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2000年开始增加， 在过去的十年中，THC的发病率为3.7%至30%;然而，THC对心血管疾病（CVD）风险的影响尚不清楚。 研究表明，THC可能在不良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CVD风险的研究不足。 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。本研究（N=400）的总体目标是检查以下因素的影响： 血液和尿液定量THC/CBD在18至30岁的大麻使用者中按给药途径， 非使用者，对亚临床CVD风险的客观测量。该研究将探讨货柜码头处理费/生物多样性公约对 亚临床CVD风险通过：1）传统CVD风险因素（即，腰围，血压，空腹血脂 曲线、葡萄糖和CRP）; 2）血管功能的测量（即，肱动脉血流介导舒张试验 和动脉顺应性的脉搏波速度测量）。具体目标是：（1）检查差异 在大麻使用者和非使用者之间的亚临床CVD风险的措施; 2）分析差异， 通过大麻施用途径测量亚临床CVD风险;以及3）确定THC/CBD的影响 血液和尿液水平对亚临床心血管疾病风险的措施，在大麻组。参与者将被 招募到一个年龄，性别，种族/民族，和收入匹配的组（n=100），从一个既定的 在团队的研究中，第一组是大麻使用者，他们最常通过钝头器（大麻 卷成烟叶）。第二组将是不吸烟草香烟的大麻使用者，他们大多数 经常通过接头吸食大麻（大麻卷在纸里，不加烟草）。这一组将没有烟草 exposure.第三组是最常通过电子设备（vape）使用大麻的大麻使用者。第4组 将是大麻和烟草的非使用者。将在基线时收集测量值，并进行重复的确证性研究。 12个月的测量。我们假设亚临床心血管疾病风险的差异效应是 给药途径;以及较高的血液和尿液定量THC水平将与 亚临床CVD风险。对50名具有类似大麻使用和亚临床症状的大麻使用者进行的试点研究 CVD风险确定（PI：Vidot）证实了可行性，并告知了研究目的和假设。我们将 利用Vidot博士（流行病学家）与多学科专家团队合作的大麻专业知识： Drs. Martinez（心脏病专家）、Gonzalez（药物使用心理学家）、Reidy（法医毒理学家）、Arheart （生物统计学家）、Sidney（心血管顾问）、Anthony（设计顾问）和Alshaarawy（机械 （一）实现总体目标。研究结果将确定THC/CBD水平与 积极/有害的CVD风险，为CVD风险增加的用户提供大麻素滴定信息。

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.