Background <p>New psychoactive substances (NPS) pose a rapidly evolving public health challenge due to their diverse chemical structures and psychoactive effects, necessitating a comprehensive understanding of their classification, mechanisms of action, and detection.</p> Objectives <p>Recognizing critical gaps in the understanding and management of NPS, this review aimed to synthesize current liter-ature. Specifically, we sought to elucidate the evolving classifications of NPS, delineate their underlying molecular mechanisms of action to inform therapeutic strategies, and critically evaluate existing detection methodologies to ad-dress current analytical limitations, thereby providing an essential, integrated perspective on this rapidly changing landscape.</p> Methods <p>A narrative literature review was conducted to analyze NPS classification, molecular mechanisms, and detection techniques. Searches were performed across Web of Science, Scopus, PubMed, and Elsevier, using keywords such as “synthetic cathinones”, “designer drugs”, “new psychoactive substance(s)”, “detection of new psychoactive sub-stances” and “toxicology.” Inclusion criteria prioritized studies primarily focused on NPS with clearly defined com-pounds (e.g., UNODC, EMCDDA classifications) and published within the last four years. Eligible publications en-compassed in vivo and in vitro studies, original research, and various review types. Exclusion criteria involved liter-ature outside the specified timeframe and studies on established drugs of abuse or licit substances, unless a direct comparative analysis with NPS was presented.</p> Results <p>The review synthesized a classification framework for NPS, detailed the molecular mechanisms underlying their psychoactive effects, and summarized current detection methodologies. Furthermore, it underscored the significant health risks associated with NPS use, including addiction, psychological disturbances, organ toxicity, and fatal outcomes.</p> Conclusion <p>The continued emergence and proliferation of NPS necessitate ongoing research to fully characterize their specific effects and associated risks. This review provides a foundational synthesis of current knowledge, not only supporting the development of evi-dence-based interventions to mitigate their public health impact, but also serving as a catalyst for new research direc-tions aimed at a deeper understanding and more effective management of these evolving compounds.</p> Graphical abstract <p></p>