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: 10619625
• 负责人: Angela Bryan
• 金额: $ 54.53万
• 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/10619625
• 关键词: Acute; Anti-Inflammatory Agents; Attention; Biological; Biological Markers; Biological Process; Blood; Body Weight; Body mass index; Cannabidiol; Cannabinoids; Cannabis; Chronic; Colorado; Complex; Conceptions; Control Groups; Data; Development; District of Columbia; Energy Intake; Epidemiology; Exposure to; Flowers; Goals; Harm Reduction; Health Professional; Individual; Inflammation; Inflammatory; Insulin Resistance; Interleukin-6; Intoxication; Legal; Marijuana; Marketing; Matched Group; Measures; Mediating; Medical; Metabolic; Metabolic Diseases; Metabolism; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Peripheral; Policies; Prevalence; Process; Property; Public Health; Recreation; Research; Research Design; Risk; TNF gene; Testing; Tetrahydrocannabinol; Translating; Variant; Weight; cytokine; design; diabetogenic; drug discovery; experience; indexing; inflammatory marker; insulin sensitivity; marijuana decriminalization; marijuana legalization; marijuana use; marijuana user; response; waist circumference

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.

项目概要 随着美国各州将大麻非刑事化和合法化，大麻的使用正在增加。鉴于流行的观念和 一些经验证据表明，大麻使用者在急性中毒期间会经历热量摄入增加， 有人担心较高的娱乐性大麻使用率可能会加剧当前的公共卫生状况 肥胖危机和相关代谢疾病；主要是2型糖尿病。然而矛盾的是，交叉 截面数据表明长期吸食大麻与较低体重指数 (BMI) 之间存在关联， 尽管有数据支持更高的热量，但肥胖、胰岛素抵抗和 2 型糖尿病的患病率仍然很高 急剧摄入。我们实验室的初步数据表明，大麻品系中存在不同的大麻素 （例如 Δ9-四氢大麻酚 (THC) 和大麻二酚 (CBD)）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 型糖尿病相关，例如胰岛素抵抗。关键的是，有巨大的 市售的 THC 和 CBD 的数量和比例存在多样性，并在以下州广泛使用 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 这可能是由于现在使用的大麻的效力或组成成分造成的，可能与以下方面有关 胰岛素敏感性的变异性是 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 不同体重范围的大麻使用者。我们的总体假设是，炎症效应 大麻的使用随 CBD 与 THC 的比例而变化，炎症可能是通过 大麻会影响胰岛素敏感性，从而影响 2 型糖尿病的风险。数据来自于此 严格设计的研究可能会揭示大麻使用/代谢疾病悖论。目标是 测试三种现实世界商业大麻品种的效果，它们的比例明显不同 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。我们采用两种观察设计： 戒烟至少三个月的不频繁使用者的急性影响以及更多研究 使用三种大麻花品种之一四个星期对大麻使用者产生持续影响 与不使用大麻的匹配对照组进行比较。将测量 THC 和 CBD 的血液水平 两种情况的暴露期之前、期间和之后，以及血液中 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的 向公众和卫生专业人员及时提供有关大麻使用影响的数据，包括 各种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 为个人和政策层面的决定提供信息，以减少大麻使用的危害。