Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy‐Drinking Youth

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2021-03, Vol.45 (3), p.507-517
• Main Authors: Best, Laura M., Wardell, Jeffrey D., Tyndale, Rachel F., McPhee, Matthew D., Le Foll, Bernard, Kish, Stephen J., Boileau, Isabelle, Hendershot, Christian S.
• Format: Article
• Language: English
• Subjects: Alcohol use; Alcohol Use Disorders Identification Test; Alcoholism; Alleles; Anandamide; Drinking behavior; Drinking Motives; Enzymatic activity; Enzymes; Etiology; FAAH Polymorphism (C385A; rs324420); Fatty Acid Amide Hydrolase; Fatty acids; Gene polymorphism; Genotype & phenotype; Hydrolase; Metabolism; Polymorphism; Youth
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14552

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. Analyses of Covariance (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 drinking days (p = 0.045), significantly more frequent heavy episodic drinking (p = 0.003), and significantly higher alcohol‐related problems and consumption patterns (AUDIT score p = 0.045, AUDIT‐C score p = 0.02). Mediation analyses showed 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 could account in part for this association. Youth with a polymorphism in the gene encoding the endocannabinoid‐metabolizing enzyme FAAH (FAAH rs324420; A allele) were found to exhibit more frequent hazardous alcohol consumption, mediated in part by increased coping motives for alcohol use. Extending previous similar findings in individuals with alcohol use disorder, these results suggest that reduced endocannabinoid metabolism may be related to heavier alcohol use in youth prior to the onset of chronic drinking problems, perhaps due to differences in negative reinforcement.