Cue Reactivity Model/Pharm. Intervention in Cannabis Use

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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.