Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders

描述（由申请人提供）：有很大的需要提高治疗阿片类药物使用障碍（OUD）的药物的有效性，另外还有相当大的需要开发治疗大麻使用障碍（CUD）的有效药物。本中心的新主题是根据药物改善大麻素和阿片类药物使用障碍（即戒断引起的戒断和复发）的临床后遗症的能力来检查药物，部分原因是它们具有共同的神经生物学基础。该中心由4个核心和4个项目组成，具有相当大的协同作用和相互依赖性。将所有项目统一为行政核心、研究核心、试点项目核心和培训教育核心。在该中心的前2.5年，项目2和项目4的二期临床试验将测试大麻素/阿片类药物联合纳比龙和纳曲酮治疗CUD和OUD的联合策略。同时，项目1和项目3的人体实验室研究将使用先验决策算法评估药物（氯卡色林、大麻二酚、doxazosin和zonisamide，可能与纳比龙或丁丙诺啡或缓释纳曲酮联合使用），以确定候选药物，以便在项目2和项目4的后续II期临床试验中进行测试。该中心有明确的组织结构，并将以具有成本效益的方式开展工作。研究团队可获得的资源，以及机构的支持，确保了中心目标的成功实现。这些措施包括：1)使用有效的决策算法在实验室中单独或联合测试药物，并将那些显示“积极”信号的药物迅速转移到临床；2)在II期对照试验中测试这些来自实验室的“阳性”药物的疗效；3)探索实验室和临床环境中药物效果的预测因素；4)培训初级调查员成为下一代药物滥用的领导者；5)在本地、国内和国际上传播循证研究成果。该申请建立在我们研究团队的优势和成就的基础上，同时在大麻素和阿片类药物的共享药物开发方面取得了创新进展。我们的创新方法将确保我们的中心是协同的，转化的，并在药物开发的前沿。总之，本中心非常注重使用最有效的方法来寻找潜在的药物制剂来治疗两种具有重大临床关注的疾病，即大麻和阿片类药物使用障碍。

DESCRIPTION (provided by applicant): There is substantial need for improving the effectiveness of medications for treating opioid use disorder (OUD), plus a considerable need to develop effective medications for cannabis use disorder (CUD). The novel overarching theme of this Center is to examine medications based on their ability to improve clinical sequelae common to both cannabinoid and opioid use disorders (i.e., abstinence-induced withdrawal and relapse), in part due to their shared common neurobiologic underpinnings. This Center consists of 4 Cores and 4 Projects with considerable synergy and interdependency. Unifying all of the Projects are the Administrative Core, the Research Core, the Pilot Project Core, and the Training and Education Core. In the first 2.5 years of this Center, Phase II clinical trials in Project 2 and Project 4 will test the combined cannabinoid/opioid strategy of combining nabilone and naltrexone for both CUD and OUD. Meanwhile, the human laboratory studies in Project 1 and Project 3 will evaluate medications (lorcaserin, cannabidiol, doxazosin, and zonisamide, potentially in combination with nabilone or buprenorphine or sustained-release naltrexone) using a priori decision algorithms to identify candidate medications to be tested in subsequent Phase II clinical trials in Projects 2 and 4. The Center has a clear organizational structure and will b conducted in a cost-efficient manner. The resources available to the research team, along with the institutional support, ensure the success in attaining the Aims of the Center. These include: 1) Use of efficient decision algorithms to test medications alone, and in combination, in the laboratory and move those that show a "positive" signal rapidly into the clinic; 2) Test these "positive" medications from the laboratory for efficacy in Phase II controlled trials; 3) Explore predictors of medication effects in the laboratory and clinic settings; 4) Train junior investigatos to become the next generation of leaders in substance abuse; and 5) Disseminate evidence-based research findings locally, nationally and internationally. This application builds on the strengths and achievements of our research team, while developing innovative advances in shared medications development for cannabinoids and opioids. Our innovative approach will ensure that our Center is synergistic, translational and at the cutting edge of medications development. In sum, this Center is strongly focused on using the most efficient approach to find potential pharmacologic agents to treat two disorders that are of great clinical concern, namely, cannabis and opioid use disorders.