Evaluating Contributors to Relapse in Comorbid Major Depressive Disorder and Cannabis Use Disorder

评估共病重度抑郁症和大麻使用障碍复发的因素

• 批准号: 10533526
• 负责人: Erin Lindsey Martin
• 金额: $ 4.68万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10533526
• 关键词: 2-arachidonylglycerol; Acute; Address; Adult; Age; Attenuated; Behavior; Biological; Biological Markers; Blood; Blood specimen; Brain; Cannabis; Clinical; Clinical Trials; Communication; Desire for food; Development; Eating; Endocannabinoids; Enzymes; Funding; Future; Heart Rate; Hydrocortisone; Incidence; Individual; Intervention; Laboratories; Ligands; Major Depressive Disorder; Mentors; Mentorship; Moods; Outcome; Participant; Pattern; Peripheral; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Public Health; Relapse; Reporting; Research; Research Design; Risk; Severities; Sleep; Sleep Disorders; Statistical Data Interpretation; Stress; Stress Tests; Symptoms; Time; Training; Translational Research; Treatment outcome; Trier Social Stress Test; United States Food and Drug Administration; Visit; Withdrawal; Withdrawal Symptom; Woman; acute stress; addiction; affective disturbance; anandamide; biological adaptation to stress; cannabis withdrawal; comorbidity; craving; drug craving; endocannabinoid signaling; endogenous cannabinoid system; experience; insight; marijuana use; marijuana use disorder; men; negative affect; novel; novel therapeutics; prevent; programs; psychiatric comorbidity; receptor; recruit; relapse risk; response; screening; social stress; social stressor

Nearly one-fifth of individuals that have used cannabis in the past year have Cannabis Use Disorder (CUD), and nearly one-third of individuals with CUD have comorbid Major Depressive Disorder (MDD). Comorbid MDD/CUD is associated with greater rates of addiction treatment-seeking and worse treatment outcomes relative to CUD alone. However, there is no available pharmacotherapy for CUD and the few clinical trials targeting comorbid MDD/CUD have been unsuccessful. One potential explanation for worsened clinical outcomes in comorbid MDD/CUD is that two major contributors to relapse in CUD, cannabis withdrawal symptoms and stress, may be enhanced by the addition of MDD. This is hypothesized due to the overlap across cannabis withdrawal and MDD symptoms and the enhanced stress response observed in people with MDD alone relative to neurotypical individuals. Both cannabis withdrawal and stress response are regulated by the endocannabinoid (eCB) system; evidence of this has been observed both centrally (in brain) and peripherally (in blood). Because the eCB system has been associated with these major contributors to relapse, it presents a potential target for the development of addiction pharmacotherapy. Furthermore, eCB dysregulation observed in people with MDD compared to neurotypical individuals suggests eCB modulation may have additional utility in people with comorbid MDD/CUD relative to CUD alone. However, it is currently unknown if the eCB system is uniquely dysregulated in comorbid MDD/CUD relative to CUD alone (Aim 1), if cannabis withdrawal severity is enhanced in comorbid MDD/CUD relative to CUD alone (Aim 2), or if comorbid MDD/CUD is associated with enhanced stress responding relative to CUD alone (Aim 3). To address these aims, thirty adults (15 CUD, 15 MDD/CUD) will be recruited to complete four in-person laboratory visits over one week. The first visit will be completed during cannabis use-as-usual and the remaining three visits will occur during acute withdrawal. Blood samples will be collected at three time points during each visit to assess eCB tone and participants will complete cannabis withdrawal symptom assessments at multiple time points over the week. On the final day of study participation, participants will be subjected to a social stress test. Subjective experiences of stress and drug craving, objective biomarkers of stress such as blood cortisol and heart rate, and blood eCBs will be collected prior to stress exposure and at four time points thereafter. Outcomes from the proposed project will be used to determine the relevance of eCB modulation as a pharmacotherapeutic strategy for comorbid MDD/CUD in the context of future clinical trial development. Over the course of the proposed project, the applicant (Erin Martin) will receive mentorship in key aspects of translational research including study design and implementation, scientific communication, and advanced statistical analysis. This training will be applied to the development of a future independent research program examining addiction in people with psychiatric comorbidities.

在过去一年中使用大麻的人中，将近五分之一的人患有大麻使用障碍（CUD）， 近三分之一的患有CUD的人患有重大抑郁症（MDD）。合并 MDD/CUD与较高的成瘾治疗率和较差的治疗结果有关 相对于单独的cud。但是，没有可用的CUD药物和少数临床试验的药物治疗 靶向合并的MDD/CUD并未成功。临床恶化的一种潜在解释 合并MDD/CUD的结果是，CUD，大麻戒断的两个主要贡献者 通过添加MDD可以增强症状和压力。这是由于重叠而假设的 在大麻戒断和MDD症状以及患有患者的压力反应增强中 单独的MDD相对于神经型个体。大麻戒断和压力反应都受到 内源性大麻素（ECB）系统；已经在中央（大脑）和 外围（血液）。因为欧洲央行系统与这些重复的主要贡献者有关，所以 它为成瘾药物疗法的发展提供了潜在的靶标。此外，欧洲央行 与神经型个体相比，在MDD患者中观察到的失调失调表明欧洲央行调节 单独使用CUD的人可能会有更多的效用。但是，目前是 尚不清楚欧洲央行系统是否相对于CUD在合并症的MDD/CUD中唯一失调（AIM 1），如果仅相对于CUD（AIM 2）或 如果合并症MDD/CUD与仅相对于CUD的应力响应增强相关（AIM 3）。到 解决这些目标，将招募三十名成年人（15个CUD，15 MDD/CUD）完成四个面对面的人 实验室访问超过一周。第一次访问将在大麻使用时完成， 急性撤离期间将进行剩下的三次访问。血液样本将在三个时间点收集 在每次访问期间评估欧洲央行的音调和参与者将完成大麻戒断症状 一周内多个时间点的评估。在研究的最后一天，参与者将 经过社会压力测试。压力和毒品渴望的主观经历，客观的生物标志物 在压力暴露之前和在 此后四个时间点。拟议项目的结果将用于确定相关性 欧洲央行调制作为合并症MDD/CUD的药物治疗策略 临床试验开发。在拟议项目的整个过程中，申请人（Erin Martin）将收到 转化研究关键方面的指导，包括研究设计和实施，科学 沟通和高级统计分析。该培训将应用于未来的发展 独立研究计划，研究精神病患者的成瘾。