From 2012 to 2014 in Japan, a total of 214 cases of motor vehicle collisions were attributed to the use of illegal drugs by drivers. In 93 out of 96 investigated cases, the causative agents were 22 kinds of synthetic cannabinoids (SCs). Those SCs can be grouped into three groups according to the timeline of use and their chemical structures. The first generation SC naphtoyl indole derivatives, such as MAM-2201, were used in 2012 and disappeared by governmental overall regulations in Spring, 2013. Instead, quinolinyl ester indoles (second generation SC, such as 5F-PB-22) and indazole carboxamides (third generation SC, such as 5F-AB-PINACA) appeared thereafter with much stronger potencies. An outbreak of SC occurred in Summer, 2014 with one of the strongest SCs, 5F-ADB. The common signs observed in the SC-abused drivers are impaired consciousness, anterograde amnesia, catalepsy with muscle rigidity, tachycardia, and vomiting or drooling. Since the third generation SCs are extremely potent CB1 agonists (only a small amount is required) and instable in blood, it is very difficult to detect SCs in biological samples. Actually, only in one third of the cases, SC could be detected in blood or urine.