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: 10190874
• 负责人: L. Cinnamon Bidwell
• 金额: $ 56.26万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10190874
• 关键词: Acute; Address; Anti-Anxiety Agents; Anti-Inflammatory Agents; Antiinflammatory Effect; Anxiety; Anxiety Disorders; Behavioral; Biological; Biological Markers; Blood; Cannabidiol; Cannabinoids; Chronic; Colorado; Control Groups; Data; Disease; Equipment and supply inventories; Etiology; Exposure to; 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.

项目摘要 大麻的使用不仅在增加，而且吸引了作为“标签”附加疗法的吸引力 防治焦虑。但是，矛盾的是，尽管数据表明大麻，特别是Δ9- 四氢大麻酚（THC）急性增加焦虑，横截面和纵向数据表明可能 慢性大麻使用与焦虑症的风险较低之间的联系。需要研究至关重要 了解大麻的影响。考虑到大麻有抗的考虑证据 炎症特性以及进一步的证据表明炎症在病因中起关键作用 焦虑症，我们建议大麻的抗炎特性与其抗焦虑作用有关 效果。重要的是，先前的工作并未考虑到精神和抗炎作用 大麻是不同大麻素的复合作用，它们的药理学和作用各不相同。 特别是大麻的大麻成分（不产生“高”）是大麻二醇（CBD），是 被认为具有抗焦虑特性，并可能减轻四氢大麻酚的某些有害作用 （THC）。此外，包括我们自己在内的初步数据表明，THC和CBD对 与焦虑相关的过程，例如对炎症标记的影响和压力反应。至关重要的是 THC和CBD的商业可用数量和比例巨大，并在诸如此类的州广泛使用 科罗拉多州。因此，CBD与THC的比率可能对抗焦虑和抗 - 各种大麻菌株的炎症作用又可能对1具有重要意义 对焦虑和2）旨在减少伤害的大麻调节政策。 为了解决这一差距在理解大麻素的影响方面，我们建议测试 大麻的抗焦虑作用和抗炎特性的假设随着 CBD与THC的比率的功能，并且这些效果可能会揭示混合数据链接 大麻使用和动画。我们提出了一项独特的观察性研究，该研究采用现实世界大麻 目前可为科罗拉多州居民使用的菌株，其CBD与THC比率不同。我们测试了 根据其分化CBD与THC比的分化选择的特定菌株[即高CBD菌株 （+CBD/-THC），A 1：1（+THC/+CBD）菌株和典型的基于THC的应变+THC/-CBD）] 炎症，期望 +CBD大麻会减轻焦虑，周围炎症反应 （包括有或没有前体免疫挑战的细胞因子水平）以及行为和生物学 在观察4周的过程中，对压力诱导的反应。预计提议 研究将产生有关哪些大麻菌株对焦虑产生最有害影响的信息 以及炎症，并为与大麻使用和法规有关的个人和政策决定提供信息。

项目成果

Cannabis use and sleep: Expectations, outcomes, and the role of age.

• DOI: 10.1016/j.addbeh.2020.106642
• 发表时间: 2021-01
• 期刊: Addictive behaviors
• 影响因子: 4.4
• 作者: Winiger EA;Hitchcock LN;Bryan AD;Cinnamon Bidwell L
• 通讯作者: Cinnamon Bidwell L

THC in breath aerosols collected with an impaction filter device before and after legal-market product inhalation-a pilot study.

• DOI: 10.1088/1752-7163/acd410
• 发表时间: 2023-05-22
• 期刊: Journal of breath research
• 影响因子: 3.8

Using Population Pharmacokinetic Modeling to Estimate Exposure to Δ9-Tetrahydrocannabinol in an Observational Study of Cannabis Smokers in Colorado.

• DOI: 10.1097/ftd.0000000000000882
• 发表时间: 2021-08-01
• 期刊: Therapeutic drug monitoring
• 影响因子: 2.5
• 作者: Sempio C;Bidwell LC;Hutchison K;Huestis MA;Klawitter J;Christians U;Henthorn TK
• 通讯作者: Henthorn TK

Process evaluation for the adaptation, testing and dissemination of a mobile health platform to support people with HIV and tuberculosis in Irkutsk, Siberia.

• DOI: 10.1136/bmjopen-2021-054867
• 发表时间: 2022-03-29
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Hodges J;Waldman AL;Koshkina O;Suzdalnitsky A;Schwendinger J;Vitko S;Plenskey A;Plotnikova Y;Moiseeva E;Koshcheyev M;Sebekin S;Zhdanova S;Ogarkov O;Heysell S;Dillingham R
• 通讯作者: Dillingham R