SCIENTIFIC ABSTRACT 

Ketamine (KET) is a synthetic drug traditionally used as anaesthetic and more recently as antidepressant. However, its psychoactive effects have also driven an increase in illicit consumption, especially in Europe, raising public health concerns. Traditional epidemiological tools face limitations for real-time drug monitoring, positioning wastewater-based epidemiology (WBE) as a promising alternative for population-level surveillance. Since KET is excreted largely unmetabolized or as the metabolite norketamine (NKET) in urine, its quantification in wastewater can provide valuable insights into community drug use. Nonetheless, distinguishing between licit (prescription) and illicit sources—or direct disposal into sewers—remains challenging. Given that KET and NKET are chiral compounds, enantiomeric profiling can serve as a complementary approach to differentiate between pharmaceutical and illicit inputs. 

Hence, this two-year project aims to develop, validate, and apply a WBE-based analytical methodology combined with enantiomeric analysis to estimate KET use and identify its sources in Spain as a pilot study. Wastewater samples collected from 10 wastewater treatment plants across the country will be analysed to assess spatial and temporal trends. These data will be integrated with information on medical prescriptions and seized samples to discriminate between legal and illegal KET inputs. The results will enhance understanding of KET consumption dynamics and provide a robust framework for monitoring KET use all over the world. 

LAY SUMMARY 

Ketamine, an anaesthetic and emerging antidepressant, is increasingly misused illicitly, raising public health concerns in Europe. This project develops and applies a wastewater-based epidemiology and enantiomeric profiling approach to quantify ketamine use and distinguish legal from illegal sources, enhancing real-time monitoring of this psychoactive substance in any country