Tiagabine and Disulfiram for Cocaine Dependence

美沙酮维持患者中的共病可卡因依赖干扰了治疗结果。 双硫兰(DPH抑制剂)和替加宾(GAT-1阻滞剂)在治疗糖尿病方面显示出有希望的结果。 可卡因依赖。而抑制DPH活性被假设为增加了多巴胺 神经传递主要是在新皮质，为了加强使用可卡因的焦虑感， 假设选择性抑制GABA重摄取主要是为了减弱多巴胺的神经传递。 伏隔核和减少可卡因的强化作用。这项提议的目标是 为了确定对多巴胺β功能多态进行前瞻性筛查的程度 羟基酶(DBH-1021CDT)预测双硫仑和替加他滨治疗初治乳腺癌的疗效 接受美沙酮治疗的患者。DBH-1021CDT通过影响DBH调节血浆D0H水平 基因表达。根据我们的初步研究，我们假设低DPH相关T等位基因的携带者 将显著减少可卡因的使用，因为他们更容易受到D0Hby的抑制 双硫仑。相比之下，携带高DPH相关C等位基因的人在可卡因使用方面几乎没有减少 使用双硫兰，但由于替加宾的对比作用，与替加宾相比可能有显著的减少 减少多巴胺的释放。这项为期14周的双盲、安慰剂对照随机临床试验将 为150名可卡因依赖阿片依赖患者提供治疗。参赛者年龄介乎18至65岁， 随机接受双硫兰250毫克/天、替加他滨24毫克/天或安慰剂，同时接受 用美沙酮治疗。所有参与者每周接受1小时的心理治疗(认知行为 治疗)。根据自我报告的评估，主要成果将是减少阿片类药物和可卡因的使用 并通过每周三次的尿检确认。预计拟议的研究将提供更好的 了解DPH抑制剂双硫兰和选择性GABA重摄取抑制剂替加宾的作用 不同DBH-1021CDT基因型可卡因使用行为的研究

Comorbid cocaine dependence among methadone maintained patients interferes with treatment outcomes. Disulfiram (DPH inhibitor) and Tiagabine (GAT-1 blocker) have shown promising results in the treatment of cocaine dependence. While inhibition of DpH activity is hypothesized to increase dopamine neurotransmission primarily in the neocortexand to intensify the dysphoric experience of cocaine use, the selective inhibition of GABA reuptake is hypothesized to attenuate dopamine neurotransmission primarily in the nucleus accumbens and to reduce the reinforcing effects of cocaine use. The objective of this proposal is to determine to what extend does prospective screening for a functional polymorphism of dopamine beta hydroxylase (DBH-1021CDT) predict the treatment efficacy of disulfiram and tiagabine among newly admitted methadone treated patients. DBH-1021CDT regulates plasma D0H levels by influencing DBH gene expression. Based on our pilot studies, we hypothesize that carriers of the low-DpH associated T allele will have significant reductions in cocaine use, because they are more susceptible to inhibition of D0Hby disulfiram. In contrast, carriers of the high-DpH associatedC allele will have little reduction in cocaine use with disulfiram, but may have significant reductions with tiagabine, because of tiagabine's contrasting action in reducing dopamine release. This 14-week double-blind, placebo controlled randomized clinical trial will provide treatment for 150 cocaine-dependent opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive disulfiram 250mg/day,tiagabine 24mg/day, or placebo while concurrently receiving treatment with methadone. All participants receive weekly 1-hour psychotherapy(Cognitive Behavioral Treatment). The primary outcomes will be reduction in opioid and cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalyses. The proposed study is expectedto provide a better understanding of the role of the DpH inhibitor disulfiram and the selective GABA reuptake inhibitor tiagabine on cocaine using behavior among distinct DBH-1021CDT genotypes.