒学会第28年会
    • Place of Presentation
      金沢
    • Related Report
      2010 Final Research Report
  • [Book] マリファナは怖い~乱用薬物~(改訂版)2009

    • Author(s)
      山本郁男
    • Publisher
      薬事日報社
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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