Cannabinoid profiling across toxicology samples in adolescents and young adults by route of administration and in relation to depression symptoms (2025)

Cannabis use is common, with diversity in cannabis products contributing to difficulty in accurately assessing the impact of cannabis use in vulnerable populations such as emerging adults. This study describes and assesses concurrence across toxicological matrices (oral fluid, plasma, urine, and hair) and self-reported cannabis use days. Further, it examines whether 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH, the primary metabolite of Δ9-tetrahydrocannbinol [THC]) concentration or use patterns varies by administration route (smoked flower or vaped concentrate) or predicts depression symptoms. Here, cannabis using (n = 70) and non-using (n = 24) adolescents and young adults (64% female; ages 18-21) were asked to contribute oral fluid, blood, urine, and hair for toxicological testing and self-reported past-90 days of cannabis use, including route of administration. Positive and negative toxicological results by matrix are presented, with sensitivity and specificity calculated. Correlations between THCCOOH concentration across matrices and self-report use were run. Analysis of variance models (ANOVAs) tested whether product type (smoked flower v. vaped concentrate) influenced cannabis use patterns, use to avoid withdrawal, or THCCOOH concentration. Regressions assessed cannabis metrics predicting depression symptoms, controlling for biological sex. All matrices demonstrated excellent specificity (100%), with largely adequate sensitivity (63-74%) except for oral fluid (12%). Self-report and toxicological metrics were significantly correlated (r's = .41-.97), except for avoiding withdrawal. THCCOOH concentration across matrices did not differ by route of administration group; groups also did not differ by self-reported use days or avoiding withdrawal symptoms (p's = .16-.66). Only plasma THCCOOH concentration predicted depression symptoms (beta = 4.43, p < .001). Taken together, toxicological matrices and self-reported cannabis use offer concurrent information in adolescents and young adults who regularly use cannabis. Plasma THCCOOH concentration uniquely predicted self-reported depression symptoms, indicating utility of toxicological cannabinoid concentration predicting clinical outcomes. Given the complexity of measuring cannabis use due to the plethora of available products and rise of new popular cannabinoids, use of toxicological results may offer new insights into clinical outcomes in those who frequently use cannabis.