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

基本信息

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
项目类别：
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

项目摘要

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.

去年使用过大麻的人中有近五分之一患有大麻使用障碍（CUD），近三分之一的 CUD 患者同时患有重度抑郁症 (MDD)。共病 MDD/CUD 与较高的成瘾治疗寻求率和较差的治疗结果相关相对于单独的 CUD。然而，对于 CUD 尚无可用的药物治疗，临床试验也很少针对共病 MDD/CUD 的治疗尚未成功。临床恶化的一种可能解释合并 MDD/CUD 的结果是 CUD 复发的两个主要因素，即大麻戒断添加 MDD 可能会增强症状和压力。这是由于重叠而假设的大麻戒断和抑郁症症状以及在患有抑郁症的人中观察到的应激反应增强单独的 MDD 相对于神经典型个体。大麻戒断和应激反应均受调节内源性大麻素（ECB）系统；中枢（大脑）和外周（血液中）。因为 eCB 系统与这些复发的主要因素有关，它为成瘾药物治疗的发展提供了潜在的目标。此外，欧洲央行与神经正常个体相比，MDD 患者观察到的失调表明 eCB 调节相对于单独的 CUD，对于患有 MDD/CUD 共病的患者可能具有额外的效用。然而，目前未知相对于单独的 CUD，ECB 系统在共病 MDD/CUD 中是否存在独特的失调（目标 1)，如果相对于单独的 CUD，合并 MDD/CUD 的大麻戒断严重程度增强（目标 2），或相对于单独的 CUD，共病 MDD/CUD 是否与应激反应增强相关（目标 3）。到为了实现这些目标，将招募 30 名成年人（15 CUD、15 MDD/CUD）来完成四项面对面的课程实验室访问超过一周。第一次访问将在照常使用大麻期间完成，并且其余 3 次就诊将发生在急性戒断期间。将在三个时间点采集血液样本在每次访问期间评估 eCB 语气，参与者将完成大麻戒断症状一周内多个时间点的评估。在研究参与的最后一天，参与者将接受社会压力测试。压力和药物渴望的主观体验，客观生物标志物压力（例如血液皮质醇和心率）以及血液 eCB 将在压力暴露之前和压力暴露时收集之后的四个时间点。拟议项目的成果将用于确定相关性未来背景下 eCB 调节作为 MDD/CUD 共病的药物治疗策略临床试验开发。在拟议项目的过程中，申请人（艾琳·马丁）将收到在转化研究的关键方面提供指导，包括研究设计和实施、科学沟通和高级统计分析。此次培训将应用于未来的发展独立研究计划检查患有精神共病的人的成瘾情况。