Shared mechanisms of alcohol use disorder and Anxiety and effects of the endocannabinoid system

项目摘要 焦虑症和酒精相关障碍(ARD)都是生理性炎症性和 精神衰弱的疾病，具有高昂的个人和社会成本。此外，酒精的存在 使用相关障碍(ARD)会使患焦虑相关障碍的几率增加一倍。目前的治疗方法 焦虑症或ARDS的选择可能在缓解一种障碍的症状方面有效，但也可能 加重了另一个人的症状。现有的治疗方法通常不针对他们共同的神经生物学 机制，进而突显缺乏系统和神经生物学变化的客观标记物 与这两种情况相关，并限制了单一诊断工具和治疗的有效性 目标。此外，患有ARDS或焦虑症的性少数群体和少数民族还面临着额外的挑战。 疾病，包括耻辱增加、获得护理的问题和遭受歧视，所有这些 被严重忽视了。需要更公平地研究新的治疗靶点。 不同的群体，既有焦虑症状的生理影响，也有ARDS的共病。 一个这样的潜在靶点可能是内源性大麻素系统(ECS)及其与炎症的关系 流程。令人振奋的是，外源性大麻素，如大麻二酚(CBD)已被证明具有不同的 作用于ECS的炎症机制，CBD单独或与THC一起也可能呈剂量依赖关系 降低对酒精的奖赏反应，具有缓解焦虑的特性，有助于消亡学习，以及 可能会刺激神经类固醇的生成，这被认为支持恐惧消退和限制过度唤醒。 因此，本研究将探讨外源性大麻素对焦虑症患者的影响。 参与者关于饮酒、主观焦虑症状和共同生物标记物汇总风险的研究 焦虑和不良反应评分。此外，鉴于目前性和族裔代表性不足， 在少数民族对焦虑和不良反应的研究中，本研究将重点放在这些人群以及调查 与歧视相关的压力对相同结果的影响。这项提议的长期目标是 在代表性不足的群体中进行包容性研究时，扩大申请者的背景 在培养神经生物学和精神药理学方面的专业知识的同时 物质使用障碍。最终开发一种综合的循证治疗模式，即 包含公平和多样化的样本并广泛适用于患者是一个遥远而又完整的问题 这个项目支持的有价值的目标。

Project Summary Anxiety disorders and alcohol related disorders (ARD) are both physiologically inflammatory and psychologically debilitating illnesses with high individual and societal costs. In addition, the presence of alcohol use related disorder (ARD) can double the odds of having an anxiety-related disorder. Current treatment options for anxiety disorders or ARDs may be effective in alleviating symptoms for one disorder, but may exacerbate symptoms for the other. Available treatments generally do not target their shared neurobiological mechanisms, in turn highlighting the lack of an objective marker of systemic and neurobiological change associated with both conditions, and limiting the effectiveness of unifocal diagnostic tools and therapeutic targets. Furthermore, there are additional challenges for sexual and ethnic minorities with ARDs or anxiety disorders, including increased stigma, problems accessing care, and exposure to discrimination, all of which are sorely understudied. There is a need for new therapeutic targets that are studied more equitably across diverse groups that account for both physiological effects of anxiety symptomology and comorbidity with ARDs. One such potential target may be the endocannabinoid system (ECS) and its relationship with inflammatory processes. Promisingly, exogenous cannabinoids such as cannabidiol (CBD) have been shown to differentially act on inflammatory mechanisms of the ECS, and CBD alone or with THC may also dose-dependently decrease reward response to alcohol, have anxiolytic properties, be assistive to extinction learning, and possibly stimulate neurosteroidogenesis, which is thought to support fear extinction and limit hyperarousal. Thus, this study will investigate the effects of exogenous cannabinoids among anxiety-symptomatic participants on alcohol consumption, subjective anxiety symptoms, and a shared biomarker summary risk score for anxiety and ARDs. Furthermore, given the current underrepresentation of sexual and ethnic minorities in research on anxiety and ARDs, this study will focus on these populations as well as investigate the effects of discrimination-related stress on the same outcomes. The long-term goal of this proposal is to expand upon the applicant’s background in conducting inclusive research among underrepresented groups while building expertise in the neurobiology and psychopharmacology of co-occurring psychological and substance use disorders. The eventual development of an integrated, evidence-based treatment model that is inclusive of equitable and diverse samples and is broadly applicable across patients is a distant, yet wholly worthwhile goal which this project supports.