Tiagabine for Cocaine Dependence in Methadone Treatment

描述(申请人提供)：目前还没有针对可卡因依赖的有效药物治疗方法。美沙酮维持患者对可卡因的共病依赖干扰了治疗结果，并增加了再次使用静脉注射的风险，这与艾滋病毒和丙型肝炎的风险增加有关。增强的GABA神经传递似乎减弱了可卡因的增强作用。这项提案的目的是检查增强GABA系统将在多大程度上改变新入院的美沙酮治疗患者的可卡因使用行为和减轻阿片类药物戒断症状。主要的假设是，用GABA转运体阻滞剂替加宾增强GABA系统，我们预计将减少可卡因的使用，并促进美沙酮治疗的可卡因滥用患者的戒断。第二个假设是，使用GABA转运体阻滞剂替加宾增强GABA系统，我们预计可以减轻新入院的美沙酮治疗患者的早期阿片类药物戒断症状。这些假说是基于我们使用选择性GABA再摄取抑制剂替加宾进行的初步研究提出的。 这项为期14周的双盲安慰剂对照随机临床试验将为120名可卡因和阿片类药物依赖患者提供治疗。年龄在18-65岁之间的参与者将被随机分成三组，分别接受替加宾32毫克/天、替加滨20毫克/天或安慰剂治疗，同时接受美沙酮治疗。所有参与者每周接受1小时的个人心理治疗(认知行为治疗)，有经验的临床医生接受专门培训来提供治疗，并将接受持续的监督。3个月的随访将使我们能够评估阿片类药物和可卡因的使用情况，以及心理社会适应的变化。主要结果将是戒断率和阿片类药物和可卡因使用的减少，这是通过自我报告和每周三次尿检来评估的。这项拟议的研究有望更好地了解选择性GABA再摄取抑制剂替加宾在可卡因使用行为和阿片类药物戒断症状治疗中的作用，并将为开发新的药物干预措施来治疗美沙酮治疗患者的共病可卡因依赖提供有价值的信息。

DESCRIPTION (provided by applicant): No effective pharmacological treatment for cocaine dependence has yet been developed. Comorbid cocaine dependence among methadone maintained patients interferes with treatment outcomes, and increases the risk of relapse to IV use, which is associated with increased risk for HIV and Hepatitis C. Enhanced GABA eurotransmission appears to attenuate cocaine's reinforcing effects. The objective of this proposal is to examine to what extend will enhancing the GABA system modify cocaine-using behavior and attenuate opiate withdrawal symptoms among newly admitted methadone treated patients. The primary hypothesis is that enhancing the GABA system with a GABA transporter blocker tiagabine we expect to reduce cocaine use and to promote abstinence in cocaine abusing methadone treated patients. The secondary hypothesis is that enhancing the GABA system with a GABA transporter blocker tiagabine we expect to attenuate early opiate withdrawal symptoms in newly admitted methadone treated patients. These hypotheses are formulated based on our pilot studies using the selective GABA re-uptake inhibitor tiagabine. This 14-week double-blind, placebo controlled randomized clinical trial will provide treatment for 120 cocaine and opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive tiagabine 32mg/day, tiagabine 20mg/day or placebo while concurrently receiving treatment with methadone. All participants receive weekly 1-hour individual psychotherapy (Cognitive Behavioral Therapy) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. A follow-up at 3 months will allow us to evaluate opioid and cocaine use, and changes in psychosocial adjustment. The primary outcomes will be abstinence rates and reduction in opioid and cocaine use, as assessed by self-report and thrice-weekly urinalyses. The proposed study is expected to provide a better understanding of the role of the selective GABA re-uptake inhibitor tiagabine on cocaine using behavior and treatment of opiate withdrawal symptoms, and will provide valuable information to develop new pharmacological interventions for comorbid cocaine dependence among methadone treated patients.