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

越来越多的医疗法律和社会文化对大麻使用的容忍正在推动大麻的增加 可获得性/使用率，尽管有科学证据表明，经常使用大麻会带来健康风险。吸食大麻 精神障碍(CUD)是最常见的治疗药物滥用问题，而且不断升级的大麻 可获得性/使用量可能会增加对治疗的需求。目前还没有得到批准的治疗CUD的药物， 行为治疗后复发率高。尽管迫切需要药物学和 心理社会干预，最佳治疗应该建立在对机制的清楚理解的基础上 这是大麻使用的基础。尽管临床上认为暴露在与毒品有关的线索中 线索暴露与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，欲望在多大程度上调节了这种联系 被检查过了。这项拟议的研究旨在建立一个人体实验室模型，以检验 关于寻找毒品的线索暴露(以大麻为样本)和渴望在 提示/寻找联系。线索诱导的搜索将在不同的单价的背景下进行考察(使用 累进比率表)，以获得大麻，引入可变性的毒品动机和不同 环境条件。这一混合线索-暴露+选择程序模型将被用来检验 N-乙酰半胱氨酸(NAC)是一种半胱氨酸前体药物，可以减轻与大麻线索相关的渴望和寻找。在这 安慰剂对照，受试者内，随机交叉，住院研究，共有32名患有CUD的患者 将在接触大麻和中性线索之前给予NAC(0vs2400 Mg)。我们的主要成果 衡量标准是使用大麻(与金钱)选择来评估寻找大麻的行为，公关任务。在每一个中 会议期间，参与者将有11个选择机会为吸食大麻的烟头工作(7.0% THC；最多11次泡芙)或金钱替代(最多22美元)。目的是确定是否：(1)陈述 与大麻相关的多感官线索与中性线索相比，增加了对大麻的寻求；(2)Glu探测器NAC 减弱大麻相关线索对渴望和寻找的影响；以及，(3)大麻线索诱导 渴求在线索暴露对药物寻找的影响中起中介作用。总体而言，这个项目将增加机械性 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CUD的健康负担。该项目解决了一个重大的公共卫生问题 并采取强有力的方法，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.