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KMID : 0043320050280121365
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Archives of Pharmacal Research
2005 Volume.28 No. 12 p.1365 ~ p.1375
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Antiestrogenic Effects of Marijuana Smoke Condensate and Cannabinoid Compounds
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Lee Soo-Yeun
Oh Seung-Min
Lee Sang-Ki
Jeong Gyu-Hyeok
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Abstract
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The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., -tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-Odeethylase (EROD) assay, the aromatase assay, and the 17-estradiol () metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.
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KEYWORD
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Marijuana, Cannabinoids, Drug abuse, Antiestrogenic effects, Polycyclic aromatic hydrocarbons (PAHs)
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