Efficacy and Safety of Dronabinol (Oral THC) for Treating Cannabis Dependence

描述（由申请人提供）：自20世纪90年代中期以来，大麻相关问题的治疗入院人数增加了一倍多。临床试验表明，大多数因大麻问题接受治疗的人都会复发，复发率与观察到的其他滥用药物的复发率相当。目前没有公认的治疗大麻依赖的药物疗法。在先前的研究中，屈大麻酚（口服四氢大麻酚）的给药已被证明可显著减轻大麻戒断症状和吸食大麻的急性影响。这些影响表明，屈大麻酚可能是一种有用的辅助干预治疗大麻依赖。然而，迄今为止，只有一项研究专门比较了多剂量屈大麻酚对评估临床疗效的重要结果。此外，关于常规大麻使用者长期服用屈大麻酚的认知、精神运动和主观副作用的数据相对缺乏。拟议研究的具体目标是复制和扩展关于屈大麻酚对大麻戒断严重程度、认知和精神表现、吸食大麻的急性影响以及大麻自我给药的影响的研究。实验1将仔细研究屈大麻酚（安慰剂，10，20，40 mg t.i.d.）每天吸食大麻的人使用受试者内设计，受试者将在自由吸食大麻的时期和使用屈大麻酚维持的大麻戒断时期之间交替。将在多个时间点评估大麻戒断严重程度、最先进的认知和心理测试综合组合的表现、对吸食大麻的反应以及药物副作用的评级。实验2将研究屈大麻酚（安慰剂，20，40 mg t.i.d.）在自由和限制进入选择测试期间大麻自我管理行为。受试者将在3个平衡期内维持每种屈大麻酚剂量条件，每个平衡期持续12天。在每个阶段内，大麻使用行为将在以下随机阶段进行评估：1）随意使用大麻，2）限制使用大麻，在此期间，参与者必须在吸食大麻或接受可变金额的金钱之间做出离散选择。将纳入安慰剂和活性大麻条件，以帮助解释和评估结果的有效性。这两项实验将扩展大麻使用者中屈大麻酚行为药理学的现有知识，并将有助于告知是否应考虑将屈大麻酚用于治疗大麻使用障碍的临床用途以及剂量。公共卫生相关性：寻求治疗大麻相关问题的人数正在增加，但目前还没有被证明可以帮助他们戒烟的药物。这项研究旨在确定FDA批准的药物屈大麻酚（Marinol（R））是否具有可能有助于人们更容易停止日常大麻使用的效果，并仔细研究不同剂量药物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. Administration of dronabinol (oral THC) has been shown to significantly attenuate cannabis withdrawal symptoms and the acute effects of smoked cannabis in prior studies. These effects suggest that dronabinol might be a useful adjunct intervention for treating cannabis dependence. However, only one study to date has specifically compared multiple doses of dronabinol on outcomes that are important for assessing clinical efficacy. Moreover, there is a relative dearth of data regarding the cognitive, psychomotor, and subjective side effects of chronic dronabinol administration in regular cannabis users. Specific aims of the proposed research are to replicate and extend research on the effects of dronabinol on cannabis withdrawal severity, cognitive and psychomotor performance, the acute effects of smoked cannabis, and cannabis self-administration. Experiment 1 will carefully study the dose effects of dronabinol (placebo, 10, 20, 40mg t.i.d.) in daily cannabis users. Using a within subjects design, participants will alternate between periods of ad-libitum cannabis smoking and periods of cannabis abstinence with dronabinol maintenance. Cannabis withdrawal severity, performance on a comprehensive battery of state-of-the-art cognitive and psychomotor tests, response to smoked cannabis, and ratings of medication side effects will be assessed at multiple timepoints. Experiment 2 will study the effects of dronabinol (placebo, 20, 40mg t.i.d.) on cannabis self-administration behavior during ad-libitum and restricted access choice tests. Participants will be maintained on each dronabinol dose condition in 3 counterbalanced periods lasting 12 days each. Within each of these periods, cannabis use behavior will be assessed during randomly periods of 1) ad-libitum cannabis access, and 2) restricted access during which participants must make discrete choices between smoking cannabis or receiving variable amounts of money. Placebo and active cannabis conditions will be included in order to help interpret and assess the validity of outcomes. These two experiments will extend the current knowledge of the behavioral pharmacology of dronabinol in cannabis users and will help inform whether, and at what doses, dronabinol should be considered for clinical use in the treatment of cannabis use disorders. 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. This research is designed to determine whether the FDA approved medication dronabinol (Marinol(R)) has effects that might help make it easier for people to stop daily marijuana use, and to carefully study the occurance of safety risks and side-effects at different doses of the drug.