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.
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.
|Lile, Joshua A; Wesley, Michael J; Kelly, Thomas H et al. (2016) Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol. Behav Pharmacol 27:215-24|
|Lile, Joshua A; Stoops, William W; Rush, Craig R et al. (2016) Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans. Drug Alcohol Depend 165:111-9|
|Bolin, B Levi; Lile, Joshua A; Marks, Katherine R et al. (2016) Buspirone reduces sexual risk-taking intent but not cocaine self-administration. Exp Clin Psychopharmacol 24:162-73|
|Wesley, Michael J; Lile, Joshua A; Hanlon, Colleen A et al. (2016) Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation. Psychopharmacology (Berl) 233:1035-44|
|Johnson, Amy R; Banks, Matthew L; Blough, Bruce E et al. (2016) Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys. Drug Alcohol Depend 165:103-10|
|Marks, Katherine R; Lile, Joshua A; Stoops, William W et al. (2016) Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine. J Clin Psychopharmacol 36:213-21|
|Harvanko, Arit; Martin, Catherine; Lile, Joshua et al. (2016) Individual differences in the reinforcing and subjective effects of d-amphetamine: Dimensions of impulsivity. Exp Clin Psychopharmacol 24:436-446|
|Bolin, B Levi; Alcorn, Joseph L; Reynolds, Anna R et al. (2016) Human drug discrimination: A primer and methodological review. Exp Clin Psychopharmacol 24:214-28|
|Martin, Catherine Anne; Lile, Joshua; Guenthner, Greg et al. (2014) Behavioral effects of modafinil and nicotine, alone and in combination, in tobacco-deprived young adult smokers. J Clin Psychopharmacol 34:278-81|
|Marks, Katherine R; Lile, Joshua A; Stoops, William W et al. (2014) Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users. Psychopharmacology (Berl) 231:2741-50|
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