Vilazodone 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。临床前和临床研究表明大麻素与5-羟色胺系统之间存在相互作用。维拉唑酮是一种结合了5-羟色胺再摄取抑制和5-HT1A部分激动剂的化合物，最近已上市。鉴于其双重的5-羟色胺能作用机制，维拉唑酮可能有希望作为大麻依赖的治疗方法。因此，我们建议在大麻依赖的成年人中进行维拉唑酮的随机、安慰剂对照试验。应急管理干预与激励增强疗法将结合在一起，以鼓励学习投入和保留。此外，还将提取基因组DNA，根据与5-HT1A受体活性相关的基因的多态，特别是C-(1019)G变种来确定受试者的特征。我们假设，与接受安慰剂治疗合并MET和CM的患者相比，接受维拉唑酮联合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，并可能改变对维拉唑酮的反应，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。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，并增加我们对预测结果的潜在遗传生物标志物的了解。。 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。这项研究将评估维拉唑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，以鼓励研究参与和保留，并将提取基因组DNA，根据可能与维拉唑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. Preclinical and clinical studies implicate cannabinoid interactions with the serotonin system. Vilazodone, a compound combining serotonin reuptake inhibition and 5-HT1A partial agonism, has recently become available. Given its dual serotonergic mechanism of action, vilazodone may have promise as a treatment for marijuana dependence. Therefore, we propose to conduct a randomized, placebo-controlled trial of vilazodone in marijuana-dependent adults. A contingency management intervention coupled with motivational enhancement therapy will be incorporated to encourage study engagement and retention. Further, genomic DNA will be extracted to characterize subjects according to polymorphisms of genes relevant to the 5-HT1A receptor activity, specifically the C-(1019) G variant. We hypothesize that individuals who receive vilazodone 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 vilazodone, 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. Results from this study could lead to the development of a new pharmacotherapy for marijuana dependence and increase our knowledge of a potential genetic biomarker for prediction of outcomes. . 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 vilazodone 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, and genomic DNA will be extracted to characterize subjects according to polymorphisms of genes potentially relevant to the activity of vilazodone.