Disulfiram for Cocaine Abuse in Methadone- Patients

描述：(申请人摘要) 因为可卡因的使用在大多数阿片类药物维持方案中仍然很普遍， 针对可卡因的药物治疗策略 多巴胺能作用在未经选择的人群中几乎没有显示出效果，这 提案将研究一种治疗可卡因的新药理策略 阿片类药物维持的可卡因滥用者的滥用情况；即使用双硫仑治疗。 具体地说，这项建议的目的是检查双硫兰的效果。 (0、62.5、125或250 mg/天)对美沙酮维持治疗结果的影响 可卡因滥用者。这项为期14周的双盲随机临床试验将 为160名阿片类药物和可卡因依赖者(18-65岁)提供治疗 年)。参与者将在1-2周内接受美沙酮维持治疗， 届时将评估可卡因的使用水平。然后参与者将继续 在美沙酮维持方面，并被随机分配到接受 以下剂量的双硫兰：0、62.5、125或250毫克/天。在.期间 美沙酮稳定(第1-2周)，参与者通常被给予 每天增加美沙酮的剂量，直到维持剂量达到 达到了。然后，在治疗阶段(5-14周)，参与者继续 接受他们每天维持剂量的美沙酮。此外，他们还 每日服用双硫仑/安慰剂。在研究结束时，参与者 将在四周内接受美沙酮的戒毒治疗。为了 改善结果，所有参与者每周接受1小时的心理治疗 (认知行为治疗)与经验丰富的临床医生特别 接受了提供治疗的培训，并将接受持续监督。这个 主要成果将是保留和减少阿片类药物和可卡因的使用，如 通过自我报告进行评估，并通过每周三次的尿检确认。次要的 成果还将包括减少其他非法药物和酒精的使用。 心理社会功能的改善。与预后的相关性 多巴胺β-羟基酶基因座的基因分型 还将检查酶活性和可卡因依赖的严重程度。

DESCRIPTION: (Applicant's Abstract) Because cocaine use remains epidemic among most opioid maintenance programs and pharmacological therapeutic strategies specifically aimed at cocaine's dopaminergic actions have shown little efficacy in unselected populations, this proposal will examine a novel pharmacological strategy for treating cocaine abuse in opioid-maintained cocaine abusers; i.e., treatment with disulfiram. Specifically, the aim of this proposal is to examine the effects of disulfiram (0, 62.5, 125, or 250mg /day) on treatment outcome in methadone-maintained cocaine abusers. This 14-wk, double blind, randomized clinical trial will provide treatment for 160 opioid- and cocaine-dependent individuals (18-65 years). Participants will be placed on methadone maintenance during weeks 1-2, at which time level of cocaine use is assessed. Then participants will continue on methadone maintenance and be randomly assigned to receive one of the following doses of disulfiram: 0, 62.5, 125, or 250 mg/day. During stabilization on methadone (wks 1-2), participants typically are administered increasing doses of methadone on a daily basis until maintenance doses are attained. Then during the treatment phase (weeks 5-14), participants continue to receive their daily maintenance doses of methadone. In addition, they receive disulfiram/placebo on a daily basis. At the end the study, participants will undergo detoxification from methadone over a 4-week period. In order to enhance outcome, all participants receive weekly 1-hour psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be retention and reduction in opioid and cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalyses. Secondary outcomes will include reductions in other illicit drug and alcohol use, as well as improvements in psychosocial functioning. The prognostic relevance of genotype at the dopamine beta-hydroxylase locus, dopamine beta-hydroxylase enzyme activity, and severity of cocaine dependence will also be examined.