Medications Development for Drug Abuse Disorders

描述(由申请人提供)： 最近的联邦估计表明，在过去的一个月里，至少有89.8万人长期使用海洛因，349.7万人使用了非医疗止痛药。在接受治疗的人中，最常见的非法药物是海洛因(243,523人)，超过了可卡因和大麻(分别为218,311人和236,638人)。这表明需要继续开发新的阿片依赖治疗方法。2000年的《药物成瘾治疗法》允许医生开出FDA批准的附表III-V药物，用于治疗办公室环境中的阿片依赖。然而，目前批准的唯一药物是丁丙诺啡，其他药物疗法，特别是那些滥用可能性较低的药物疗法，需要在办公室环境中使用。一种候选药物是曲马多，一种非典型的阿片类药物。曲马多是一种有效的止痛药，在u阿片受体上发挥兴奋作用，但似乎具有较低的滥用潜力。曲马多具有良好的口服生物利用度，在通常用于止痛的剂量范围内是安全的。有坊间证据表明，曲马多可以成功地用于非复杂的阿片类药物戒断治疗，尽管没有系统研究测试曲马多用于阿片类药物戒断或维持治疗。这笔赠款建议进行一系列人体实验室研究，检查曲马多的药理特性。这些研究的总体目标有两个：仔细描述曲马多的药理学效应，并确定这种药物作为一种新的药物在办公室环境中治疗阿片依赖的潜在价值。具体地说，将讨论以下问题：1)不同剂量的曲马多对抑制自发阿片类药物戒断症状的相对有效性是什么，以及这种相对有效性是如何随着身体依赖程度的不同而变化的？2)每天维持曲马多剂量所产生的身体依赖程度如何？3)不同维持剂量的曲马多在阻断MU激动剂阿片类药物的作用方面有多有效？4)在辨别程序中，曲马多与其他药物相比，曲马多的药理学特征如何？5)与可乐定和丁丙诺啡相比，当一个人逐渐停用阿片类药物时，症状的严重程度和时间进程如何？这些对曲马多的研究将为这种药物在人类中的应用提供重要的药理学特征，并为其作为一种可用于办公室阿片依赖治疗的药物疗法提供基础。

DESCRIPTION (provided by applicant): Recent federal estimates indicate there are at least 898,000 chronic users of heroin and 3,497,000 persons have had nonmedical use of a pain reliever in the past month. For persons entering treatment, the most common illicit drug used is heroin (243,523 persons) - surpassing both cocaine and marijuana (218,311 and 236,638, respectively). This suggests the need for continued development of new opioid dependence treatments. The Drug Addiction Treatment Act of 2000 allows physicians to prescribe schedule III-V medications that are FDA approved for the treatment of opioid dependence in office settings. However, the only medication currently approved is buprenorphine, and other pharmacotherapies, and especially those with low abuse potential, are needed for use in office-based settings. One candidate medication is tramadol, an atypical opioid. Tramadol is an effective analgesic that exerts agonist effects at the mu opioid receptor, but appears to have a low abuse potential. Tramadol has good oral bioavailability and is safe in the usual dose range used for analgesic purposes. There is anecdotal evidence that tramadol can be successfully used for non-complicated opioid withdrawal treatment, although there are no systematic studies testing tramadol when used for either opioid withdrawal or maintenance treatment. This grant proposes to conduct a series of human laboratory studies examining the pharmacological characteristics of tramadol. The overall goals of these studies are two-fold: to provide a careful characterization of tramadol's pharmacological profile of effects, and to determine this medication's potential value as a new agent for the treatment of opioid dependence in office-based settings. Specifically, the following questions will be addressed: 1) What is the relative efficacy of different doses of tramadol for suppressing symptoms of spontaneous opioid withdrawal, and how does this vary as a function of different levels of physical dependence? 2) What is the level of physical dependence produced by maintenance on daily doses of tramadol? 3) How effective are different maintenance doses of tramadol in blocking the effects of mu agonist opioids? 4) How do the pharmacological characteristics of tramadol compare to other drugs in a discrimination procedure? 5) What is the severity and time course of symptoms that occur when a person is tapered off opioids with tramadol, compared to a clonidine and buprenorphine? These studies of tramadol will provide an important pharmacological characterization of this medication's profile in humans, and also provide a foundation for its potential use as a pharmacotherapy that can be utilized in the office-based treatment of opioid dependence.