Novel approaches to understanding the role of cannabinoids and inflammation in anxiety

了解大麻素和炎症在焦虑中的作用的新方法

• 批准号: 9283876
• 负责人: L. Cinnamon Bidwell
• 金额: $ 56.43万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9283876
• 关键词: Acute; Address; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anti-inflammatory; Anxiety; Anxiety Disorders; Behavioral; Biological; Biological Markers; Blood; Cannabidiol; Cannabinoids; Chronic; Colorado; Control Groups; Data; Disease; Equipment and supply inventories; Etiology; Goals; Harm Reduction; Immune; Individual; Inflammation; Inflammatory; Inflammatory Response; Label; Laboratories; Light; Link; Marijuana; Matched Group; Measures; Mediating; Medical; Modeling; Observational Study; Outcome; Patient Self-Report; Peripheral; Pharmacology; Physiological; Play; Policies; Process; Property; Public Health; Regulation; Research; Resistance; Risk; Role; Stress; Testing; Tetrahydrocannabinol; Time; Traction; Work; acute stress; anxious; base; biological adaptation to stress; clinically relevant; cytokine; design; inflammatory marker; marijuana use; marijuana user; novel strategies; response; stress reactivity; stress related disorder; stressor

Project Summary Marijuana use is not only increasing, but gaining traction for use as an “off-label” add-on therapy for treatment-resistant anxiety. Paradoxically, however, while data suggest that marijuana, in particular ∆9- tetrahydrocannabinol (THC), increases anxiety acutely, cross sectional and longitudinal data suggest possible links between chronic marijuana use and lower risk for anxiety disorders. Research is critically needed to understand the effects of marijuana these outcomes. In light of considerable evidence that marijuana has anti- inflammatory properties and, further evidence suggesting that inflammation plays a pivotal role in the etiology of anxiety disorders, we propose that the anti-inflammatory properties of marijuana are linked with its anxiolytic effects. Importantly, prior work has not considered that the psychotropic and anti-inflammatory effects of marijuana are the compound action of different cannabinoids, which vary in their pharmacology and effects. Specifically, cannabidiol (CBD), a non-psychotomimetic component of marijuana (doesn’t produce a “high”), is thought to have anxiolytic properties and may mitigate some of the harmful effects of tetrahydrocannabinol (THC). Further, preliminary data, including our own, suggest that THC and CBD render differential effects on anxiety-related processes, such as effects on inflammatory markers and stress response. Critically, there is huge diversity in the amounts and ratio of THC and CBD commercially available and widely used in states like Colorado. Therefore, the ratio of CBD to THC may have a pivotal impact on the anxiolytic and anti- inflammatory effects of various strains of marijuana, which in turn may have important implications for 1) effects on anxiety and 2) marijuana regulation policies aimed at harm reduction. In order to address this gap in understanding of the effects of cannabinoids, we propose to test the hypothesis that the anxiolytic effects and anti-inflammatory properties of marijuana vary as a function of the ratio of CBD to THC, and that these effects may shed light on the mixed data linking cannabis use and anxiety. We propose a unique observational study that employs real-world marijuana strains currently available to Colorado residents that vary in their CBD to THC ratios. We test the effects of specific strains of marijuana selected based on their differing CBD to THC ratios [i.e. a high CBD strain (+CBD/-THC), a 1:1 (+THC/+CBD) strain, and a typical THC-based strain +THC/-CBD)] on anxiety and inflammation, expecting that +CBD marijuana will mitigate anxiety, peripheral inflammatory responses (including cytokine levels with and without an ex-vivo immune challenge), and behavioral and biological responses to stress induction over the course of 4 weeks of observation. It is expected that the proposed research will generate information about which marijuana strains produce the most harmful effects on anxiety and inflammation and inform personal and policy decisions related to marijuana use and regulation.

项目概要 大麻的使用不仅在增加，而且作为一种“标签外”附加疗法也越来越受欢迎 然而，矛盾的是，虽然数据表明大麻，尤其是 Δ9- 四氢大麻酚 (THC) 会急剧增加焦虑，横截面和纵向数据表明可能 长期使用大麻与降低焦虑症风险之间的联系至关重要。 鉴于大量证据表明大麻具有抗药性，了解大麻对这些结果的影响。 炎症特性，进一步的证据表明炎症在病因学中起着关键作用 对于焦虑症，我们认为大麻的抗炎特性与其抗焦虑作用有关 重要的是，先前的工作并未考虑到精神作用和抗炎作用。 大麻是不同大麻素的复合作用，其药理和作用各不相同。 具体来说，大麻二酚 (CBD) 是大麻的一种非拟精神病成分（不会产生“快感”）， 被认为具有抗焦虑特性，可以减轻四氢大麻酚的一些有害影响 此外，包括我们自己在内的初步数据表明，THC 和 CBD 对人体产生不同的影响。 与焦虑相关的过程，例如对炎症标志物和应激反应的影响，至关重要。 商业上可买到并广泛使用的 THC 和 CBD 的数量和比例存在巨大差异 因此，CBD与THC的比例可能对抗焦虑和抗焦虑产生关键影响。 各种大麻品种的炎症作用，这反过来可能对以下方面产生重要影响：1) 对焦虑的影响；2）旨在减少危害的大麻监管政策。 为了弥补对大麻素影响的理解上的差距，我们建议测试 大麻的抗焦虑作用和抗炎特性随不同因素而变化的假设 CBD 与 THC 比例的函数，这些影响可能有助于揭示混合数据链接 我们提出了一项采用现实世界大麻的独特观察研究。 目前科罗拉多州居民可以使用的菌株，其 CBD 与 THC 的比例不同，我们测试了其效果。 根据不同的 CBD 与 THC 比例选择特定的大麻品种 [即高 CBD 品种] (+CBD/-THC)、1:1 (+THC/+CBD) 菌株和典型的基于 THC 的菌株 +THC/-CBD)] 对焦虑和 炎症，期望 +CBD 大麻能减轻焦虑、外周炎症反应 （包括有或没有离体免疫挑战的细胞因子水平），以及行为和生物学 预计在 4 周的观察过程中对压力诱导的反应。 研究将产生有关哪些大麻品种对焦虑产生最有害影响的信息 和炎症，并为与大麻使用和监管相关的个人和政策决策提供信息。