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Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy‐Drinking Youth
Author(s) -
Best Laura M.,
Wardell Jeffrey D.,
Tyndale Rachel F.,
McPhee Matthew D.,
Le Foll Bernard,
Kish Stephen J.,
Boileau Isabelle,
Hendershot Christian S.
Publication year - 2021
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14552
Subject(s) - fatty acid amide hydrolase , alcohol use disorders identification test , mediation , psychology , endocannabinoid system , genotype , alcohol , poison control , medicine , injury prevention , genetics , biology , environmental health , cannabinoid receptor , biochemistry , receptor , political science , law , gene , agonist
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.