Laura M Best1,2, Jeffrey D Wardell3,4,5,6, Rachel F Tyndale1,2,4,7, Matthew D McPhee8, Bernard Le Foll1,2,3,4,7,9, Stephen J Kish1,2,3,4,7, Isabelle Boileau1,2,3,4, Christian S Hendershot3,4,7,8. 1. Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada. 2. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. 3. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 5. Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada. 6. Department of Psychology, York University, Toronto, ON, Canada. 7. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. 8. Department of Psychology, University of Toronto, Toronto, ON, Canada. 9. Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
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. 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.
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 FAAHC385A. 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 FAAHC385A 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.
Authors: Francisco Navarrete; María S García-Gutiérrez; Ani Gasparyan; Daniela Navarro; Francisco López-Picón; Álvaro Morcuende; Teresa Femenía; Jorge Manzanares Journal: Biomolecules Date: 2022-03-03