The Effects of Cannabinoids and Route of Cannabis Administration on Subclinical Cardiovascular Disease Risk

摘要 大麻的精神活性成分Δ9-四氢大麻酚(Thc)的效力从 在过去十年中，THC对心血管疾病(CVD)风险的影响尚不清楚。 研究表明，THC可能在不利的心血管健康中发挥作用；然而， 大麻中的THC和其他化合物，如大麻二酚(CBD)，对心血管疾病风险的研究还不够深入。 越来越多的证据表明，CBD具有抗炎和抗氧化特性， 有益于心血管系统。这项研究(N=400)的主要目标是检查 根据给药途径对18至30岁大麻吸毒者的血液和尿液THC/CBD进行量化，与 非使用者，关于亚临床心血管疾病风险的客观测量。这项研究将研究THC/CBD对 亚临床心血管风险通过：1)传统心血管风险因素(即腰围、血压、空腹血脂 曲线、血糖和C反应蛋白)；2)血管功能的测量(即，肱动脉血流介导的扩张试验 和动脉顺应性的脉搏波速度测量)。具体目标是：1)检查差异 在测量吸食大麻与不吸食大麻的亚临床心血管疾病风险方面；2)分析 通过大麻给药途径测量亚临床心血管疾病风险；以及3)确定THC/CBD的影响 在大麻组中，血液和尿液水平是衡量亚临床心血管疾病风险的指标。参与者将是 被招募到年龄、性别、种族/民族和收入匹配的小组(n=100) 团队研究中的抽样框架。第一组将是最经常通过钝器(大麻)使用大麻的吸毒者 卷成烟叶)。第二组将是不吸烟草香烟的大麻吸毒者，而且谁最多 经常通过联合使用大麻(大麻卷在没有添加烟草的纸中)。这群人将不会有烟草 曝光。第三组将是吸食大麻的人，他们最经常通过电子设备使用大麻。第四组 将不使用大麻和烟草。测量将在基线和重复的、确认性的 12个月时测量。我们假设，亚临床心血管疾病风险的不同效应通过 给药途径；血液和尿液中较高的THC水平将与 亚临床心血管疾病风险。对50名吸食类似大麻和亚临床大麻的吸毒者进行的试验性研究 心血管疾病风险确定(PI：VIDOT)确认了可行性和知情的研究目的和假设。我们会 利用Vidot博士(流行病学家)的大麻专业知识，与一个多学科专家团队合作： 马丁内斯博士(心脏病专家)、冈萨雷斯博士(物质使用心理学家)、雷迪博士(法医毒物学家)、阿赫特博士 (生物统计学家)、西德尼(心血管顾问)、安东尼(设计顾问)和阿尔沙拉维(机械师) 顾问)来完成总体目标。研究结果将确定与以下物质相关的THC/CBD水平 积极/有害的心血管风险，为心血管疾病风险增加的使用者提供大麻类药物滴定信息。

ABSTRACT The potency of the psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), has increased from 3.7% to 30% over the last decade; yet, the impact of THC on cardiovascular disease (CVD) risk is unclear. Studies suggest that THC may play a role in adverse cardiovascular health; however, the combined levels of THC and other compounds within cannabis, such as cannabidiol (CBD), on CVD risk are understudied. Accumulating evidence suggests that the CBD has anti-inflammatory and antioxidant properties that are beneficial to the cardiovascular system. The overarching goal of this study (N=400) is to examine the impact of blood- and urine-quantified THC/CBD among 18-to-30-year-old cannabis users by route of administration, versus nonusers, on objective measures of subclinical CVD risk. The study will examine the impact of THC/CBD on subclinical CVD risk via: 1) traditional CVD risk factors (i.e., waist circumference, blood pressure, fasting lipid profile, glucose, and CRP); 2) measures of vascular function (i.e., brachial artery flow-mediated dilation testing and pulse wave velocity measurements of arterial compliance). Specific aims are to: 1) Examine the difference in measures of subclinical CVD risk between cannabis users and nonusers; 2) Analyze the difference in measures of subclinical CVD risk by route of cannabis administration; and 3) Determine the impact of THC/CBD blood and urine levels on measures of subclinical CVD risk, within the cannabis groups. Participants will be recruited into an age-, sex-, race/ethnicity-, and income-matched group (n=100 each) from an established sampling frame in the team’s studies. Group 1 will be cannabis users who most often use via blunts (cannabis rolled into a tobacco leaf). Group 2 will be cannabis users who do not smoke tobacco cigarettes and who most often use cannabis via joint (cannabis rolled in paper with no added tobacco). This group will have no tobacco exposure. Group 3 will be cannabis users who most often use cannabis via electronic device (vape). Group 4 will be nonusers of cannabis and tobacco. Measures will be collected at baseline and a repeated, confirmatory measurement at 12-months. We hypothesize that there will be a differential effect of subclinical CVD risk by route of administration; and that higher blood- and urine-quantified THC levels will be positively related to subclinical CVD risk. Pilot studies on a cohort of 50 cannabis users with similar cannabis use and subclinical CVD risk ascertainment (PI: Vidot) confirmed feasibility and informed study aims and hypotheses. We will leverage Dr. Vidot’s (epidemiologist) cannabis expertise in collaboration with a multidisciplinary team of experts: Drs. Martinez (cardiologist), Gonzalez (substance use psychologist), Reidy (forensic toxicologist), Arheart (biostatistician), Sidney (cardiovascular consultant), Anthony (design consultant), and Alshaarawy (mechanistic consultant) to accomplish the overarching goal. Study findings will identify THC/CBD levels associated with positive/deleterious CVD risk to inform cannabinoid titration for users at increased CVD risk.