Genetic variation in fatty acid amide hydrolase (FAAH): Associations with early drinking and smoking behaviors

Background: The endocannabinoid system is implicated in psychiatric disorders and drug dependence. Within this system, fatty acid amide hydrolase (FAAH) metabolizes endocannabinoids. Individuals with A-group genotypes (C/A or A/A) of a common FAAH variant (rs324420; C > A; Pro129Thr) have slower enzymatic activity compared to C-group individuals (C/C genotype). Slow FAAH activity is differentially associated with alcohol and nicotine use. Methods: Among European-ancestry participants in the NDIT study (n = 249-607), genotype associations with past-year binge drinking in young adults were estimated in logistic regression models. In adolescents, hazard ratios (HR) were estimated from Cox proportional hazards models to assess the FAAH genotype group association with time to drinking initiation and attaining drinking frequency outcomes. HR were also used to assess genotype effect on time to smoking initiation and attaining early smoking milestones (e.g., first inhalation, ICD-10 dependence). Results: Compared to those in the C-group, those in the A-group had higher odds of binge drinking at ages 20 (Odds ratio (OR) = 2.16, 95 % CI 1.36-3.42) and 30 (OR = 1.61, 95 % CI 1.10-2.36). Time to initiation of drinking and daily drinking was faster in adolescents in the A-group (HR = 1.39, 95 % CI 1.09-1.77 and HR = 2.24, 95 % CI 1.05-4.76, respectively). Time to smoking initiation was faster in the A-group (HR = 1.20, 95 % CI 1.04-1.39); however, time to smoking milestones among adolescent smokers was not consistently different for the A-versus C-groups (HR = 0.43 to 1.13). Conclusions: Slow FAAH activity (A-group) was associated with greater risks for binge drinking, drinking initi-ation and escalation, and cigarette smoking initiation, but had little impact on the escalation in cigarette smoking behaviors.