Vilazodone 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。临床前和临床研究表明大麻素与5-羟色胺系统相互作用。维拉唑酮，一种结合5-羟色胺再摄取抑制和5-HT 1A部分激动作用的化合物，最近已经上市。鉴于其双重的大麻能作用机制，维拉唑酮可能有希望作为大麻依赖的治疗。因此，我们建议在大麻依赖的成年人中进行一项随机、安慰剂对照的维拉唑酮试验。将纳入应急管理干预与动机增强治疗，以鼓励参与和保留研究。此外，将提取基因组DNA以根据与5-HT 1A受体活性相关的基因的多态性（特别是C-（1019）G变体）来表征受试者。我们假设，与接受安慰剂治疗结合MET和CM的个体相比，接受维拉唑酮治疗结合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，并可能改变对维拉唑酮的反应，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。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，并增加我们对预测结果的潜在遗传生物标志物的了解。.

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. .