In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties. This paper presents toxicological findings of synthetic cannabinoids in whole blood from some cases of severe intoxication including quantitative data from recreational users and a fatal intoxication. Samples were analyzed by liquid chromatography-tandem mass spectrometry in a scheduled multiple reaction mode after a basic liquid extraction. Twenty-nine synthetic cannabinoids were included in the method. In our data set of ~3000 cases, 28% were found positive for one or more synthetic cannabinoid(s). The most common finding was AM-2201. Most of the analytes had median concentrations of <0.5 ng/g in agreement with other published data. The emerging drugs MAM-2201 (n = 151) and UR-144 (n = 181) had mean (median) concentrations of 1.04 (0.37) and 1.26 (0.34), respectively. The toxicity of the synthetic cannabinoids seems to be worse than that of natural cannabis, probably owing to the higher potency and perhaps also to the presence of several different cannabinoids in the smoked incense and the difficulties of proper dosing. The acute toxic effects may under certain circumstances contribute to death.