Residing on human chromosome 1p35−34, the FAAH gene is 19.5kb in length and includes 15 exons. The gene is widely expressed in the central nervous system. There is evidence that while progesterone and leptin upregulate [62] the 674 bp FAAH promoter, estrogen and glucocorticoids [63] downregulate its activity. To date, there have been 4 association studies of FAAH and substance use disorders. A majority of these studies tested the effects of a missense mutation (C385A) that converts a conserved proline residue to threonine in exon 3 (rs324420, previously rs57947754). There is considerable evidence that this missense mutation is associated with risk for substance dependence (Table 3) in Caucasian and African-American, but not in Japanese or other Asian populations [64-66]. Sipe and colleagues [67,66] characterized this polymorphism and found that individuals homozygous for the minor A allele, were nearly 5 times more likely to be street drug users or to report problems with alcohol or drugs. The effects were strongest in those with comorbid drug and alcohol problems but there were no statistically significant effects in individuals with alcohol or nicotine
