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

项目摘要 Maritime的使用不仅在增加，而且作为一种“标签外”的附加治疗， 难治性焦虑然而，讽刺的是，虽然数据表明大麻，特别是1999年- 四氢大麻酚（THC），增加焦虑急性，横截面和纵向数据表明，可能的 长期使用大麻与降低焦虑症风险之间的联系。迫切需要进行研究， 了解大麻的影响这些结果。根据大量证据表明大麻具有抗- 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， 焦虑症，我们提出大麻的抗炎特性与其抗焦虑作用有关。 方面的影响.重要的是，先前的工作没有考虑到， 大麻是不同大麻素的复合作用，其药理作用和效果各不相同。 具体来说，大麻二酚（CBD），大麻的一种非拟精神病成分（不会产生“高”）， 被认为具有抗焦虑特性，并可能减轻四氢大麻酚的一些有害影响 （THC）。此外，初步数据，包括我们自己的数据，表明THC和CBD对 焦虑相关的过程，如对炎症标志物和应激反应的影响。关键是， THC和CBD的数量和比例存在巨大差异，商业上可获得并广泛用于各州，如 科罗拉多。因此，CBD与THC的比例可能对抗焦虑和抗抑郁药物具有关键影响。 各种大麻菌株的炎症作用，这反过来可能对1） 对焦虑的影响和2）旨在减少危害的大麻监管政策。 为了解决对大麻素影响的理解上的这一差距，我们建议测试 假设大麻的抗焦虑作用和抗炎特性随着年龄的增长而变化， CBD与THC比率的函数，这些影响可能会揭示混合数据链接 大麻使用和焦虑我们提出了一个独特的观察性研究，采用现实世界的大麻 菌株目前可用于科罗拉多居民，其CBD与THC的比例不同。我们测试了 基于大麻的CBD与THC的不同比率选择大麻的特定菌株[即高CBD菌株 （+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，预计+CBD大麻将减轻焦虑，外周炎症反应 （包括有和没有离体免疫激发的细胞因子水平），以及行为和生物学 在4周的观察过程中对应激诱导的反应。预计拟议的 研究将产生关于哪种大麻品种对焦虑产生最有害影响的信息 和炎症，并告知与大麻使用和监管有关的个人和政策决定。

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.