Role of Sleep in the Treatment of Cannabis Dependence

描述(由申请人提供)：去年约有120万美国人因大麻使用障碍而接受治疗。临床试验表明，大多数接受大麻问题治疗的人会复发，复发率与观察到的其他滥用药物的复发率相当。目前，还没有公认的药物疗法来帮助治疗大麻使用障碍。睡眠障碍是大麻戒断综合症最突出的症状之一，最近的实验室研究表明，大量吸食大麻的人在突然停止使用后会出现临床上严重的睡眠问题。具体地说，来自临床调查和前瞻性实验室研究的数据表明，戒烟期间的睡眠障碍可能会促使人们重新吸食大麻，而大量吸食大麻的人在戒烟期间表现出睡眠结构和连续性的中断，符合诊断失眠的基准标准。已知在戒除其他滥用药物期间也会出现类似的戒断对睡眠的影响和与睡眠相关的复发风险，而且重要的是，研究表明，在酒精治疗计划中增加改善睡眠的干预措施可以显著改善临床结果。这表明，改善睡眠的干预措施可以减少试图戒烟的大麻使用者的复发。拟议的项目旨在解决在了解睡眠和大麻使用之间的关系方面存在的两个重要差距：1)没有对寻求治疗的大麻使用者进行前瞻性或客观的戒断引起的睡眠障碍评估，因此，回顾调查和实验室研究的外部有效性不确定；2)尚不清楚戒烟期间改善睡眠障碍是否会改善临床结果(例如，预防复发)。这项拟议的研究将是一项双盲门诊临床试验，符合条件的参与者将接受两种为期12周的治疗干预措施之一：1)心理社会治疗(MET/CBT)+12.5毫克缓释唑吡坦，或2)MET/CBT+安慰剂。当参与者试图在他们的家庭环境中戒除大麻时，将在整个研究过程中获得睡眠质量和结构的客观和主观测量。睡眠评估包括多导睡眠图(摄入量、治疗第1周、第6周、第10周和第12周，以及3个月的随访)、活动图(每天)和睡眠日记(每天)。参与者将每周完成一次MET/CBT治疗单元，完成评估并提供观察到的尿样进行毒理学测试，并在治疗期间每晚自我给药。我们相信缓释唑吡坦将使研究参与者受益的机制是改善睡眠。睡眠和大麻使用结果之间的关系将通过有计划的调解分析来确定。这项研究的结果将有助于为大麻使用障碍的治疗提供信息，将扩大对大麻使用和睡眠相互关系的科学理解，并将有助于指导未来的药物治疗研究。 与公共卫生相关：寻求大麻相关问题治疗的人数正在上升，但目前还没有公认的药物可以帮助他们戒烟。经常吸食大麻的人报告说，当他们试图戒烟时，他们会睡不着觉，而睡眠不足可能会导致复发。这项研究旨在衡量人们在试图戒除大量吸食大麻时睡眠问题的严重性，并调查FDA批准的安眠药--缓释唑吡坦(Ambien CR(R))在试图戒除大麻的人中提高戒烟率的能力。

DESCRIPTION (provided by applicant): Approximately 1.2 million Americans were admitted to treatment for cannabis use disorders last year. Clinical trials indicate that a majority of those who enter treatment for cannabis problems relapse, and relapse rates are comparable to those observed for other drugs of abuse. Currently, there are no accepted pharmacotherapies to aid the treatment of cannabis use disorders. Disturbed sleep is one of the most prominent symptoms of the cannabis withdrawal syndrome, and recent laboratory research has demonstrated that heavy cannabis users experience clinically significant sleep problems following abrupt cessation of use. Specifically, data from clinical surveys and prospective laboratory studies suggest that sleep disturbance during abstinence can precipitate relapse to cannabis use, and heavy cannabis users exhibit disruptions in sleep architecture and continuity during abstinence that meet benchmark criteria for a diagnosis of insomnia. Similar abstinence induced effects on sleep and sleep-related risk of relapse are known to occur during withdrawal from other drugs of abuse, and, importantly, research has shown that adding sleep improvement interventions to alcohol treatment programs can significantly improve clinical outcomes. This suggests that sleep improvement interventions could reduce relapse among cannabis users trying to quit. The proposed project aims to address two important gaps in understanding the relationship between sleep and cannabis use: 1) abstinence-induced sleep disturbance has not been assessed prospectively or objectively in cannabis users seeking treatment, thus, the external validity of retrospective surveys and laboratory studies is uncertain and 2) it is unclear if amelioration of sleep disturbance during a quit attempt will result in improved clinical outcomes (e.g. relapse prevention). The proposed study will be a double blind outpatient clinical trial in which eligible participants will receive one of two 12-week treatment interventions: 1) psychosocial therapy (MET/CBT) + 12.5 mg extended-release zolpidem, or 2) MET/CBT + placebo. Objective and subjective measures of sleep quality and architecture will be obtained throughout the study while participants attempt to quit use of cannabis in their home environment. Sleep assessments include polysomnography (intake, treatment weeks 1, 6, 10, and 12, and 3 month follow- up), actigraphy (daily) and sleep diaries (daily). Participants will complete MET/CBT therapy modules once per week, complete assessments and provide observed urine specimens for toxicological testing twice weekly, and self-administer study medication nightly during treatment. The mechanism by which we believe extended- release zolpidem will benefit study participants is an improvement in sleep. The relationship between sleep and cannabis use outcomes will be determined via planned mediation analysis. Outcomes from this study will help inform the treatment of cannabis use disorders, will extend the scientifi understanding of the interrelationship of cannabis use and sleep, and will help guide future pharmacotherapy research. PUBLIC HEALTH RELEVANCE: The number of people seeking treatment for marijuana-related problems is on the rise, yet there is no currently accepted medication proven to help them quit. Frequent marijuana users have reported that they have trouble sleeping when they try to quit, and that the loss of sleep can lead to relapse. This research is designed to measure the severity of sleep problems in people as they are trying to quit heavy use of marijuana, and to investigate the ability of an FDA approved sleep medication, extended-release zolpidem (Ambien CR(R)), to improve quit rates among people trying to stop using marijuana.