Exploring the Impact of Chirality of Synthetic Cannabinoids and Cathinones: A Systematic Review on Enantioresolution...

New psychoactive substances (NPSs) are emerging narcotics or psychotropics that pose a public health risk. The most commonly reported NPSs are synthetic cannabinoids and synthetic cathinones. Synthetic cannabinoids mimic the effects of Δ9-tetrahydrocannabinol (Δ9-THC), often with greater potency, while synthetic cathinones act as stimulants, frequently serving as cheaper alternatives to amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. While some synthetic cannabinoids exhibit chirality depending on their synthesis precursors, synthetic cathinones are intrinsically chiral. Biotargets can recognize and differentiate between enantiomers, leading to distinct biological responses (enantioselectivity). Understanding these differences is crucial; therefore, the development of enantioresolution methods to assess the biological and toxicological effects of enantiomer is necessary. This work systematically compiles enantioselectivity studies and enantioresolution methods of synthetic cannabinoids and synthetic cathinones, following PRISMA guidelines. The main aim of this review is to explore the impact of chirality on these NPSs, improving our understanding of their toxicological behavior and evaluating advances in analytical techniques for their enantioseparation. Key examples from both groups are presented. This review highlights the importance of continuing research in this field, as demonstrated by the differing properties of synthetic cannabinoid and synthetic cathinone enantiomers, which are closely linked to variations in biological and toxicological outcomes.