Medications Development for Cannabis-Use Disorders: Clinical Studies

描述（由申请人提供）：大麻是美国最常用的非法药物，其使用与滥用和依赖的发展率、治疗入院率和复发率有关，与其他非法药物相当。目前还没有有效的药物治疗大麻使用障碍。我职业生涯的首要目标是开发一个临床研究项目，在该项目中，我能够使用有效的、以证据为基础的实验室程序进展来筛选大麻使用障碍的潜在药物，然后评估有希望的药物在依赖性、寻求治疗的个体中的疗效。我的研究生和博士后培训以及K 01和R 01的支持使我能够建立一个独立的研究计划，其中药物开发的合理目标是根据9-THC的神经药理学确定的。我的研究已经确定了可能代表大麻使用治疗重大突破的化合物。这个K 02奖的目标是继续我的职业发展轨迹，通过获得额外的技能和经验，需要移动到筛选过程的下一步我的研究。为了实现这一目标，我制定了一个职业发展计划，其中包括额外的课程，与专家导师的培训，相关的研究和数据出版/介绍活动，进一步发展赠款，以及接受和提供负责任的研究培训。在资助期间进行的研究包括三个步骤的筛选过程，以1）确定随后筛选的目标和/或特定化合物; 2）测试候选药物维持期间大麻给药的安全性和耐受性;和3）测试在受控实验室条件下维持假定药物疗法以减弱大麻的强化作用的能力，同时监测自然生态中大麻使用的变化。重要的是，这最后一步代表了一种创新的方法，将提高早期临床试验研究的效率，指导候选药物的选择，以进行全面的临床疗效测试，并促进我最终过渡到临床试验研究。这项研究将在肯塔基州大学行为科学系进行，这是一个特殊的环境，具有成功完成拟议的职业发展计划所需的物质和智力资源。此外，该机构致力于我的科学发展，并承认我的研究计划是其科学界不可分割的一部分。我有培训和研究经验的坚实基础，建立了生产力和独立资金的良好记录，并表现出对指导下一代对大麻使用障碍治疗感兴趣的学者的承诺。K 02奖支持的职业发展活动将使我能够维持和扩大这些努力，从而实现我的职业目标，这将直接影响大麻使用治疗领域。 公共卫生相关性：大麻是美国最常用的非法药物，其使用与滥用和依赖的形成率、接受治疗率和复吸率有关，与其他非法药物相当。目前还没有有效的药物治疗大麻使用障碍。五年的资金要求支持全职（100%的努力）研究和培训，以支持开发一个有效的循证药物筛选过程。

DESCRIPTION (provided by applicant): Cannabis is the most commonly used illicit drug in the United States, and its use is associated with rates of development of abuse and dependence, treatment admission and relapse that are comparable to other illicit drugs. Currently there is no effective pharmacological treatment for cannabis-use disorders. The overarching goal of my career is to develop a clinical research program in which I am able to screen potential medications for cannabis-use disorders using an efficient, evidence-based progression of laboratory procedures followed by an evaluation of the efficacy of promising leads in dependent, treatment-seeking individuals. My graduate and post-doctoral training and K01 and R01 support have enabled me to build an independent research program in which rational targets for medications development are identified based on the neuropharmacology of 9-THC. My research has identified compounds that could represent major breakthroughs in cannabis-use treatment. The goal of this K02 award is to continue my career development trajectory by acquiring the additional skills and experience needed to move my research into the next steps of the screening process. In order to achieve this goal, I have formulated a career development plan that includes additional coursework, training with expert preceptors, relevant research and data publication/presentation activities, further grant development, and the receipt and delivery of training in the responsible conduct of research. The research to be conducted during the funding period consists of a three-step screening process to 1) identify targets and/or specific compounds for subsequent screening; 2) test the safety and tolerability of cannabis administration during maintenance on candidate medications; and 3) test the ability of maintenance on putative pharmacotherapies to attenuate the reinforcing effects of cannabis under controlled laboratory conditions while simultaneously monitoring changes in cannabis use in the natural ecology. Importantly, this last step represents an innovative approach that will enhance the efficiency of early phase clinical trial research, direct the choice of candidate medications for full scale clinical efficacy testing, and facilitate my eventual transition to clinical trials research. This research will be carried out in the Department of Behavioral Science at the University of Kentucky, which is an exceptional environment, having the necessary physical and intellectual resources for successful completion of the proposed career development plan. Moreover, this institution is committed to my scientific development and has acknowledged that my research program is an integral part of its scientific community. I have a solid foundation of training and research experience, have established a strong record of productivity and independent funding, and have demonstrated a commitment to mentoring the next generation of scholars interested in the treatment of cannabis-use disorders. The career development activities supported by the K02 award will allow me to sustain and expand these efforts, and thus meet my career goals, which will directly impact the field of cannabis-use treatment. PUBLIC HEALTH RELEVANCE: Cannabis is the most commonly used illicit drug in the United States, and its use is associated with rates of development of abuse and dependence, treatment admission and relapse that are comparable to other illicit drugs. Currently there is no effective pharmacological treatment for cannabis-use disorders. Five years of funding is requested to support full-time (100% effort) research and training to support the development of an efficient evidence-based medication screening process.