Endocrine disrupting effects of marijuana and its mechanism

通过对MCF-7人乳腺癌细胞的增殖试验，建立了E-Screen试验，利用雌激素对靶细胞的增殖作用来评价化学物质的雌激素活性。如果大麻和大麻类化合物表现为激动剂，那么它们应该模仿雌激素对MCF-7细胞增殖反应的影响。结果表明，在6.3-g/ml剂量范围内，THCA株大麻提取物对MCF-7细胞的增殖有促进作用，且呈剂量依赖关系，而CBDA株则不像THCA株那样促进MCF-7细胞增殖。但当剂量超过63g/ml时，细胞生长受到明显抑制。推测高浓度提取物的抗增殖作用可能与细胞毒性或细胞凋亡有关。所研究的大麻素(THC、CBD和CBN)和THC代谢物在0.01-1000 nM的浓度下没有表现出类似提取物的浓度依赖效应。用(ERE)3-Luc法检测大麻提取物和大麻烟提取物对报告基因转录活性的影响。这些结果表明，本实验中使用的大麻中的一种可变成分，而不是大麻中的大麻素，是该药物产生雌激素样作用的原因。例如，这可能是一种植物雌激素，是大麻及其部分纯化成分的一种不稳定的污染物。

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.