Effects of chronic marijuana use on endothelial function

长期吸食大麻对内皮功能的影响

• 批准号: 10636493
• 负责人: MATTHEW Lawrence SPRINGER
• 金额: $ 70.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636493
• 关键词: Acute; Address; Adverse effects; Age; Awareness; Benign; Biochemical; Biological Markers; Blood; Blood Pressure; Blood Vessels; Cannabinoids; Cannabis; Cannabis policy; Cardiovascular Diseases; Cardiovascular system; Cells; Chemicals; Chronic; Clinical; Clinical Research; Electrocardiogram; Endothelial Cells; Endothelium; Exposure to; Fibrosis; Functional disorder; Goals; Health; Health Policy; Health behavior; Heart failure; Human; Impairment; Incubated; Individual; Industry; Inflammation; Lead; Legal; Marijuana; Marijuana Smoking; Measures; Mediating; Medicine; Myocardial Infarction; Observational Study; Oxidative Stress; Patients; Permeability; Persons; Pharmaceutical Preparations; Physicians; Physiologic pulse; Plants; Platelet aggregation; Poison; Public Health; Rattus; Recreation; Risk; Smoke; Smoking; Testing; Time; Tissues; Tobacco; Tobacco smoke; Tube; cardiovascular effects; cardiovascular health; cardiovascular risk factor; circulating biomarkers; endothelial dysfunction; environmental tobacco smoke; environmental tobacco smoke exposure; exposed human population; functional disability; improved; marijuana legalization; marijuana smoke; marijuana use; recruit; response; secondhand cannabis smoke; tobacco exposure; tobacco smokers; vascular endothelial dysfunction

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.

项目概要 这是一项临床观察研究，将填补我们对大麻如何影响理解的一个重要空白。 使用和二手接触会影响心血管健康，这是大麻合法化的一个可能后果。 有意吸食大麻和非自愿二手接触将大大增加 尽管一些回顾性的人类关联研究未能发现两者之间的明确关联。 吸食大麻与心血管疾病有关，其他研究表明，吸食大麻会增加 随后发生心肌梗死 (MI) 和心力衰竭的风险尚不清楚。 尽管公众意识到烟草烟雾是由大麻素或烟雾引起的。 有害，许多人仍然认为吸大麻是良性的，而且对心血管有影响。 在人类研究中，二手烟（SHS）暴露尚未得到探索。 越来越多的证据表明，在大鼠中主动吸食大麻和接触大麻二手烟都会导致血管病变 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，不仅如此。 吸烟者是否有内皮功能障碍，但反复接触二手烟会导致慢性功能障碍 因此，确定人类是否长期主动或被动吸食大麻也很重要。 同样导致内皮功能障碍。 该提案的总体假设是，积极使用大麻或二手接触会导致 总体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，研究一组功能指标和心血管风险循环生物标志物 在日常生活中定期主动或被动接触大麻的对象（该提案 不涉及使人类接触大麻）。其影响是加深了对大麻的不利影响的了解。 有意或非自愿接触大麻对心血管的影响将更好地影响个人健康 行为、医生给患者的建议、公共卫生政策决定、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受到损害。 相对于烟草，健康个体（年龄≤50岁）长期主动或被动吸食大麻 吸烟者和避免接触烟草和大麻的人的目标 2 是确定这些慢性病是否存在。 暴露条件会增加血液中心血管风险的生物标志物，目标 3 是确定是否进行培养。 在暴露个体的血清中孵育的内皮细胞会发生相对于 非使用者血清，表明血管功能因暴露而受损的潜在机制 这些产品。