Buspirone Treatment for Marijuana Dependence

描述（由申请人提供）：大麻是美国最常用的非法药物。虽然大麻的使用和潜在的健康后果很普遍，而且关于大麻素的基础科学研究也很发达，但很少有研究关注大麻使用障碍的临床治疗。丁螺环酮是一种部分5-羟色胺1-A（5-HT 1A [5-羟色胺1A]）受体激动剂，在初步试验中显示出减少大麻使用的希望。因此，我们提出了一个双盲随机试验丁螺环酮在大麻依赖的个人。将纳入应急管理（CM）干预和动机增强治疗（MET），以鼓励参与和保留研究。我们假设，与接受安慰剂治疗结合MET和CM的个体相比，接受丁螺环酮治疗结合MET和CM的个体将改善大麻使用结果。此外，由于5-HT 1A受体的遗传变异已被确定，并可能改变丁螺环酮的反应，我们建议提取基因组DNA，根据与5-HT 1A受体活性相关的基因多态性来表征受试者。我们假设5-HT 1A受体功能缺陷的个体比5-HT 1A受体无功能缺陷的个体具有更差的治疗结果。最后，作为一个可靠的评估的依从性是至关重要的结果措施的解释，我们建议作为一个次要目标，开发和验证丁螺环酮（6-羟基-丁螺环酮）的主要代谢产物的测定，以衡量治疗的依从性。这项研究的结果可能会导致开发一种新的大麻依赖药物疗法，增加我们对预测结果的潜在遗传生物标志物的了解，并改善大麻依赖调查的临床试验方法。. 公共卫生相关性：大麻是最常用的非法药物，但很少有临床试验评估大麻依赖的药物治疗。这项研究将评估丁螺环酮减少大麻依赖成年人大麻使用的疗效。将纳入应急管理干预和动机增强治疗，以鼓励参与和保留研究。将采用测定丁螺环酮主要代谢物血清水平的试验来测量依从性，并将提取基因组DNA，根据可能与丁螺环酮活性相关的基因多态性来表征受试者。

DESCRIPTION (provided by applicant): Marijuana is the most commonly used illicit drug in the United States. Although its use and potential health consequences are widespread and basic science research on cannabinoids is well developed, little research has focused on the clinical treatment of marijuana use disorders. Buspirone, a partial serotonin 1-A (5-HT1A [5-hydroxytryptamine1A]) receptor agonist, has shown promise for reducing marijuana use in preliminary trials. Accordingly, we propose a double-blind randomized trial of buspirone in marijuana-dependent individuals. A contingency management (CM) intervention coupled with motivational enhancement therapy (MET) will be incorporated to encourage study engagement and retention. We hypothesize that individuals who receive buspirone treatment combined with MET and CM will have improved marijuana use outcomes compared to individuals receiving a placebo treatment combined with MET and CM. Further, as genetic variations in 5-HT1A receptors have been identified, and may alter the response to buspirone, we propose to extract genomic DNA to characterize subjects according to polymorphisms of genes relevant to 5-HT1A receptor activity. We hypothesize that individuals with functionally deficient 5-HT1A receptors will have poorer treatment outcomes than individuals without functional deficiency at the 5-HT1A receptor. Finally, as a reliable assessment of compliance is critical to interpretation of outcome measures, we propose as a secondary aim to develop and validate an assay of a major metabolite of buspirone (6-hydroxy-buspirone) to measure compliance with treatment. Results from this study could lead to the development of a new pharmacotherapy for marijuana dependence, increase our knowledge of a potential genetic biomarker for prediction of outcomes, and improve clinical trial methodology in the investigation of marijuana dependence. . PUBLIC HEALTH RELEVANCE: Marijuana is the most commonly used illicit drug, yet few clinical trials have evaluated pharmacotherapy treatments for marijuana dependence. This study will evaluate the efficacy of buspirone for reducing marijuana use in marijuana-dependent adults. A contingency management intervention and motivational enhancement therapy will be incorporated to encourage study engagement and retention. An assay determining serum levels of a major metabolite of buspirone will be employed to measure compliance, and genomic DNA will be extracted to characterize subjects according to polymorphisms of genes potentially relevant to the activity of buspirone.