Evidence from clinical observation and randomized, placebo-controlled trials suggests that Cannabis sativa and its principal active constituent ?9-THC, may be effective in reducing tic severity. Strong preclinical evidence suggests endocannabinoids are important in the modulation of dopaminergic motor circuits. Fatty Acid Amide Hydrolase (FAAH)-inhibitors inhibit the degradation of endocannabinoids, one of the naturally occurring neurotransmitters that bind to brain cannabinoid receptors in the body. FAAH-inhibitors potentiate signaling without the psychoactive effects or the abuse liability of cannabis derivatives. FAAH-inhibitors have been safely used without significant side-effects in Phase IIA trial of adults with osteoarthritis of the knee. We will conduct a 12-week, placebo-controlled, crossover trial with two 4-week treatment phases separated by a 4-week washout period. Subjects will receive the FAAH-inhibitor or placebo in random order during each of the treatment phases. Our goal for this pilot study is to (1) provide initial safety, feasibility and tolerability data on a FAAH-inhibitor in a TS population and (2) provide data in order to make a more informed decision regarding the appropriate sample size and design of a larger clinical trial to prove efficacy. Michael H. Bloch, M.D., MS, Christopher Pittenger, M.D., Ph.D., James F. Leckman, M.D., and Deepak C. D’Souza, MBBS, M.D. Yale University Child Study Center and Department of Psychiatry, New Haven, CT Award: $74,985 Tourette Association of America Inc. – Research Grant Award 2014-2015