Effects of Zolpidem Extended-Release on Withdrawal and Sleep in Cannabis Users

描述(申请人提供)：自1990年中期S以来，因大麻相关问题而入院治疗的人数增加了一倍多。临床试验表明，大多数因大麻问题而接受治疗的人复发，复发率与观察到的其他滥用药物的复发率相当。目前还没有公认的治疗大麻依赖的药物疗法。在以前的研究中，屈诺比诺(Marinol(R))显示出了治疗大麻依赖的潜力，但这些研究涉及每天给药3-5次，这引起了人们对认知和精神运动能力的潜在损害、用药依从性和转移的可能性的一些担忧。本提案将通过检查睡前给药的唑吡坦缓释剂(Ambien CR(R))对大麻戒断严重程度、客观睡眠措施和副作用的影响，来扩展先前关于治疗大麻使用障碍的药物开发的研究。之所以选择这种药物进行研究，是因为它已经被证明可以扭转睡眠问题，这是大麻戒断的一个突出症状，而且睡眠研究表明，改善睡眠功能障碍可能会导致其他大麻戒断效果的减弱，如焦虑、抑郁和愤怒。这一系列研究也很有吸引力，因为与屈诺比诺相比，唑吡坦和其他几种安眠药据称副作用更少，滥用可能性更小，然而，这些影响尚未在大麻使用者的对照研究中进行评估。这项拟议的实验将仔细研究唑吡坦(12.5毫克)和安慰剂在短暂的突然大麻戒断期间对每天吸食大麻的人的影响。采用受试者内部交叉设计，参与者将依次完成临时吸食大麻、用药突然戒烟和在下一个戒断期之前恢复到基线的阶段。在研究的每个阶段，每天都会对大麻戒断严重程度、睡眠多导图(PSG)、一系列最先进的认知和精神运动测试的表现以及药物副作用的主观评级进行评估。这项实验的结果将提供关于已知的改善睡眠功能的药物是否是用于治疗大麻依赖的药物疗法的安全和有效的替代屈诺比诺的初步信息，并将提供关于长期使用大麻和戒断对睡眠结构影响的新数据。 公共卫生承诺：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。这项研究旨在调查FDA批准的安眠药唑吡坦缓释片(Ambien CR(R))减少与停止每日使用大麻有关的戒断效应的能力，并仔细研究大麻戒断对睡眠功能的影响以及与该药物相关的安全风险和副作用的发生。

DESCRIPTION (provided by applicant): Treatment admissions for cannabis-related problems have more than doubled since the mid 1990's. 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 for treating cannabis dependence. Dronabinol (Marinol(r)) has exhibited effects in prior studies suggesting potential for treating cannabis dependence, but these studies involved dronabinol administration 3-5 times per day, which raises some concerns with regards to potential impairment of cognitive and psychomotor abilities, medication adherance, and potential for diversion. The present proposal will extend previous research on medications development for the treatment of cannabis use disorders by examining the effects of zolpidem extended-release (Ambien CR(r)) administered at bedtime on cannabis withdrawal severity, objective sleep measures, and presence of side-effects. This medication was selected for study because it has been demonstrated to reverse sleep problems, a prominent symptom of cannabis withdrawal, and sleep research suggests that it is possible that amelioration of sleep dysfunction may result in an attenuation of other cannabis withdrawal effects such as anxiety, depression, and anger. This line of research is also attractive because zolpidem and several other sleep medications are purported to have fewer side effects and less abuse liability compared with dronabinol, however, these effects have not been assessed in controlled studies of cannabis users. The proposed experiment will carefully study the effects of zolpidem (12.5mg) and placebo in daily cannabis users during brief periods of abrupt cannabis abstinence. Using a within-subjects crossover design, participants will sequentially complete periods of baseline ad-libitum cannabis smoking, abrupt cannabis abstinence with medication, and a return to baseline prior to the next abstinence period. Cannabis withdrawal severity, sleep polysomnography (PSG), performance on a comprehensive battery of state-of-the-art cognitive and psychomotor tests, and subjective ratings of medication side effects will be assessed daily in each phase of the study. Outcomes from this experiment will provide initial information regarding whether medications known to improve sleep function are safe and effective alternatives to dronabinol for use as pharmacotherapies in the treatment of cannabis dependence, and will provide new data regarding the effects of chronic cannabis use and withdrawal on sleep architecture. PUBLIC HEALTH RELEVEANCE: 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. This research is designed to investigate the ability of the FDA approved sleep medication zolpidem extended-release (Ambien CR(r)) to reduce the withdrawal effects associated with stopping daily marijuana use, and to carefully study the effects of quitting marijuana on sleep functioning and the occurance of safety risks and side-effects associated with the medication in marijuana users.