Buspirone Treatment for Marijuana Dependence

描述(申请人提供)：大麻是美国最常用的非法药物。尽管大麻的使用和潜在的健康后果很普遍，关于大麻的基础科学研究也很发达，但很少有研究侧重于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-HT1A[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，我们建议对大麻依赖者进行丁螺环酮的双盲随机试验。应急管理(CM)干预和动机增强疗法(MET)将结合在一起，以鼓励学习投入和保留。我们假设，与接受安慰剂治疗合并MET和CM的患者相比，接受丁螺环酮联合MET和CM治疗的患者将改善大麻使用结果。此外，由于5-HT1A受体的遗传变异已被发现，并可能改变对丁螺环酮的反应，我们建议提取基因组DNA，根据与5-HT1A受体活性相关的基因的多态性来表征受试者。我们假设，5-HT1a受体功能缺陷的患者的治疗结果将比5-HT1a受体功能缺陷的患者差。最后，由于可靠的依从性评估对于解释结果措施至关重要，我们建议将开发和验证丁螺环酮(6-羟基-丁螺环酮)的主要代谢物的分析作为次要目标来衡量治疗的依从性。这项研究的结果可能会导致开发一种治疗大麻依赖的新药物疗法，增加我们对预测结果的潜在遗传生物标志物的了解，并改进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疗法。这项研究将评估丁螺环酮在减少大麻依赖成年人使用大麻方面的效果。将纳入应急管理干预和动机增强疗法，以鼓励学习投入和保留。将使用一种测定丁螺环酮主要代谢物血清水平的方法来衡量依从性，并将提取基因组DNA，根据可能与丁螺环酮活性相关的基因的多态来表征受试者。

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.