Brain and Behavior, cilt.16, sa.5, 2026 (SCI-Expanded, Scopus)
Purpose: The global increase in the prevalence of substance use disorders (SUD) has resulted in higher mortality rates. While heroin use has decreased or stabilized, methamphetamine use is increasing, and the combined use of opioids and methamphetamine is becoming more common. FAAH is an enzyme that hydrolyzes endocannabinoid substances and plays a role in neurobehavioral processes. The aim of this study was to investigate the effect of the FAAH rs324420 polymorphism on SUD. Method: The study included 562 individuals who used methamphetamine (MUD, n = 148), opioids (OUD, n = 114), or both methamphetamine and opioids (OMCU, n = 150), as well as 150 healthy volunteers. The FAAH rs324420 polymorphism was analyzed by PCR-RFLP. All participants completed the Barratt Impulsiveness Scale-11 (BIS-11), Clinical Opiate Withdrawal Scale (COWS), Substance Craving Scale (SCS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II). Finding: The frequencies of the variant allele (A) were 21%, 13%, 16%, and 19% in OUD, MUD, OMCU, and controls, respectively. Genotype frequencies in all four groups were in Hardy–Weinberg equilibrium (p > 0.05). The CA genotype significantly reduced the risk of the disease compared to the reference genotype (OR = 0.578, 95% CI:0.343–0.973, adjusted p = 0.039). Craving scale score was higher in individuals who concurrently used opioids and methamphetamine (20.0; 13.0–28.0) than in those who only used opioids (18.0; 14.0–28.0) (p = 0.009). Conclusion: This study showed that the rs324420 CA genotype of the FAAH gene may confer a protective effect against methamphetamine use disorder. Future studies with larger sample sizes and additional phenotypic traits are recommended to further explore these findings in other populations.