Serum zonulin, brain-derived neurotrophic factor, and oxidative stress levels in individuals using paper (a4) impregnated with synthetic cannabinoids

Sibel Kulaksızoğlu^1*Ali Erdoğan²Oğuzhan Tosun²Zeynep Yaren Görgülü²Esra Acar²Yavuz Kireç²Sercan KARABULUT²Burak Kulaksızoğlu²Buket Cinemre²Özmen Metin²

• ¹Antalya Eğitim ve Araştırma Hastanesi, Antalya, Türkiye
• ²Akdeniz Universitesi Tip Fakultesi, Antalya, Türkiye

Introduction: A4 is paper impregnated with synthetic cannabinoids, used as a novel psychoactive substance. The aim of this study was to investigate serum zonulin, brain-derived neurotrophic factor (BDNF), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) in patients predominantly using synthetic cannabinoid-impregnated papers. Methods: Thirty patients with A4 use and 30 healthy volunteers (HC) were included. Peripheral blood was collected for zonulin, BDNF, TOS, TAS and OSI levels after 8-12 hours of fasting. Substance Craving Scale (SCS) was administered to the patient group. Results: Patients using A4 had lower BDNF levels (p=0.001) and higher TOS and OSI levels (p<0.001, p<0.001) compared to HC. Zonulin and TAS levels of both groups were similar (p>0.005 for both). No correlation was found between the SCS scores and zonulin, BDNF, TAS, TOS and OSI values (p>0.05 for all). When ROC analysis was performed, the cut-off value for BDNF in the patient group was ≤2.51 pg/mL, sensitivity was 66.7%, specificity was 63.3%, PPV was 76.0%, NPV was 76.0%, and area under the ROC curve was 0.744. The cut-off value for TOS was ≥14.51 μmol/L, sensitivity 70.0%, specificity 66.7%, PPV 77.7%, NPV 79.5%, area under the ROC curve 0.766. The cut-off value for OSI was ≥0.69, sensitivity 76.7%, specificity 63.3%, PPV 76.0%, NPV 81.3%, area under the ROC curve 0.773. Discussion: The findings suggest that A4 use may impair neuroplasticity and disrupt oxidative stress balance. BDNF, TOS, and OSI appear to be promising biomarker candidates for identifying individuals with A4 use.