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

项目摘要 随着美国各州大麻合法化和合法化，大麻的使用量正在上升。考虑到流行的概念和 一些经验证据表明，大麻使用者在急性中毒期间卡路里摄入量增加， 有人担心，娱乐性大麻使用率的提高可能会加剧当前的公共健康 肥胖危机和相关的代谢性疾病；主要是2型糖尿病。然而，矛盾的是，克罗斯 部分数据表明，长期吸食大麻与较低的体重指数(BMI)之间存在关联， 肥胖、胰岛素抵抗和2型糖尿病的患病率，尽管数据支持更高的卡路里 敏锐地摄取。我们实验室的初步数据表明，大麻菌株中存在不同的大麻类化合物 (例如，∆，9-四氢大麻酚和大麻二酚)对过程产生不同的生物效应 通过对炎症标志物的影响与2型糖尿病如胰岛素抵抗有关。关键的是，有巨大的 THC和CBD的数量和比例的多样性可在商业上获得并在以下国家广泛使用 科罗拉多州及其对肥胖过程的影响尚不清楚。潜在炎症状态的变化 这可能是由于大麻的效力或成分造成的，因为它现在的使用很可能与 胰岛素敏感性的变异性，这是2型糖尿病的关键生物标记物。 我们建议仔细研究大麻素对炎性细胞因子和胰岛素敏感性的影响。 在不同体重范围的大麻使用者中。我们的全球假说是 大麻的使用随着CBD/THC比率的变化而变化，炎症可能是通过 哪种大麻会影响胰岛素敏感性，从而影响患2型糖尿病的风险。来自于此的数据 严格设计的研究可能会揭示大麻使用/代谢性疾病的悖论。我们的目标是 为了测试三种在比例上有明显差异的真实可获得的大麻品种的效果 从CBD到THC。为此，我们将测试三种不同大麻产品的效果：CBD产品 (14%CBD，0%THC)、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性设计：一项研究 戒酒至少三个月的不频繁吸食者的急性影响，以及一项关于更长时间的研究 被分配使用三种大麻花品种之一四周的大麻吸毒者的持续影响 与不使用大麻的匹配控制组进行比较。将测量血液中THC和CBD的水平 在这两种情况下，暴露前、暴露期间和暴露后，血液中THC和CBD之间的关系 炎症和胰岛素敏感性都将被测量。这些研究的结果将提供关键的 及时向公众和卫生专业人员提供关于大麻使用影响的数据，包括 不同菌株对糖尿病发生过程的不同影响。这些数据是急需的，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. ∆9-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.