Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones

Abstract

In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the pharmacotoxicological effects. To date, research into the acute pharmacological effects of new NPSs is ongoing and necessary in order to provide an appropriate contribution to public health. In fact, multiple examples of NPS-related acute intoxication and mortality have been recorded in the literature. Accordingly, several in vitro and in vivo studies have investigated the pharmacotoxicological profiles of these compounds, revealing that they can cause adverse effects involving various organ systems (i.e., cardiovascular, respiratory effects) and highlighting their potential increased consumption risks. In this sense, NPSs should be regarded as a complex issue that requires continuous monitoring. Moreover, knowledge of long-term NPS effects is lacking. Because genetic and environmental variables may impact NPS responses, epigenetics may aid in understanding the processes behind the harmful events induced by long-term NPS usage. Taken together, "pharmacoepigenomics" may provide a new field of combined study on genetic differences and epigenetic changes in drug reactions that might be predictive in forensic implications.

Keywords: forensic science; new psychoactive substances; pharmacoepigenomics.

Figure 1

Schematic illustration of the epigenetic changes that are of toxicological relevance for finding useful markers in a context of predicting cardiac and brain damage. Exposure to an NPS induces changes in the epigenetic landscape that could provide the basis for a panel of pharmacoepigenetic markers to predict toxicological damage to vital organs. The study of gene expression variations in a pharmacoepigenomic context is indicative of the variability between individuals in their responses to drugs or drugs of abuse.

Figure 2

Epigenetic inheritance.