Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Centre de recherche du centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada; Department of Social and Preventive Medicine, Université de Montréal, Montréal, Québec, Canada.
Addict Behav. 2023 Feb;137:107545. doi: 10.1016/j.addbeh.2022.107545. Epub 2022 Nov 11.
The endocannabinoid system is implicated in psychiatric disorders and drug dependence. Within this system, fatty acid amide hydrolase (FAAH) metabolizes endocannabinoids. Individuals with A-group genotypes (C/A or A/A) of a common FAAH variant (rs324420; C > A; Pro129Thr) have slower enzymatic activity compared to C-group individuals (C/C genotype). Slow FAAH activity is differentially associated with alcohol and nicotine use.
Among European-ancestry participants in the NDIT study (n = 249-607), genotype associations with past-year binge drinking in young adults were estimated in logistic regression models. In adolescents, hazard ratios (HR) were estimated from Cox proportional hazards models to assess the FAAH genotype group association with time to drinking initiation and attaining drinking frequency outcomes. HR were also used to assess genotype effect on time to smoking initiation and attaining early smoking milestones (e.g., first inhalation, ICD-10 dependence).
Compared to those in the C-group, those in the A-group had higher odds of binge drinking at ages 20 (Odds ratio (OR) = 2.16, 95 % CI 1.36-3.42) and 30 (OR = 1.61, 95 % CI 1.10-2.36). Time to initiation of drinking and daily drinking was faster in adolescents in the A-group (HR = 1.39, 95 % CI 1.09-1.77 and HR = 2.24, 95 % CI 1.05-4.76, respectively). Time to smoking initiation was faster in the A-group (HR = 1.20, 95 % CI 1.04-1.39); however, time to smoking milestones among adolescent smokers was not consistently different for the A- versus C-groups (HR = 0.43 to 1.13).
Slow FAAH activity (A-group) was associated with greater risks for binge drinking, drinking initiation and escalation, and cigarette smoking initiation, but had little impact on the escalation in cigarette smoking behaviors.
内源性大麻素系统与精神疾病和药物依赖有关。在这个系统中，脂肪酸酰胺水解酶（FAAH）代谢内源性大麻素。与 C 组个体（C/C 基因型）相比，常见 FAAH 变体（rs324420；C>T；Pro129Thr）的 A 组基因型（C/A 或 A/A）个体的酶活性较慢。较慢的 FAAH 活性与酒精和尼古丁的使用呈不同相关。
在 NDIT 研究中的欧洲血统参与者（n=249-607）中，使用逻辑回归模型估计了基因型与年轻人过去一年酗酒的关联。在青少年中，使用 Cox 比例风险模型估计风险比（HR），以评估 FAAH 基因型组与饮酒开始时间和达到饮酒频率结果的关系。还使用 HR 评估基因型对吸烟开始时间和达到早期吸烟里程碑（例如，第一次吸入、ICD-10 依赖）的影响。
与 C 组相比，A 组在 20 岁（优势比（OR）=2.16，95%置信区间（CI）1.36-3.42）和 30 岁（OR=1.61，95%CI 1.10-2.36）时酗酒的可能性更高。在 A 组中，青少年饮酒开始时间和每日饮酒时间更快（HR=1.39，95%CI 1.09-1.77 和 HR=2.24，95%CI 1.05-4.76）。A 组的吸烟开始时间更快（HR=1.20，95%CI 1.04-1.39）；然而，在青少年吸烟者中，A 组与 C 组在吸烟里程碑上的时间并没有明显差异（HR=0.43 至 1.13）。
较慢的 FAAH 活性（A 组）与酗酒、饮酒开始和升级以及吸烟开始的风险增加有关，但对吸烟行为的升级影响很小。
