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

酒精使用障碍和焦虑的共同机制以及内源性大麻素系统的影响

• 批准号: 10443624
• 负责人: Renee Martin-Willett
• 金额: $ 4.16万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10443624
• 关键词: Alcohol consumption; Alcohol-Related Disorders; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anxiety; Anxiety Disorders; Behavior; Biological Markers; Brain; Cannabidiol; Cannabinoids; Characteristics; Cognition; Development; Discrimination; Disease; Distant; Dose; Effectiveness; Emotional; Evidence based treatment; Exposure to; Extinction (Psychology); Face; Fright; Goals; Health Services Accessibility; Heart Rate; Individual; Inflammation; Inflammatory; Memory; Minority Health Research; Modeling; Neurobiology; Outcome; Participant; Patients; Peripheral Nervous System; Pharmaceutical Preparations; Physiological; Population; Predisposition; Process; Property; Psychopathology; Psychopharmacology; Receptor Signaling; Reporting; Research; Research Personnel; Rewards; Risk; Sampling; Severities; Sex Discrimination; Sexual and Gender Minorities; Stress; Substance Use Disorder; Symptoms; System; Testing; Tetrahydrocannabinol; Time; Training; Underrepresented Populations; alcohol response; alcohol use disorder; anxiety symptoms; anxiety-related disorders; cannabinoid receptor; comorbidity; diagnostic tool; endocannabinoid signaling; endogenous cannabinoid system; endophenotype; ethnic minority; exogenous cannabinoid; experience; gender minority; learning extinction; marijuana use; microbiome; neurobiological mechanism; new therapeutic target; novel; psychologic; racial minority; racial minority population; reduce symptoms; sexual minority; social stigma; societal costs; stress related disorder; therapeutic target

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.

项目摘要 焦虑症和酒精相关障碍（ARD）都是生理炎症性的， 使个人和社会付出高昂代价的心理衰弱疾病。此外，酒精的存在 使用相关障碍（ARD）可以使患焦虑相关障碍的几率加倍。当前治疗 焦虑症或ARDs的选择可能有效缓解一种疾病的症状，但可能 另一种会加重症状现有的治疗通常不针对他们共同的神经生物学 机制，反过来又强调缺乏系统和神经生物学变化的客观标志物 与这两种疾病相关，并限制了单焦点诊断工具和治疗方法的有效性。 目标的此外，对于患有ARDs或焦虑症的性少数和少数民族来说， 疾病，包括耻辱感增加，获得护理的问题，以及遭受歧视，所有这些 都没有得到充分的研究需要新的治疗靶点，以便更公平地研究 不同的群体，解释了焦虑症的生理效应和与ARDs的共病。 内源性大麻素系统（ECS）及其与炎症反应的关系可能是一个潜在的靶点。 流程.令人鼓舞的是，外源性大麻素如大麻二酚（CBD）已被证明是差异性的。 作用于ECS的炎症机制，CBD单独或与THC一起也可以剂量依赖性地 降低对酒精的奖励反应，具有抗焦虑特性，有助于消退学习， 可能刺激神经类固醇生成，这被认为是支持恐惧消退和限制过度觉醒。 因此，本研究将探讨外源性大麻素对焦虑症状的影响。 参与者的饮酒量，主观焦虑症状和共同的生物标志物汇总风险 焦虑和ARDs评分。此外，鉴于目前性别和族裔代表性不足， 少数民族在焦虑和ARDs的研究，这项研究将重点放在这些人群，以及调查 歧视相关压力对相同结果的影响。该提案的长期目标是 扩展申请人在代表性不足的群体中进行包容性研究的背景 同时在神经生物学和精神药理学方面建立专业知识， 药物使用障碍。最终开发出一种综合的、以证据为基础的治疗模式， 包括公平和多样化的样本，并广泛适用于患者是一个遥远的，但完全 这是该项目支持的目标。