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

Best, Laura M.; Wardell, Jeffrey D.; Tyndale, Rachel F.; McPhee, Matthew D.; Le Foll, Bernard; Kish, Stephen J.; Boileau, Isabelle; Hendershot, Christian S.

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

dc.contributor.author	Best, Laura M.
dc.contributor.author	Wardell, Jeffrey D.
dc.contributor.author	Tyndale, Rachel F.
dc.contributor.author	McPhee, Matthew D.
dc.contributor.author	Le Foll, Bernard
dc.contributor.author	Kish, Stephen J.
dc.contributor.author	Boileau, Isabelle
dc.contributor.author	Hendershot, Christian S.
dc.date.accessioned	2022-02-19T21:18:18Z
dc.date.available	2022-02-19T21:18:18Z
dc.date.issued	2021-03-15
dc.description.abstract	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.	en_US
dc.description.sponsorship	This research was supported by grants from the Canadian Institutes of Health Research (MOP-119444, MSH-130189 (CSH)), ABMRF/The Foundation for Alcohol Research (CSH) and the Ontario Mental Health Foundation (IB, CH). The authors acknowledge these additional sources of support for the present work: Canadian Institute of Health Research Doctoral Award GSD-159264 (LMB); Canada Research Chair in Etiology and Treatment of Alcohol Use Disorder (CSH); Canada Research Chair in Pharmacogenomics (RFT); Canadian Institutes of Health Research (CIHR) Foundation Grant FDN-154294 (RFT.); the Campbell Family Mental Health Research Institute of the Centre for Addiction and Mental Health (CAMH); the CAMH Foundation.	en_US
dc.identifier.citation	Best, L.M., Wardell, J.D., Tyndale, R.F., McPhee, M.D., Le Foll, B., Kish, S.J. Boileau, I., & Hendershot, C.S. (2021). Association of the fatty acid amide hydrolase C385A polymorphism with alcohol use severity and coping motives in heavy-drinking youth. Alcoholism: Clinical and Experimental Research, 45, 507-517.	en_US
dc.identifier.uri	https://doi.org/10.1111/acer.14552	en_US
dc.identifier.uri	http://hdl.handle.net/10315/39016
dc.language.iso	en	en_US
dc.rights	This is the peer reviewed version of the following article: Best, L.M., Wardell, J.D., Tyndale, R.F., McPhee, M.D., Le Foll, B., Kish, S.J. Boileau, I., & Hendershot, C.S. (2021). Association of the fatty acid amide hydrolase C385A polymorphism with alcohol use severity and coping motives in heavy-drinking youth. Alcoholism: Clinical and Experimental Research, 45, 507-517., which has been published in final form at https://doi.org/10.1111/acer.14552. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.	en_US
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 International	*
dc.rights.article	https://onlinelibrary.wiley.com/doi/10.1111/acer.14552	en_US
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Alcohol Use Disorders Identification Test (AUDIT)	en_US
dc.subject	drinking motives	en_US
dc.subject	Fatty Acid Amide Hydrolase (FAAH)	en_US
dc.subject	FAAH Polymorphism (C385A; rs324420)	en_US
dc.subject	youth	en_US
dc.title	Association of the Fatty Acid Amide Hydrolase C385A Polymorphism with Alcohol Use Severity and Coping Motives in Heavy-drinking Youth	en_US
dc.type	Article	en_US