Synthetic Cannabinoid Use is Associated with Higher Systemic Inflammatory Indices than Cannabis Use in Adolescents

The growing use of cannabis and synthetic cannabinoids (SCs) among adolescents raises concerns about their distinct physiological effects. This retrospective case-control study evaluated systemic inflammatory indices in 88 adolescents with cannabinoid use disorder (CUD) (mean age = 16.42 +/- 1.06 years; 51.1% male)-subdivided into Cannabis-CUD, SC-CUD, and Dual-CUD groups-compared with 50 healthy controls (mean age = 16.14 +/- 0.80 years; 40% male). & Idot;nflammatory indices, neutrophil-, basophil-, monocyte-, and platelet-to-lymphocyte ratios (NLR, BLR, MLR, PLR, dNLR, and NLPR), and systemic inflammatory indices (SII, SIRI, and AISI), were analyzed using ANOVA and ROC curve analysis. NLR, dNLR, BLR, SII (all p < .001), and NLPR, PLR, SIRI, AISI (p < .05) were significantly higher in the CUD group compared to healthy controls. Compared to controls, SC-CUD showed significantly higher inflammatory indices (p < 0.001 for NLR, BLR, and SII), while Dual-CUD showed moderate elevations (p = 0.009, p = 0.027, and p = 0.003 for NLR, BLR, and SII, respectively). For cannabis-CUD, BLR was the only marker that significantly differed from controls (p = 0.019). ROC analysis identified BLR (AUC = 0.72), SII (AUC = 0.71), and NLR (AUC = 0.70) as the strongest predictors of CUD. These findings highlight the comparatively higher inflammatory indices observed in the synthetic cannabinoid groups and suggest that blood-based indices may help identify adolescents at elevated physiological risk associated with cannabinoid use.