Exploring the anti-inflammatory properties of cannabis and their relevance to insulin sensitivity

项目摘要 随着美国各州将大麻合法化和合法化，大麻的使用正在增加。鉴于流行的概念和 一些经验证据表明，大麻使用者在急性中毒期间热量摄入增加， 人们担心，娱乐性大麻使用率的提高可能会加剧目前的公共健康状况， 肥胖和相关代谢疾病的危机;主要是2型糖尿病。然而，令人遗憾的是， 部分数据表明长期使用大麻与较低的身体质量指数（BMI）之间的关联， 肥胖、胰岛素抵抗和2型糖尿病的患病率，尽管数据支持较高的热量 摄入量急剧增加。我们实验室的初步数据表明，大麻品种中存在不同的大麻素， (e.g.Δ9-四氢大麻酚（THC）和大麻二酚（CBD））对过程产生不同的生物学效应 与2型糖尿病相关，如胰岛素抵抗，通过对炎症标志物的影响。关键是， THC和CBD的数量和比例的多样性商业上可获得并广泛用于各州，如 科罗拉多及其对肥胖过程的影响尚不清楚。潜在炎症状态的变化 目前使用的大麻的效力或组成成分可能造成的损害， 胰岛素敏感性的变异性，2型糖尿病的关键生物标志物。 我们建议仔细研究大麻素对炎症细胞因子和胰岛素敏感性的影响 大麻使用者的体重变化我们的总体假设是， 大麻的使用随着CBD与THC的比例而变化，炎症可能是一种途径， 大麻会影响胰岛素敏感性，从而增加患2型糖尿病的风险。数据从该 严格设计的研究可能揭示大麻使用/代谢疾病的悖论。目标是 测试三种真实的世界上可商购的大麻品种的效果， 从CBD到THC为此，我们将测试三种不同大麻产品的效果：一种CBD产品 (14 THC产品（14%THC，0%CBD）和THC+CBD产品（7%THC，7%CBD）。 急性和慢性炎症和胰岛素敏感性。我们采用了两种观察设计：一项研究 一项研究表明，对戒烟至少三个月的非频繁使用者的急性影响， 在被分配使用三种大麻花品种之一四周的大麻使用者中的持续影响 与不使用大麻的对照组进行比较。将测量THC和CBD的血液水平 在这两种情况下，暴露期之前，期间和之后，以及血液中THC和CBD之间的关联 并测量炎症和胰岛素敏感性。这些研究的结果将提供关键的 向公众和卫生专业人员及时提供关于大麻使用影响的数据， 不同菌株对糖尿病发生过程的不同影响。迫切需要这些数据，以便 为个人和政策一级的决定提供信息，以减少大麻使用的危害。

Project Summary As U.S. states decriminalize and legalize cannabis, its use is on the rise. Given the popular conception and some empirical evidence that cannabis users experience increased caloric intake during acute intoxication, there are concerns that higher rates of recreational marijuana use could exacerbate the current public health crisis of obesity and associated metabolic disease; chiefly type 2 diabetes. Paradoxically, however, cross sectional data demonstrate associations between chronic marijuana use and lower body mass index (BMI), prevalence of obesity, insulin resistance, and rates of type 2 diabetes, despite data supporting higher caloric intake acutely. Preliminary data from our lab suggest that different cannabinoids present in marijuana strains (e.g. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)) render differential biologic effects on processes relevant to type 2 diabetes like insulin resistance via effects on inflammatory markers. Critically, there is huge diversity in the amounts and ratio of THC and CBD commercially available and widely used in states like Colorado and their impact on obesity processes is not known. Variations in the underlying inflammatory state that may result from the potency or constituent components of cannabis as it is now used likely relate to variability in insulin sensitivity, a critical biomarker of type 2 diabetes. We propose to carefully study the effects of cannabinoids on inflammatory cytokines and insulin sensitivity in cannabis users across the weight spectrum. Our global hypothesis is that the inflammatory effects of cannabis use vary as a function of the ratio of CBD to THC, and that inflammation may be a pathway by which cannabis influences insulin sensitivity and, thus, risk for type 2 diabetes. Data from this rigorously designed study may shed light on the cannabis use/metabolic disease paradox. The goal is to test the effects of three real world commercially-available cannabis strains that differ markedly in their ratio of CBD to THC. To that end, we will test the effects of three different cannabis products: a CBD product (14% CBD, 0% THC), a THC product (14% THC, 0% CBD), and a THC+CBD product (7% THC, 7% CBD) on inflammation and insulin sensitivity both acutely and chronically. We employ two observational designs: a study of acute effects with infrequent users who have been abstinent at least three months and a study of more sustained effects in cannabis users assigned to four weeks of use of one of three cannabis flower strains versus a matched control group who do not use cannabis. Blood levels of THC and CBD will be measured before, during, and after the exposure period in both cases, and associations between THC and CBD in blood and both inflammation and insulin sensitivity will be measured. Results from these studies will provide critical and timely data to the public and health professionals regarding the effects of cannabis use, including differential effects of various strains, on diabetogenic processes. These data are urgently needed in order to inform individual and policy level decisions in order to reduce the harm of cannabis use.