Effects of chronic marijuana use on endothelial function

项目总结 这是一项临床观察性研究，将填补我们对大麻如何 使用和二手接触会影响心血管健康。大麻合法化的可能后果 是故意吸食大麻，以及非自愿的二手烟接触，在未来将大大增加 好几年了。虽然一些回溯性的人类关联研究未能找到明确的关联 除了吸食大麻和心血管疾病外，其他研究也表明，吸食大麻会增加 继发心肌梗死(MI)和心力衰竭的风险。目前尚不清楚这些不良影响是否 是由大麻或烟雾引起的。尽管如此，尽管公众意识到烟草烟雾是 尽管有害，但许多人仍然认为大麻烟是无害的。此外，对心血管的影响 在人体研究中，暴露于二手烟(SHS)的研究相对较少。的确有 越来越多的证据表明，主动吸食大麻和暴露于大麻SHS都会导致血管 内皮功能障碍。虽然内皮功能障碍是暂时的，但临床研究表明，不仅 吸烟者是否有内皮功能障碍，但反复暴露于SHS会导致慢性功能障碍 也是。因此，重要的是要确定人类是长期吸食主动大麻还是被动吸食大麻。 同样会导致内皮功能障碍。 这项提议的总体假设是，积极使用大麻或接触二手烟会导致 对人类的心血管不良后果。首要目标是通过测量以下各项来检验这一假设： 在其他健康的亚健康人群中，检测心血管风险的功能指标和循环生物标记物 在日常生活中经常主动或被动接触大麻的对象(此建议 不涉及使人类接触大麻)。其影响是，提高了对不利因素的理解 故意或非自愿接触大麻对心血管的影响将更好地促进个人健康 行为、医生对病人的建议、公共卫生政策决策、法律原则和潜力 大麻产业及其产品的监管。目标1是确定血管功能是否因 与烟草相关的其他健康个体的慢性主动或被动吸食大麻(年龄≤50) 吸烟者和避免接触烟草和大麻的人。目标2是确定这些慢性疾病 暴露条件会增加血液中心血管风险的生物标志物。目标3是确定是否培养了 在暴露个体的血清中培养的内皮细胞经历了与以下方面相关的不利功能变化 非使用者的血清，表明暴露于空气中可能导致血管功能受损 这些产品。

PROJECT SUMMARY This is a clinical observational study that will fill an important gap in our understanding of how marijuana use, and secondhand exposure, impact cardiovascular health. A likely consequence of marijuana legalization is that intentional smoking of cannabis, and involuntary secondhand exposure, will greatly increase in coming years. While some retrospective human association studies have failed to find clear-cut associations between marijuana smoking and cardiovascular disease, other studies have indicated that marijuana use increases the risk of subsequent myocardial infarction (MI) and heart failure. It is unclear whether these adverse effects are caused by the cannabinoids or the smoke. Nonetheless, despite public awareness that tobacco smoke is harmful, many people still assume that marijuana smoke is benign. Moreover, cardiovascular effects of secondhand smoke (SHS) exposure have remained relatively unexplored in human studies. There is increasing evidence in rats that both active marijuana smoking and marijuana SHS exposure causes vascular endothelial dysfunction. While the endothelial dysfunction is transient, clinical studies have shown that not only do tobacco smokers have endothelial dysfunction, but repeated exposures to SHS lead to chronic dysfunction as well. Therefore, it is important to determine in humans if chronic active or passive marijuana smoking similarly causes endothelial dysfunction. The overall hypothesis of this proposal is that active use of marijuana, or secondhand exposure, causes adverse cardiovascular consequences in humans. The overarching goal is to test this hypothesis by measur- ing a panel of functional indicators and circulating biomarkers of cardiovascular risk, in otherwise healthy sub- jects who are actively or passively exposed on a regular basis in their daily lives to cannabis (this proposal does not involve exposing humans to cannabis). The impact is that an improved understanding of the adverse cardiovascular effects of intentional or involuntary exposure to cannabis will better inform personal health behavior, advice of physicians to their patients, public health policy decisions, legal doctrines, and potential regulation of the cannabis industry and its products. Aim 1 is to determine if vascular function is impaired by chronic active or passive marijuana smoking in otherwise healthy individuals (age ≤50), relative to tobacco smokers and to people who avoid exposure to tobacco and marijuana. Aim 2 is to determine if these chronic exposure conditions increase biomarkers of cardiovascular risk in the blood. Aim 3 is to determine if cultured endothelial cells incubated in sera from exposed individuals undergo adverse functional changes relative to non-users’ sera, indicating potential mechanisms by which vascular function is being impaired by exposure to these products.