PHARMACOTHERAPY DOSING REGIMEN

可卡因依赖单独或与阿片类药物依赖并存都很难治疗。我们有 报告称，使用一种有效的激动剂，两个人群的可卡因使用量都有所减少。单一依赖的结果已经得到澳大利亚同事的证实。这项拟议的工作是根据先前的研究进行的。主题是为这些困难人群描绘具有代表性的药物、剂量和组合。第一年：我们将继续进行Small N的初步评估，以进一步评估剂量参数。这些药物将包括d-苯丙胺和莫达非尼、美沙酮和莫达非尼以及美沙酮和阿立哌唑的组合。第二至第五年：我们将进行大型随机对照试验，并继续进行相关的小型试验。研究一将包括200名自愿使用的可卡因，受试者分布在4组：1)30毫克d-苯丙胺+200毫克(估计)莫达非尼；2)200毫克(估计)莫达非尼；3)400毫克(估计)莫达非尼；4)安慰剂。第二项研究将包括200名自愿接受可卡因+阿片类药物依赖的受试者，这些受试者分布在5组，每天最多服用1.2毫克/公斤美沙酮。分组为：1)200毫克莫达非尼；2)400毫克莫达非尼；3)5毫克阿立哌唑；4)10毫克阿立哌唑；5)安慰剂。在同意后，受试者将进行全面的医疗和精神评估，每周进行三次尿检，每周进行基于认知行为/复发预防的治疗，并使用标准测量电池进行定期监测。此外，根据项目2，所有同意的受试者在研究开始和结束时都将进行功能磁共振成像。

Cocaine dependence alone or co-occurring with opioid dependence is difficult to treat. We have reported reduced cocaine use in both populations using a potent agonist. Single dependence results have been confirmed by Australian colleagues. The proposed work follows from earlier studies. The theme is delineation of representative medications, doses and combinations for these difficult populations. Year I: We will continue preliminary small N evaluations to further evaluate dosing parameters. These will include combinations of d-amphetamine and modafinil, methadone and modafinil, and methadone and aripiprazole. Years II-V: We will conduct large RCT's, with continuing related small trials. Study I will include 200 consenting cocaine using subjects distributed across 4 groups: 1) 30 mg d-amphetamine+ 200 mg (estimate) modafinil; 2) 200 mg (est) modafinil; 3) 400 mg (est) modafinil; 4) placebo. Study II will include 200 consenting cocaine+opioid dependent subjects distributed across 5 groups all receiving up to1.2 mg/kg methadone/day. Groups will be: 1) 200 mg (est) modafinil; 2) 400 mg (est) modafinil; 3) 5 mg (est) aripiprazole; 4) 10 mg (est) aripiprazole; 5) placebo. Following consent, subjects will have complete medical and psychiatric evaluations, provide thrice weekly urine screens, weekly cognitive behavioral / relapse prevention based therapy, and regular monitoring with a standard measurement battery. Also, per Project 2, all consenting subjects will have fMRI at study entry and end.