Background <p>Caffeine acts on the central nervous system by antagonizing adenosine receptors, promoting alertness as adenosine regulates sleep and wakefulness. It has also an indirect stimulating effect by increasing dopamine neurotransmission, mediated by A2A (ADORA2A) and D2 (DRD2) receptors, which are co-localized in dopamine-rich brain regions.</p> Purpose <p>This study investigates the association between polymorphisms in the <i>ADORA2A</i> and <i>DRD2</i> genes and symptoms of anxiety, inattention, hyperactivity/impulsivity, as well as caffeine consumption in healthy adults. Additionally, we assessed correlations between caffeine consumption and these behavioral traits.</p> Methods <p><i>ADORA2A</i> variants (rs2298383 and rs3761422) and <i>DRD2</i> variants (rs2283265 and rs1076560) were analyzed in a sample of 315 Brazilians of European descent. Caffeine consumption was measured with a custom questionnaire, while anxiety, inattention, and hyperactivity/impulsivity symptoms were evaluated using standardized scales.</p> Results <p>Significant associations were found between <i>ADORA2A</i> variants and inattention symptoms, along with a synergistic effect between <i>ADORA2A</i> and <i>DRD2</i> risk haplotypes on these symptoms. However, we found no significant association between genetic variants and caffeine consumption. Caffeine intake was positively correlated with anxiety, inattention, and hyperactivity/impulsivity symptoms.</p> Conclusion <p>Our study provides evidence supporting the relationship between caffeine consumption and behavioral traits, including anxiety and ADHD symptoms. Furthermore, it demonstrates that the <i>ADORA2A</i> and <i>DRD2</i> genes influence symptoms of inattention. Taken together, these insights emphasize the importance of integrating genetic, nutritional, and behavioral data, and reinforce the need for future research in personalized nutrition to consider the potential implications for mental health.</p>