Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders

说明(申请人提供)：有相当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，以及相当需要开发有效的大麻使用障碍药物(CUD)。该中心的新的总体主题是审查药物是否有能力改善大麻素和阿片类药物使用障碍(即戒断诱导的戒断和复发)常见的临床后遗症，部分原因是它们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存关系。将所有项目统一为行政核心、研究核心、试验项目核心和培训和教育核心。在该中心的头两年半时间里，项目2和项目4的第二阶段临床试验将测试将纳比隆和纳曲酮联合用于CUD和OUD的大麻素/阿片类药物组合策略。与此同时，项目1和项目3中的人体实验室研究将使用先验决策算法来评估药物(氯卡瑟林、大麻二醇、多沙唑嗪和唑尼沙胺，可能与纳贝酮、丁丙诺啡或缓释纳曲酮联合使用)，以确定将在项目2和项目4的后续第二阶段临床试验中测试的候选药物。该中心有一个明确的组织结构，并将以具有成本效益的方式进行。为研究小组提供的资源，加上机构支持，确保成功地实现中心的目标。这些措施包括：1)使用有效的决策算法在实验室单独和联合测试药物，并将那些显示“阳性”信号的药物迅速转移到临床；2)在第二阶段对照试验中测试这些来自实验室的“阳性”药物的有效性；3)在实验室和临床环境中探索药物效果的预测因素；4)培训初级研究人员，使其成为药物滥用领域的下一代领导者；以及5)在地方、国家和国际传播循证研究结果。这项应用建立在我们研究团队的优势和成就的基础上，同时在大麻类和阿片类药物的共享药物开发方面取得创新进展。我们的创新方法将确保我们的中心具有协同性、转化性，并处于药物开发的前沿。总而言之，该中心致力于使用最有效的方法寻找潜在的药理药物来治疗两种临床上非常令人担忧的疾病，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.