Fatty acid amide hydrolase (FAAH) has also been studied in relation to acute response to stimulants; FAAH degrades several endocannabinoids that bind to cannabinoid receptors (McKinney and Cravatt 2005). Recently, polymorphisms in FAAH have been associated with brain response to cannabis (Filbey et al. 2009) and other phenotypes such as obesity (Engeli 2008). Much of the work associating variants in FAAH with stimulant response has been done in animal models (e.g., Madsen et al. 2006), and has shown that response to stimulants may also be influenced by the cannabinoid system. We investigated the effect of FAAH polymorphisms on subjective responses to acute amphetamine, using the sample of healthy volunteers that has been previously described (Dlugos et al. 2009b). Two SNPs, rs3766246 (C/C genotype) and rs2295633 (C/C genotype), were associated with amphetamine-induced arousal and decreased fatigue at 10 mg but not 20 mg, supporting the hypothesis that the endocannabinoid system may influence the acute response to low doses of amphetamine.
