These studies suggest that degradation or heating and thermolysis of the bulk chemicals or herbal products may result in inhalation of a completely different chemical or a mixture of chemicals. Furthermore, the data suggest that the volatility and thermolytic stability of the synthetic cannabinoids identified to date can vary dramatically, even with relatively modest changes in chemical structure, such that they are often difficult to predict with certainty. However, under typical conditions of use involving elevated temperatures, anticipated chemical exposures include lung irritants and known or suspected mutagens and carcinogens (e.g., naphthalene, isocyanatonaphthalene, 8-OH-quinoline, 1-naphthylamine, and 2-naphthylamine) as well as chemicals of unknown health impact.
In summary, identification and detection of the chemicals present in a bulk drug substance or formulation is clearly important for law enforcement efforts. However, as described above, the chemicals present in the substance or formulation may not be the same as those that are actually being inhaled and absorbed into the bloodstream. Understanding the chemical fate of synthetic cannabinoids during use, with emphasis on the actual chemicals of exposure and their metabolic products formed after absorption, is crucial in determining the health effects. Exposure to even minor chemical constituents may have profound implications, as demonstrated by the “frozen addicts” resulting from inadvertent exposure to MPPP, a trace impurity formed from overheating during the synthesis of the designer opiate meperidine.41
These drug users suffered extensive destruction of dopaminergic neurons in the substantia nigra, producing immediate and irreversible Parkinson’s disease symptoms. Determination of the chemical responsible for the Parkinson-like neuronal degradation was understood fully only after careful analytical and pharmacological assessment in multiple laboratory animal species.
In order to avoid similar painful lessons, research scientists need to continue careful assessment of abused substances, including their chemical exposure profiles and associated pharmacological and toxicological endpoints. Given the increasing number of synthetic cannabinoid variants available and their varying potency and toxicity, this evaluative process is critically necessary for effective prevention and treatment.