Methadone Studies

项目总结(见说明)： 美沙酮维持患者中的共病可卡因依赖干扰了治疗结果。 哌唑嗪(α-肾上腺素能拮抗剂)和DPH抑制药(双硫仑)在治疗可卡因依赖方面显示出良好的效果。而DPH活性的抑制被认为是增加了多巴胺(DA)，但减少了去甲肾上腺素的神经传递，并加剧了可卡因的焦虑感 α-肾上腺素能受体拮抗剂的选择性抑制被认为是为了减弱主要在伏核的DA神经传递，并减少可卡因的强化作用。 本研究的目的是确定在新入院的美沙酮治疗患者中，前瞻性筛查多巴胺β羟基酶功能多态(DBH-1021C？Vt)或α-α肾上腺素受体基因启动子区和编码区多态(ADRAIA)能在多大程度上预测奈匹卡司(一种新的DPH抑制剂)或哌唑嗪的疗效。根据我们以前的研究，我们假设低OPH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奈匹卡司他抑制DPH的影响。我们还将在非手术后评估ADRAIA的功能变体对哌唑嗪反应的影响。这12个人- 每周双盲、安慰剂对照随机临床试验将为150名可卡因依赖阿片类药物依赖患者提供治疗，这些患者接受2周的美沙酮诱导和4周的停药，总共18周。年龄在18-65岁之间的参与者将被随机接受哌唑嗪10毫克/天， 奈匹卡司120毫克/天，或安慰剂，同时接受美沙酮治疗。所有参与者每周接受1小时的心理治疗(认知行为治疗)。主要结果将是减少阿片类药物和可卡因的使用，这是通过自我报告评估的，并得到每周三次尿液分析的证实。 这项拟议的研究有望通过不同的DBH-1021C-+T基因型或ADRA1A启动子和编码区的功能变异，更好地了解DPH抑制剂奈匹卡司和选择性αA肾上腺素能受体拮抗剂哌唑嗪在可卡因中的作用。

PROJECT SUMMARY (See instructions): Comorbid cocaine dependence among methadone maintained patients interferes with treatment outcomes. Prazosin (alphai-adrenergic antagonist) and DpH inhibition (disulfiram) have shown promising results in the treatment of cocaine dependence. While inhibition of DpH activity is hypothesized to increase dopamine (DA) but decrease norepinephrine neurotransmission and to intensify the dysphoric experience of cocaine use, the selective inhibition of alphai-adrenergic receptor antagonist is hypothesized to attenuate DA 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-1021C¿vT) or polymorphisms in the promoter region and the coding region ofthe alpha-la-adrenoceptor receptor gene (ADRAIA) predict the treatment efficacy of nepicastat (a new DpH inhibitor) or prazosin among newly admitted methadone treated patients. Based on our previous studies, we hypothesize that carriers ofthe low-OpH associated T allele will have significant reductions in cocaine use, because they are more susceptible to inhibition of DpH by nepicastat. We also will assess post-hoc the impact of functional variants ofthe ADRAIA on the response to prazosin. This 12- week double-blind, placebo controlled randomized clinical trial will provide treatment for 150 cocainedependent opioid dependent patients who have 2-weeks of methadone induction and 4 week discontinuation for 18-weeks total. Participants, aged 18-65 years, will be randomized to receive prazosin 10 mg/day, nepicastat 120mg/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 expected to provide a better understanding ofthe role ofthe DpH inhibitor nepicastat and the selective alphaiA adrenergic receptor antagonist prazosin on cocaine using behavior among distinct DBH -1021C-+T genotypes or the functional variants in the promoter and coding region of ADRA1A.