Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ⁹-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ⁹-THC. In mice, genistein blocked Δ⁹-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ⁹-THC-induced atherosclerosis.

流行病学研究表明，大麻会增加心血管疾病 (CVD) 的风险；然而，人们对该机制知之甚少。Δ ⁹ -四氢大麻酚 (Δ ⁹ -THC) 是大麻的精神活性成分，可与脉管系统中的大麻素受体 1 (CB1/CNR1) 结合并与 CVD 相关。英国生物银行的一项分析发现，大麻是心血管疾病的一个危险因素。我们发现吸食大麻会激活与 CVD 相关的炎性细胞因子。计算机虚拟筛选将染料木黄酮（一种大豆异黄酮）鉴定为假定的 CB1 拮抗剂。人诱导的多能干细胞来源的内皮细胞被用于模拟 Δ ⁹-THC 通过 NF-κB 信号传导诱导炎症和氧化应激。^{用 siRNA、CRISPR 干扰和染料木黄酮敲低 CB1 受体可减弱 Δ 9} -THC的作用。在小鼠中，染料木黄酮阻断了 Δ ⁹ -THC 诱导的内皮功能障碍，减少了动脉粥样硬化斑块，并且对中枢神经系统的渗透最小。Genistein 是一种 CB1 拮抗剂，可减轻 Δ ⁹ -THC 诱导的动脉粥样硬化。