Evidence for gender differences in the Amphetamine/Methamphetamine ratio in the hair of subjects undergoing Fitness-to-Drive testing

Background and aims: Retrospective analysis of hair testing data provides insights in drugs abuse patterns and improves results interpretation. Cases from subjects undergoing driving fitness assessment (2010-2020) were examined to evidence patterns in methamphetamine (MA) abuse.Materials and Methods: All cases with positive MA (>= 0.025 ng/mg) were included (n = 585). Data available were gender, age, MA and A (amphetamine) in hair (h), hair color/treatment, length of proximal hair. Cases with Ah/MAh <= 0.35 (n = 469) were arbitrarily selected to remove as many combined A, MA users. ANOVA was performed to detect Ah/MAh predictors. Results: No predictors affected Ah/MAh. A bimodal frequency distribution was observed. We clustered cases in two groups (1, Ah/MAh 0.025-0.070; 2, Ah/MAh 0.071-0.120) and performed logistic regression. Only gender exhibited significant difference across groups (p = 0.0080). Odds ratio for females falling into group 2 was 2.86 times higher (CI97.5 1.34-6.44). Conclusion: Literature data support the hypothesis that the two Ah/MAh groups represent different phenotypes of the CYP2D6-mediated MA N-demethylation. Whether gender plays a role in such difference could not be confirmed. However, these results provide further suggestion of an association of gender and pharmacogenomics with MA disposition, requiring these factors to be considered in future research.