[Drug Dependence and Toxicity of Law-Evading Drugs: Their Mechanisms Explored from Basic Research].

The number of law-evading chemical substances that pose serious health risks to humans is increasing worldwide, including Japan and the Western world, and their abuse is becoming a serious social problem. Analysis of the chemical substances in these herbal products revealed the presence of synthetic cannabinoids. This review summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids as a group of chemical substances contained in these products. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids by using animals and cell cultures. In a place-conditioning study, the synthetic cannabinoids produced a significant conditioned-place preference. The rewarding effects of synthetic cannabinoids were completely suppressed by a cannabinoid CB1 receptor antagonist. Administration of synthetic cannabinoids to primary striatal culture caused cell death in a dose-dependent manner. Our findings show that the CB1 receptor might be involved in the expression of synthetic cannabinoid-induced rewarding effect. These behavioral data indicate that synthetic cannabinoids have a psychic-dependence liability. Furthermore, our data from primary striatal culture indicate that synthetic cannabinoids have strong neurotoxicity. These behavioral and neurochemical data indicate that synthetic cannabinoids might have strong adverse effects and a psychic-dependence liability.