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

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。先前的研究表明，口服屈诺比诺(THC)可显著减轻大麻戒断症状和吸烟大麻的急性影响。这些效果表明，屈诺比诺可能是治疗大麻依赖的有用辅助干预措施。然而，到目前为止，只有一项研究专门比较了多剂量屈奴比诺对评估临床疗效重要的结果。此外，关于长期服用大麻的人的认知、精神运动和主观副作用的数据相对匮乏。拟议研究的具体目的是复制和扩大关于屈诺麻酚对大麻戒断严重程度、认知和精神运动表现、吸烟大麻的急性影响以及大麻自我给药的影响的研究。实验一将仔细研究屈诺比诺(安慰剂，10，20，40 mg，tid)的剂量效应。每天吸食大麻的人。使用受试者内设计，参与者将在临时吸食大麻的时期和戒除大麻的时期之间交替使用屈诺比诺。将在多个时间点评估大麻戒断严重程度、在一系列最先进的认知和精神运动测试中的表现、对吸烟大麻的反应以及药物副作用的评级。实验2将研究屈诺比诺(安慰剂，20，40 mg，tid。)的作用。关于大麻在即兴和限制使用选择测试期间的自我给药行为。参与者将在3个平衡期内维持每种剂量的屈诺比诺，每个平衡期为期12天。在上述每个时期内，将在以下两个随机时期对大麻使用行为进行评估：1)随意吸食大麻；2)限制吸食大麻；在此期间，参与者必须在吸食大麻或接受不同数额的金钱之间做出不同的选择。安慰剂和活性大麻的情况将包括在内，以帮助解释和评估结果的有效性。这两项实验将扩大目前对大麻使用者行为药理学的了解，并将有助于了解是否应考虑将屈诺麻酚用于临床治疗大麻使用障碍，以及应考虑以何种剂量使用屈诺麻酚。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。这项研究旨在确定FDA批准的药物Dronabinol(Marinol(R))是否具有有助于人们更容易停止日常使用大麻的效果，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.