Cue Reactivity Model/Pharm. Intervention in Cannabis Use

描述(申请人提供)：大麻是美国最常用的非法药物，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，复发率很高，与其他物质使用障碍的复发率相当。因此，显然有必要选择治疗方法，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，大多数研究的目标是减轻大麻的戒断症状。鉴于渴望是大多数滥用大麻的人报告的一种现象，而且被认为与长期滥用和复发有关，因此减轻渴望也应该是推定的药物治疗的重点。目前，还没有经过验证的实验室模型来评估药理化合物减少大麻欲望的有效性。目前的申请提出了开发和测试大麻线索反应范例所必需的研究，该范例能够在受控的实验室环境中成功地诱导和定量测量对大麻的渴望。在这个模型中，比较了大麻依赖者对大麻相关线索(例如，用具)和对与毒品无关(即中性)线索的主观和生理反应。许多实验室研究表明，这种模式使用与滥用药物有关的线索，包括酒精、可卡因、鸦片和尼古丁，会引起强烈的渴望。它还没有用大麻线索进行测试，因此大麻线索诱导的反应性的特异性尚不清楚。我们建议建立大麻线索反应范式的特异性，然后使用典型的大麻素激动剂-9-四氢大麻酚(口服THC)来测试该模型的敏感性。如果这些初步和探索性研究表明线索反应性范式既特异又敏感，那么就可以自信地使用它来检验用某些化合物预处理是否可以减轻对大麻相关线索的渴望和反应性。这一范例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。它还将有助于测试与循证行为干预相结合的药物治疗，这些干预措施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.