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

Biomedicines. 2022 Jun 13;10(6):1398. doi: 10.3390/biomedicines10061398.


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.

Publication types

  • Review

Grants and funding

This research has been funded by the Drug Policies Department, Presidency of the Council of Ministers, Italy (project: “Effects of NPS: development of a multicentric research for the information enhancement of the Early Warning System” to MM), by local funds from the University of Ferrara (FAR 2020 and FAR 2021 to MM), by FIRB 2012 from the Italian Ministry of Education, University and Research (Grant no. RBFR12LDOW to F. De-Giorgio) and by local funds from the Catholic University of Rome (Linea D1 grants to F. De-Giorgio).