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

探索大麻的抗炎特性及其与胰岛素敏感性的相关性

• 批准号: 10400315
• 负责人: Angela Bryan
• 金额: $ 1.63万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400315
• 关键词: Acute; Anti-Inflammatory Agents; Biological; Biological Markers; Biological Process; Blood; Body mass index; Cannabidiol; Cannabinoids; Cannabis; Chronic; Colorado; Complex; Conceptions; Control Groups; Data; Energy Intake; Flowers; Goals; Health Professional; Individual; Inflammation; Inflammatory; Insulin Resistance; Intoxication; Light; Marijuana; Measures; Medical; Metabolic Diseases; Metabolism; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Policies; Prevalence; Process; Property; Public Health; Research; Research Design; Risk; Testing; Tetrahydrocannabinol; Time; Variant; Weight; cytokine; design; diabetogenic; drug discovery; experience; inflammatory marker; insulin sensitivity; marijuana decriminalization; marijuana legalization; marijuana use; marijuana user

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.

项目摘要 随着美国国家将大麻合法化和合法化，其使用正在上升。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的热量摄入量增加， 人们担心较高的休闲大麻使用率可能加剧当前的公共卫生 肥胖和相关代谢疾病的危机；主要是2型糖尿病。然而，矛盾的是交叉 截面数据显示了慢性大麻使用与下体重指数（BMI）之间的关联， 肥胖症的患病率，胰岛素抵抗和2型糖尿病的发生率，支持更高热量的目的地数据 敏锐的摄入量。我们实验室的初步数据表明，大麻菌株中存在的不同大麻素 （例如∆9-四氢大麻酚（THC）和大麻二酚（CBD））对过程产生差异性生物学影响 与2型糖尿病相关，例如通过对炎症标志物的影响进行胰岛素抵抗。至关重要的是，有巨大 THC和CBD市售的数量和比率的多样性和比例在诸如此类的州广泛使用 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构成组成部分而造成的，因为它现在可能与 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 在整个体重谱系中的大麻使用者中。我们的全球假设是 大麻使用的变化是CBD与THC的比率的函数，该注射可能是一条途径 大麻会影响胰岛素敏感性，从而影响2型糖尿病的风险。来自此的数据 严格设计的研究可能会阐明大麻使用/代谢疾病悖论。目标是 测试三种现实世界上商业上可用的大麻菌株的影响，它们的比例明显不同 CBD到THC的。为此，我们将测试三种不同大麻产品的影响：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设计：一项研究 至少三个月避免的少数用户的急性影响，并进行了更多研究 在分配到三个大麻花菌株之一的大麻使用者中的持续效果 与不使用大麻的匹配的对照组相比。将测量THC和CBD的血液水平 两种情况下暴露期间，期间和之后，血液中THC和CBD之间的关联 并且将测量炎症和胰岛素敏感性。这些研究的结果将提供关键 并及时向公众和卫生专业人员进行有关大麻使用影响的数据，包括 各种菌株对糖尿病生成过程的差异作用。迫切需要这些数据才能 告知个人和政策级别的决策，以减少大麻使用的危害。