Buspirone Treatment for Marijuana Dependence

丁螺环酮治疗大麻依赖

• 批准号: 7687222
• 负责人: AIMEE L MCRAE-CLARK
• 金额: $ 32.84万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687222
• 关键词: Adult; Agonist; Basic Science; Biological Assay; Biological Markers; Buspirone; Cannabinoids; Cannabis; Chronic; Clinical Treatment; Clinical Trials; Combined Modality Therapy; Controlled Clinical Trials; Coupled; DNA; Data; Development; Disease; Double-Blind Method; Down-Regulation; Evaluation; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Health; Illicit Drugs; Individual; Intervention; Investigation; Knowledge; Lead; Marijuana; Marijuana Dependence; Marijuana Smoking; Measures; Methodology; Monitor; Outcome; Outcome Measure; Pharmaceutical Preparations; Pharmacogenetics; Pharmacological Treatment; Pharmacotherapy; Placebos; Population; Preclinical Drug Evaluation; Randomized Controlled Clinical Trials; Research; Research Design; Riboflavin; Rodent; Role; Screening Result; Serotonin; Serotonin Receptor 5-HT1A; Serum; Therapeutic Agents; Treatment outcome; United States; United States Substance Abuse and Mental Health Services Administration; Urine; Variant; contingency management; improved; medication compliance; motivational enhancement therapy; pill; preclinical study; public health relevance; randomized placebo controlled trial; receptor; response; treatment response

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.

描述（由申请人提供）：大麻是美国最常用的非法药物。尽管大麻素的使用和潜在的健康后果广泛存在，而且对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-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，我们建议在大麻依赖个体中进行丁螺环酮的双盲随机试验。应急管理（CM）干预与动机增强疗法（MET）相结合，以鼓励学习投入和保留。我们假设接受丁螺环酮联合MET和CM治疗的个体与接受安慰剂联合MET和CM治疗的个体相比，大麻使用结果会有所改善。此外，由于5-HT1A受体的遗传变异已经被确定，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多态性来表征受试者。我们假设5-HT1A受体功能缺陷的个体比5-HT1A受体功能缺陷的个体治疗效果更差。最后，由于依从性的可靠评估对结果测量的解释至关重要，我们提出了第二个目标，即开发和验证丁螺环酮的主要代谢物（6-羟基丁螺环酮）的测定，以测量治疗的依从性。这项研究的结果可能会导致大麻依赖的新药物治疗的发展，增加我们对预测结果的潜在遗传生物标志物的认识，并改进大麻依赖调查的临床试验方法。