Mechanisms underlying inhibition of human cytochrome P450 enzymesby major phytocannabinoids

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental pharmacy
• Research Institution: Shinshu University (2012); Hokuriku University (2011)
• Principal Investigator: YAMAORI Satoshi 信州大学, 医学部附属病院, 准教授 (40360218)
• Project Period (FY): 2011 – 2012
• Keywords: 中毒学 / 異物代謝 / 分子毒性学

Research Abstract

Effects of three major phytocannabinoids, THC, CBD and CBN, onhuman cytochrome P450 (CYP) activities were investigated. THC, CBD and CBN inhibited manyCYP activities (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2J2,CYP3A4, CYP3A5, CYP3A7, CYP4F2, CYP4F3B, CYP4F12) to various extents. Inhibitions by THC,CBD and CBN were reversible (competitive, noncompetitive and mixed types) and/orirreversible depending on CYP isoforms examined.

Research Products

• [Journal Article] Significance of CYP2C9genetic polymorphism in inhibitoryeffect of Δ^9-tetrahydrocannabinol onCYP2C9 activity (2013)
  • Author(s): Satoshi Yamaori, Mika Kushihara, Kyoko Koeda, Ikuo Yamamoto, Kazuhito Watanabe
  • Journal Title: Forensic Toxicol. Volume: Vol.31 Pages: 70-75
  • DOI: DOI:10.1007/s11419-012-0148-3
  • Peer Reviewed
• [Journal Article] Comparison in thein vitro inhibitory effects of majorphytocannbinoids and polycyclicaromatic hydrocarbons contained inmarijuana smoke on cytochrome P450 2C9activity (2012)
  • Author(s): Satoshi Yamaori, Kyoko Koeda, MikaKushihara, Yui Hada, Ikuo Yamamoto,Kazuhito Watanabe
  • Journal Title: Drug Metab. Pharmacokinet. Volume: Vol.27 Pages: 294-300
  • DOI: DOI:10.2133/dmpk.DMPK-11-RG-107
  • Peer Reviewed
• [Journal Article] Cannabidiol, a major phytocannbinoids,as a potent atypical inhibitor forCYP2D6. (2011)
  • Author(s): Satoshi Yamaori, Yasuka Okamoto, IkuoYamamoto, Kazuhito Watanabe
  • Journal Title: Drug Metab. Dispos. Volume: Vol.39 Pages: 2049-2056
  • DOI: DOI:10.1124/dmd.111.041384
  • Peer Reviewed
• [Journal Article] Cannabidiol is apotent inhibitor of the catalyticactivity of cytochrome P450 2C19
  • Author(s): Rongrong Jiang, Satoshi Yamaori, Yasuka Okamoto, Ikuo Yamamoto, Kazuhito Watanabe
  • Journal Title: DrugMetab. Pharmacokinet. Volume: (in press)
  • DOI: DOI:10.2133/dmpk.DMPK-12-RG-129
  • Peer Reviewed
• [Presentation] 大麻主成分カンナビジオールは強力かつ非典型的な CYP2D6 阻害剤である (2012)
  • Author(s): 山折 大、岡本泰佳、大森 栄、山本郁男、渡辺和人
  • Organizer: 日本薬物動態学会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2012-11-20
• [Presentation] Inhibitory effects of major phytocannabinoids in marijuana on human drug-metabolizing cytochrome P450s and their possible mechanisms (2012)
  • Author(s): Satoshi Yamaori
  • Organizer: The International Association of Forensic Toxicologists
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2012-06-08
• [Presentation] 大麻主成分カンナビジオールによるCYP2C19 の阻害とその機構 (2012)
  • Author(s): 蒋 融融、山折 大、山本郁男、渡辺和人
  • Organizer: 日本薬学会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2012-03-30
• [Presentation] 大麻煙含有成分の CYP2C9 活性に対する影響 (2012)
  • Author(s): 山折 大、小枝恭子、山本郁男、渡辺和人
  • Organizer: 日本薬学会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2012-03-30
• [Presentation] Metabolism of cannabidiol by cytochrome P450s in human liver microsomes、International Cannabinoid Research Society (2011)
  • Author(s): Rongrong Jiang、 Satoshi Yamaori、 Shuso Takeda 、 Ikuo Yamamoto 、 Kazuhito Watanabe
  • Organizer: International Cannabinoid Research Society
  • Place of Presentation: Pheasant Run (IL、USA)
  • Year and Date: 2011-07-07
• [Presentation] Inhibitory mechanism of major phytocannabinoids on cytochrome P450 2D6 activity (2011)
  • Author(s): Satoshi Yamaori、Yasuka Okamoto、Ikuo Yamamoto 、 Kazuhito Watanabe
  • Organizer: International Cannabinoid Research Society
  • Place of Presentation: Pheasant Run (IL、USA)
  • Year and Date: 2011-07-07
• [Presentation] 大麻主成分カンナビノイドによるニコチン代謝酵素 CYP2A6 および CYP2B6の阻害機構 (2011)
  • Author(s): 山折 大、前田千佳子、山本郁男、渡辺和人
  • Organizer: 日本法中毒学会
  • Place of Presentation: 長崎大学中部講堂(長崎県)
  • Year and Date: 2011-06-11
• [Presentation] 大麻成分の代謝的相互作用とその個人差 (2011)
  • Author(s): 山折 大
  • Organizer: 日本法中毒学会
  • Place of Presentation: 長崎大学中部講堂(長崎県)
  • Year and Date: 2011-06-10