P-47 * HARMFUL EFFECTS OF LAW-EVADING HERBS AS A NEW TREND IN JAPAN: BEHAVIORAL AND CYTOTOXICOLOGICAL PROPERTIES OF SYNTHETIC CANNABINOIDS

Abstract

Introduction. Law-evading herbal products consist of finely chopped dry vegetative matter mixed with chemical substances, and the drugs are injurious to health. Analysis of chemical substances in herbal products clarified that they contain synthetic cannabinoids. Method. The present study investigates the behavioral and cytotoxicological properties of synthetic cannabinoid CP-55, 940 in mice. In the current behavioral analysis study, we investigated the effect that CP-55, 940 has on place conditioning in ICR mice. The cytotoxicological effects of CP-55, 940 were characterized in mouse striatal neurons of primary culture in vitro. Results. In a place-conditioning study, CP-55, 940 produced a significant conditioned-place preference. The rewarding effects of CP-55, 940 were completely suppressed by cannabinoid CB1 receptor antagonist AM251. Administration of CP-55, 940 in striatal primary culture caused cell death in a dose-dependent manner. Conclusion. Our findings demonstrated that the CB1 receptor might be involved in the expression of CP-55, 940-induced rewarding effect. Furthermore, our data on striatal primary culture indicate that CP-55, 940 has strong neurotoxicity. These behavioral and neurochemical data indicate that CP-55, 940 might have strong adverse effects and a psychic-dependence liability. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell culture (cytotoxicity analysis in vitro).