From JWH-018 to OXIZIDS: structural changes in newly emerged synthetic cannabinoids in the European Union from December 2008 to December 2021

With new synthetic cannabinoid receptor agonist (SCRA) compounds appearing on the European drug market every year, regional early warning systems are key to detect, monitor, and respond to the threats posed by them. The European Union Early Warning System (EU EWS) implemented by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) started monitoring these substances back in 2008. Since then, various national, European, and international drug controls have been implemented aiming at tackling these compounds. As a response, new SCRAs have appeared in the market containing structural moieties not covered by controls in place, increasing the diversity of substances and complexity of forensic analysis.

All SCRAs under monitoring by the EMCDDA by the end of 2021 were organised according to their 4 structural elements: core, tail, linker, and linked groups. SCRA structural evolution has been analysed in tandem with European and international legislation (UN, China). This study describes the structural evolution of SCRAs that have appeared in the EU, employing an in-depth analysis of the core, linker, linked and tail groups. This data has been compiled into treemaps and histograms, and a timeline has been constructed displaying key structural milestones – by notification date to the EU EWS at the EMCDDA, and key legislative changes that have occurred since the first SCRA emerged.

Synthetic cannabinoids in Europe have diversified far from the original SCRA, JWH-018. This diversification has run in tandem with the introduction of legislation in a game of cat and mouse. The SCRA market is fast moving, with new structural groups appearing on the market less than 5 months after the introduction of a general SCRA ban in China. This work highlights the importance of maintaining a monitoring programme at the EMCDDA and around the world for an effective public health response.