Distinct serum endocannabinoid profiles in treatment-naïve Han Chinese children with ADHD: a case–control pilot study

Objective Although peripheral endocannabinoid system (ECS) signatures have been implicated in ADHD among European and American populations, evidence from Asian pediatric cohorts remains scarce. This study quantified serum concentrations of four major endocannabinoids—anandamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA)—in treatment-naïve Han Chinese children with ADHD and examined their associations with symptom severity as measured by the SNAP-IV scale. Methods This cross-sectional study enrolled 22 children with ADHD (aged 6–12 years, diagnosed per DSM-5, IQ > 70) and 25 healthy controls (aged 6–12 years). Serum endocannabinoids were quantified via liquid chromatography–tandem mass spectrometry (LC–MS/MS). Symptom severity was assessed with SNAP-IV subscales [inattention, hyperactivity/impulsivity, oppositional defiant disorder (OD)]. Group comparisons used t -tests, and correlations were analyzed with Spearman’s rank coefficient. Results Children with ADHD showed significantly lower OEA (1.21 ± 0.14 ng/mL vs. 1.65 ± 0.16 ng/mL) and PEA (0.69 ± 0.06 ng/mL vs. 0.86 ± 0.05 ng/mL) levels, higher 2-AG (1.94 ± 0.08 ng/mL vs. 1.72 ± 0.017 ng/mL, p = 0.001), and unchanged AEA (0.33 ± 0.05 ng/mL vs. 0.36 ± 0.05 ng/mL) compared to controls. In the ADHD group, OEA negatively correlated with OD scores (rs = −0.461, p = 0.031), but not with inattention or hyperactivity/impulsivity; other endocannabinoids showed no significant correlations. Conclusion Selective ECS alterations in pediatric ADHD, particularly reduced OEA/PEA and elevated 2-AG with OEA’s link to OD symptoms, may highlight potential blood-based biomarkers for diagnosis and monitoring, warranting further research into ECS-targeted therapies.