Association of the Fatty Acid Amide Hydrolase C385A Polymorphism with Alcohol Use Severity and Coping Motives in Heavy-drinking Youth

Background: Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether this inherited difference in endocannabinoid metabolism relates to alcohol use disorder etiology and patterns of alcohol use in youth is unknown. Methods: To examine this question, heavy-drinking youth (n = 302; mean age = 19.74 ± 1.18) were genotyped for FAAH C385A. All subjects completed a comprehensive interview assessing alcohol use patterns including the Timeline Follow-back Method, Alcohol Use Disorders Identification Test (AUDIT) and Drinking Motives Questionnaire. ANCOVAs were conducted to assess differences in drinking patterns and drinking motives between genotype groups, and mediation analyses investigated whether drinking motives accounted for indirect associations of genotype with alcohol use severity. Results: Youth with the FAAH minor allele (AC or AA genotype) reported significantly more frequent drinking days (p=0.045), significantly more frequent heavy episodic drinking (p=0.003) and significantly higher consumption patterns (AUDIT p=0.045, AUDIT-C p=0.02). Mediation analyses suggested that the association of FAAH C385A with drinking outcomes was mediated by coping motives. Conclusions: These findings extend previous studies by suggesting that reduced endocannabinoid metabolism may be related to heavier use of alcohol in youth, prior to the onset of chronic drinking problems. Furthermore, differences in negative reinforcement-related drinking might account in part for this association.