Effects of chronic marijuana use on endothelial function

项目摘要 这是一项临床观察研究，将填补我们对大麻如何作用的理解中的一个重要空白 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 有意吸食大麻和非自愿的二手接触， 年虽然一些回顾性的人类关联研究未能找到明确的关联， 大麻吸烟和心血管疾病，其他研究表明，大麻使用增加 随后发生心肌梗死（MI）和心力衰竭的风险。目前尚不清楚这些不利影响是否 大麻素或烟雾引起的然而，尽管公众意识到烟草烟雾是 虽然大麻是有害的，但许多人仍然认为吸食大麻是无害的。此外， 二手烟（SHS）暴露在人类研究中仍然相对未被探索。有 越来越多的证据表明，在大鼠中，主动吸食大麻和大麻SHS暴露都会导致血管 内皮功能障碍虽然内皮功能障碍是短暂的，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导致慢性功能障碍 也因此，重要的是要确定在人类，如果慢性主动或被动吸食大麻 类似地导致内皮功能障碍。 这项建议的总体假设是，积极使用大麻，或二手接触，导致 对人类心血管的不良影响。最重要的目标是通过测量来检验这一假设- 在其他健康的亚健康人群中， 在日常生活中经常主动或被动接触大麻的人（本建议 不涉及将人类暴露于大麻）。其影响是，对不利因素的了解有所提高 有意或无意接触大麻的心血管影响将更好地告知个人健康 行为，医生对病人的建议，公共卫生政策决定，法律的学说，以及潜在的 对大麻产业及其产品的监管。目的1是确定是否血管功能受损， 在其他健康个体（年龄≤50岁）中，相对于烟草，慢性主动或被动吸食大麻 吸烟者和避免接触烟草和大麻的人。目的2是确定这些慢性 暴露条件会增加血液中心血管风险的生物标志物。目的3是确定是否培养 在来自暴露个体的血清中孵育的内皮细胞经历相对于 非使用者血清，表明暴露于 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.