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898，000人长期使用海洛因，3，497，000人非医疗使用止痛药。对于接受治疗的人来说，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类药物依赖治疗方法。2000年的《药物成瘾治疗法》允许医生在办公室环境中开具FDA批准用于治疗阿片类药物依赖的III-V类药物。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低的药物，需要在办公室环境中使用。一种候选药物是曲马多，一种非典型阿片类药物。曲马多是一种有效的镇痛药，在μ阿片受体上发挥激动剂作用，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，在用于镇痛目的的常用剂量范围内是安全的。有轶事证据表明，曲马多可以成功地用于非复杂的阿片类药物戒断治疗，尽管没有系统的研究测试曲马多用于阿片类药物戒断或维持治疗。这项拨款建议进行一系列的人体实验室研究，检查曲马多的药理学特性。这些研究的总体目标是双重的：提供曲马多的药理学作用的详细表征，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类药物依赖的潜在价值。具体而言，将解决以下问题：1）不同剂量的曲马多抑制自发性阿片类戒断症状的相对疗效是什么，以及这如何作为不同程度的身体依赖的函数而变化？2)维持每日剂量的曲马多产生的身体依赖性水平是多少？3)不同维持剂量的曲马多在阻断μ受体激动剂阿片类药物作用方面的效果如何？4)在鉴别程序中，曲马多的药理学特征与其他药物相比如何？5)与可乐定和丁丙诺啡相比，当一个人用曲马多逐渐减少阿片类药物时，症状的严重程度和时间过程是什么？这些曲马多的研究将提供该药物在人体中的重要药理学特征，并为其作为可用于阿片类药物依赖的基于办公室的治疗的药物疗法的潜在用途提供基础。

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.