Inhomogeneities in herbal mixtures: a serious risk for consumers

The most frequent form of consumption of cannabinoid receptor agonists (CRAs), often referred to as synthetic cannabinoids, is smoking of herbal mixtures often obtained via the Internet. However, because the plant material is either sprayed with or soaked in a drug solution, one of the main health risks in using these products is made up by the inhomogeneity in the content of active ingredient(s) and distribution within the mixtures. In the present study, 311 herbal mixtures covering 31 different brands seized from an online retailer in 2012 were analyzed quantitatively by high-performance liquid chromatography with diode array detection after screening by gas chromatography–mass spectrometry. Both interpackage and intrapackage CRA content variation were investigated by sampling without prior homogenization to reflect drug user behavior. The results showed that it is impossible for the consumer to safely dose these drugs, and that two joints of herbal mixture prepared from the same package could contain significantly different amounts of the active substance. Therefore, accidental overdosing is likely to occur frequently. In some products, interpackage variability of up to 33 % [standard deviation (SD)] and intrapackage variability of up to 20 % (SD) were observed. Another major health risk is posed by the substitution of a CRA in a herbal mixture without changing the brand name. In almost all cases when such a substitution was observed, there was a pronounced difference in the binding affinities of the respective CRA without a noticeable change in the amount added to the plant material. These findings can partly explain the high number of unintended intoxications that require hospitalization after use of these drugs.