One candidate gene of interest for CD is FAAH (alias FAAH-1). FAAH encodes for fatty acid amide hydrolase (FAAH), an enzyme expressed in the brain and liver that inactivates N-arachidonoyl–ethanolamine (anandamide), an endogenous agonist for CB1 cannabinoid receptors (Cravatt and Lichtman 2003). Delta-9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in marijuana, is also a CB1 agonist. CB1 binding increases dopamine transmission along mesocorticolimbic pathways (Gessa et al. 1998; Mascia et al. 1999), the activation of which underlies many facets of addiction (e.g., Robinson and Berridge 1993). Decreases in FAAH efficacy may increase sensitivity to anandamide (Cravatt et al. 2001), and thereby alter mesocorticolimbic dopaminergic activity. Alterations in endocannabinoid signaling have been associated with a variety of SUD phenotypes in animal models (Wiskerke et al. 2008).
