Tiagabine for Cocaine Dependence in Methadone Treatment

描述（由申请人提供）：尚未开发出有效的可卡因依赖药物治疗。美沙酮维持治疗患者中共病可卡因依赖干扰治疗结果，并增加静脉使用复发的风险，这与艾滋病毒和丙型肝炎风险增加有关。增强的GABA神经传递似乎减弱了可卡因的强化作用。本建议的目的是研究在何种程度上增强GABA系统会改变可卡因使用行为，并减轻新入院的美沙酮治疗患者的阿片类药物戒断症状。主要的假设是，增强GABA系统与GABA转运体阻断剂噻加宾，我们希望减少可卡因的使用，并促进戒毒可卡因滥用美沙酮治疗的患者。第二个假设是，增强GABA系统与GABA转运体阻断剂噻加宾，我们希望在新入院的美沙酮治疗的患者减轻早期阿片类药物戒断症状。这些假设是根据我们的试点研究，使用选择性GABA再摄取抑制剂噻加宾制定的。 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岁之间的参与者将随机接受噻加滨32 mg/天、噻加滨20 mg/天或安慰剂，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（认知行为疗法），由经验丰富的临床医生专门培训提供治疗，并接受持续的监督。 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，通过自我报告和每周三次尿分析进行评估。该研究有望更好地了解选择性GABA再摄取抑制剂噻加宾对可卡因使用行为和阿片类药物戒断症状治疗的作用，并将为开发美沙酮治疗患者中共病可卡因依赖的新药物干预提供有价值的信息。

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.