Marijuana Cue-Reactivity and Seeking Behavior in Regular Cannabis Users: Pilot Test of Glutamatergic Modulation

越来越多的医学法律和社会文化对大麻使用的容忍正在助长大麻的增长 尽管有科学证据表明经常使用大麻会带来健康风险，但大麻的可用性/使用率仍然很高。大麻使用 疾病（CUD）是最常见的治疗药物滥用问题， 供应/使用可能会增加对治疗的需求。没有批准的药物治疗CUD， 行为治疗后复发率很高。尽管迫切需要药理学和 心理社会干预，最佳的治疗方法应基于对机制的明确理解 大麻使用的潜在原因尽管临床上普遍认为接触毒品相关的线索 暗示了吸毒，但线索暴露和吸毒之间的因果关系尚未得到证实 在实验控制的条件下。同样，渴望在多大程度上调解了这种联系， 被检查过了该研究旨在建立一个人类实验室模型，以检查 线索暴露在药物寻求（使用大麻作为一个例子）和渴望的贡献， cue/seeking connection.线索诱导寻求将在不同的单位价格的背景下进行研究（使用 渐进比例计划）获得大麻，引入药物动机的可变性和不同的 环境条件这个混合线索暴露+选择程序模型将被用来测试是否 N-乙酰半胱氨酸（NAC），一种半胱氨酸前药，减弱大麻线索相关的渴望和寻求。在这 安慰剂对照、受试者内、随机交叉、住院研究，共32例CUD患者 将在大麻和中性线索暴露之前给予NAC（0 vs 2400 mg）。我们的主要成果 测量是大麻寻求行为评估使用大麻（与金钱）的选择，公关任务。在每个 会议，参与者将有11个选择机会，从大麻香烟（7.0%）的喷烟工作 THC;最多11喷）或货币替代品（最多22美元）。目的是确定是否：（1）介绍 多感官大麻相关与中性线索增加大麻寻求;（2）Glu探针NAC 减弱大麻相关线索对渴望和寻求的影响;和，（3）大麻线索诱导 渴求感介导线索暴露对药物寻求的影响。总体而言，该项目将增加机械性 了解线索诱导的大麻使用，并为筛选治疗方法提供一个模型， 减轻慢性腹泻的健康负担。该项目以创新的方式解决了一个重大的公共卫生问题。 这将对实地产生重大和持续的影响。

Growing medico-legal and socio-cultural tolerance of marijuana use is fueling a rise in marijuana availability/use despite scientific evidence that regular marijuana use carries health risks. Cannabis use disorder (CUD) is the most commonly treated substance abuse problem, and escalating marijuana availability/use is likely to increase demand for treatment. There is no approved medication to treat CUD, and relapse rates after behavioral treatment are high. Despite an urgent need for pharmacological and psychosocial interventions, optimal treatments should be predicated on clear understanding of mechanisms that underlie marijuana use. Although it is clinically accepted that exposure to drug-related cues foreshadows drug taking, a causal link between cue-exposure and drug use has yet to be demonstrated under experimentally controlled conditions. Similarly, the extent to which craving mediates this link has not been examined. The proposed study aims to establish a human laboratory model to examine the effect of cue exposure on drug seeking (using marijuana as an exemplar) and the contribution of craving in the cue/seeking connection. Cue-induced seeking will be examined in the context of varying unit price (using a progressive ratio schedule) to obtain marijuana, to introduce variability in drug motivation and different environmental conditions. This hybrid cue-exposure + choice procedure model will be used to test whether N-acetylcysteine (NAC), a cysteine pro-drug, attenuates marijuana cue-related craving and seeking. In this placebo-controlled, within subject, randomized crossover, inpatient study, a total of 32 individuals with CUD will be administered NAC (0 vs 2400 mg) prior to marijuana and neutral cue exposure. Our primary outcome measure is marijuana-seeking behavior assessed using a marijuana (vs. money) choice, PR task. In each session, participants will be given 11 choice opportunities to work for puffs from a marijuana cigarette (7.0% THC; max of 11 puffs) or money alternative (max of $22). Aims are to determine whether: (1) presentation of polysensory marijuana-related vs. neutral cues increases marijuana seeking; (2) the Glu probe NAC attenuates the effects of marijuana-related cues on craving and seeking; and, (3) marijuana cue-induced craving mediates effects of cue exposure on drug seeking. Overall, this project will increase mechanistic understanding of cue-induced cannabis use and provide a model for screening therapeutic approaches to reduce health burdens of CUD. This project addresses a significant public health problem with an innovative and strong approach, and will have a substantial and sustained impact on the field.