Cue Reactivity Model/Pharm. Intervention in Cannabis Use

描述（由申请人提供）：大麻是美国最常用的非法毒品，超过200万美国人滥用或依赖这种药物。对治疗的需求正在增加，治疗结果研究表明复发率与其他物质使用障碍相当。因此，显然需要治疗方案，特别是作为标准行为策略的辅助手段。最近，开发一种减少使用和（或）防止复发的药物已成为研究的重点，其中大多数研究的目标是减轻大麻戒断症状。考虑到渴望是大多数滥用大麻的人报告的一种现象，并且被认为与滥用的持续和复发有关，减少渴望也应该是假定药物的重点。目前还没有经过验证的实验室模型来评估药物化合物减少大麻渴望的功效。目前的应用程序提出了必要的研究，以开发和测试大麻线索反应性范式，该范式能够在受控的实验室环境中成功诱导和定量测量大麻渴望。在这个模型中，比较了大麻依赖个体对大麻相关线索（例如，用具）和药物无关线索（例如，中性）的主观和生理反应。大量的实验室研究表明，这种模式引发了强烈的渴望，使用与滥用药物有关的线索，包括酒精、可卡因、阿片类药物和尼古丁。它还没有被大麻线索测试过，因此大麻线索引起的反应的特异性尚不清楚。我们建议建立大麻线索反应性范式的特异性，然后使用原型大麻素激动剂测试该模型的敏感性。9-四氢大麻酚（口服THC）。如果这些初步的和探索性的研究表明线索反应范式是特异性的和敏感的，那么它就可以自信地用来检验用某些化合物预处理是否可以减弱对大麻相关线索的渴望和反应。这种模式将有助于在进行昂贵和耗时的临床试验之前确定最有希望的药物。它还将有助于测试药物治疗与循证行为干预相结合的情况，这些干预有可能导致大麻使用障碍的成功综合治疗。

DESCRIPTION (provided by applicant): Marijuana is the most commonly used illegal drug in the United States, and more than 2 million Americans are abusing or dependent on the drug. Demand for treatment is increasing, and treatment outcome studies indicate high relapse rates that are comparable to those of other substance use disorders. Thus, there is a clear need for treatment options, particularly as adjuncts to standard behavioral strategies. The development of a medication to reduce use and/or prevent relapse recently has become a focus of research, most of which targets the alleviation of cannabis withdrawal symptoms. Given that craving is a phenomenon reported by the majority of individuals who abuse marijuana, and is thought to be related both to the perpetuation of abuse and to relapse, the attenuation of craving also should be a focus of putative medications. Currently there are no validated laboratory models to evaluate the efficacy of a pharmacologic compound to reduce marijuana craving. The current application proposes studies that are necessary to develop and test a marijuana cue reactivity paradigm that enables the successful induction and quantitative measurement of marijuana craving in a controlled laboratory setting. In this model, subjective and physiological responses both to marijuana-related cues (e.g., paraphernalia) and to drug unrelated (i.e., neutral) cues are compared in cannabis dependent individuals. Numerous laboratory studies show this paradigm elicits robust craving using cues associated with drugs of abuse including alcohol, cocaine, opiates, and nicotine. It has not been tested with marijuana cues, thus the specificity of marijuana cue-induced reactivity is not known. We propose to establish the specificity of the marijuana cue reactivity paradigm, and then to test the sensitivity of the model using a prototypic cannabinoid agonist, ?9-tetrahydrocannabinol (oral THC). If these preliminary and exploratory studies indicate that the cue reactivity paradigm is both specific and sensitive, it can then be used with confidence to examine whether pretreatment with certain compounds can attenuate craving and reactivity to marijuana-related cues. This paradigm will help identify the most promising medications prior to undertaking expensive and time-consuming clinical trials. It will also be useful in the testing of pharmacologic treatments in combination with evidence-based behavioral interventions that have the potential to lead to successful integrative treatment for cannabis use disorders.