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Endocrine disrupting effects of marijuana and its mechanism

Research Project

Project/Area Number 13672353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionHokuriku University

Principal Investigator

WATANABE Kazuhito  Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 薬学部, 教授 (30113038)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Ikuo  Kyushu University of Health and Welfare, School of Pharmaceutical Sciences, Department of Hygienic Chemistry, Professor, 保健科学部, 教授 (50069746)
FUNAHASHI Tatsuya  Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Hygienic Chemistry, Research Associate, 薬学部, 助手 (60343646)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordsmarijuana / Endocrine disrupting chemical / estrogen / MCF-7 / cannabinoid / reporter gene assay / 細胞毒性 / レポータージーンアッセイ法 / 大麻抽出物 / CBDA種 / 内分泌攪乱作用
Research Abstract

The proliferation assay of MCF-7 human breast cancer cells, E-SCREEN assay has been developed to assess the estrogenicity of chemicals using the proliferative effect of estrogens on their target cells. If marijuana and cannabinoids behave as agonists, then they should mimic the effects of estradiol on the proliferative response in MCF-7 cells. The present study demonstrated that at a dose of up to 6.3 □g/ml, extract of THCA strain marijuana stimulated the proliferation of MCF-7 cells in a dose-dependent manner, while that of CBDA strain did not accelerate such as the THCA strain. However, at a dose of more than 63 □g/ml, the cell growth was significantly inhibited. It was presumed that the anti-proliferative effect at the high concentration of Extract was due to toxicity or to apoptosis of cells. The cannabinoids (THC, CBD and CBN) and THC metabolites examined did not show concentration-dependent effects such as the extract at the concentration of 0.01 to 1000 nM. Marijuana extracts and marijuana smoke extracts stimulated transcriptional activity of reporter gene assay using (ERE)3-Luc. These results suggest that a variable component of marijuana other than cannabinoids used in this experiment is responsible for the estrogen-like effects of this drug. This could, for example, be a phytoestrogen that is an inconstant contaminant of marijuana and its partially purified components.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] I.Yamamoto, E.Motoya, T.Matsunaga, K.Arizono, K.Watanabe: "Marijuana constituents may act as endocrine disrupting chemicals"Proceeding of TIAFT 2001. 304-311 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Watanabe, T.Matsunaga, T.Kimura, T.Funahashi, Y.Funae, T.Ohshima, I.Yamamoto: "Major cytochrome P450 responsible for microsomal aldehyde oxygenation of 11-oxo-delta-8-tetrahydrocannabinol and 9-anthraldehyde in human liver"Drug Metab. Pharmacokin.. 17(6). 516-521 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Matsunaga, H. Tanaka, S. Higuchi, K. Shibayama, N. Kishi, K. Watanabe and I. Yamamoto: "Oxidation mechanism of 7-hydroxy-delta-8-tetrahydrocannabinol and 8-hydroxfy-delta-9-tetrahydrocannabinol to the corresponding ketones by CYP3A11"Drug Metab. Dispos.. 29. 1485-1491 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] I. Yamamoto, E. Motoya, T. Matsunaga, K. Arizono and K. Watanabe: "Marijuana constituents may act as endocrine disrupting chemicals"Proceeding of TIAFT. 2001. 304-311 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Matsunaga, Y. Iwawaki, A. Komura, K. Watanabe, T. Kageyama and I. Yamamoto: "Monkey hepatic microsomal alcohol oxygenase : purification and characterization of a cytochrome P450 enzyme catalyzing the stereoselective oxidation of 7-alfa- an 7-beta-hydroxy-delta-8-tetrahydrocannabinol to 7-oxo-delta-8-tetrahydrocannabinol."Drug Metab. Pharmacokin.. 17. 516-521 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Watanabe, T. Matsunaga, T. Kimura, T. Funahashi, Y. Funae, T. Ohshima and I. Yamamoto: Biol. Pharm. Bull.. 25. 42-47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] I.Yamamoto, E.Motoya, T.Matsunaga, K.Arizono, K.Watanabe: "Marijuana constituents may act as endocrine disrupting chemicals"Proceeding of TIAFT 2001. 304-311 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Watanabe, T.Matsunaga, T.Kimura, T.Funahashi, Y.Funae, T.Ohshima, I.Yamamoto: "Major cytochrome P450 responsible for microsomal aldehyde oxygenation of 11-oxo-delta-8-tetrahydrocannabinol and 9-anthraldehyde in human liver"Drug Metab.Pharmacokin.. 17(6). 516-521 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Matsunaga, H.Tanaka, S.Higuchi, K.Shibayaina, N.Kishi, K.Watanabe, I.Yamamoto: "Oxidation mechanism of 7-hydroxy-delta-8-tetrahydrocannabinol and 8-hydroxy-delta-9-tetrahydrocannabinol to the corresponding ketones by CYP3A11"Drug Metab. Dispos.. 29(11). 1485-1491 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Matsunaga, Y.Iwawaki, A.Komura, K.Watanabe, T.Kageyama, I.Yamamoto: "Monkey hepatic microsornal alcohol oxygenase : purification and characterization of a cytochrome P450 enzyme catalyzing the stereoselective oxidation of 7-alfa-an 7-beta-hydroxy-delta-8-tetrahydrocannabinol to 7-oxo-delta-8-tetrahydrocannabinol"Biol. Pharm. Bull.. 25(1). 42-47 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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