Wastewater analysis as a global toxicovigilance tool for the monitoring of new psychoactive substances.

New psychoactive substances are a group of synthetic or naturally occurring drugs that mimic the effects of controlled illicit drugs. With limited information around potency, effects and health risks, there is international concern around their use and thus surveillance efforts are needed for public health. This study presents a global assessment of new psychoactive substances in influent wastewater from 52 sites across 20 countries during the 2022/2023 New Year period. Using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry, 21 new psychoactive substances were detected with mitragynine, 3-methylmethcathinone, and eutylone being the most prevalent. Notably, 3,4-methylenedioxy-PV8 was identified for the first time in sites in Australia and the United States. A retrospective analysis of population normalised mass loads for 3-methylmethcathinone at European sites revealed downward trends in 2022/2023 sampling period compared to the previous years, suggesting a possible impact of regional scheduling measures. Additionally, this work demonstrates the stability of new psychoactive substances in loaded cartridges for up to four months when stored at -20 °C. These findings highlight the value of wastewater-based epidemiology for global monitoring of emerging new psychoactive substances threats and policy evaluation.