Effect of synthetic cannabinoids on blood–brain barrier

Introduction: In recent years, many adolescents have started using a popular legal alternative to marijuana called K2/Spice, made primarily of a blend of synthetic cannabinoids. Many of the effects of these compounds result from their action on the central nervous system (CNS), causing adverse effects and drug dependence among their users. The compound most commonly found in K2/Spice is the potent CB1 agonist JWH-018, and therefore most research efforts have focused on CB1 agonists. The role of other JWH compounds with potent affinity for CB2 has not been elucidated. JWH-015 and AM-630 are a cannabinoid CB2 agonist and antagonist, respectively. Little is known about their effects on the blood– brain barrier (BBB). Objectives: We hypothesized that JWH-015 and AM-360, which are both synthetic cannabinoids, will affect the CNS, specifically BBB integrity, permeability and gene expression. Materials and methods: The effects of JWH-015 and AM-630 were tested on an in vitro  BBB model, which was constructed with human astrocytes and human brain microvascular endothelial cells. The integrity and function of the in vitro  BBB was assessed by measuring transendothelial electrical resistance (TEER), FITC– dextran transport and JAM-2 expression. Results: The results showed the combination of synthetic cannabinoids JWH-015 and AM-630 caused a dose-dependent (1– 5μM) decrease in TEER values of the BBB. Conclusions: In our study, we observed that the combination of synthetic cannabinoids JWH-015 and AM-630 caused a decrease in TEER values of the BBB; therefore, comprising BBB integrity and increasing FITC– dextran transport and JAM-2 expression. These finding may further clarify the effects of synthetic cannabinoids and the role of CB2 on the CNS, specifically their degenerative or protective action on the BBB. Acknowledgements: Florida International University Biomedical Research Training Program Staff: Dr Juan Acuna MD, MSc, FACOG, Program Director; Dr Juan Lozano MD, MSc, Program Co-Director; Laura Boudon PhD, Associate Director, International Programs; Imam University Research Training Program Staff: Professor Khalid A Bin Abdurrahman MBChB, DPHC, ABFM, IAF (U of T), MHSc (MEd) Dean of College of Medicine; Sami Al-Daham, MD, Director of International Program; Amr Y Arkoubi MD, MBBS FRCSC Student’ s Supervisor. Financial support of this work was given in part by NIH grant: 1R01DA027049.