FAAH knockout mice [FAAH (−/−)] display exaggerated responses to anandamide, suggesting that FAAH is the primary regulator of anandamide signaling (Cravatt et al. 2001). Although no common human mutation causes FAAH deletion, a missense single nucleotide polymorphism (SNP), C385A (rs324420), results in a mutant form of FAAH with reduced expression and cellular stability (Chiang et al. 2004). The A allele of this SNP has demonstrated association with street drug use, problem drug and alcohol use (Sipe et al. 2002), and multiple substance dependences (Flanagan et al. 2006). However, one group did not find any association with methamphetamine dependence (Morita et al. 2005), and the C allele has also been associated with increased risk for progression to CD, although this result has not yet been replicated (Tyndale et al. 2007). Our group has reported an association between the C allele and craving after marijuana abstinence (Haughey et al. 2008). To our knowledge, no other studies have examined FAAH C385A and intermediate phenotypes of CD.
