Endocrine disrupting effects of marijuana and its mechanism

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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.