Abstract

Wastewater-based epidemiology (WBE) offers a powerful approach to monitoring community-level drug consumption by determining biochemical markers excreted into sewage network. This study presents the first multiyear regional WBE assessment in Chile, conducted under the Biobio Sentinel initiative between September 2022 and August 2024. A total of 3198 24-hour composite influent samples were collected weekly from 33 wastewater treatment plants (WWTPs) across the Biob & iacute;o Region and analyzed for metabolites of cocaine (benzoylecgonine), cannabis (11-nor-9-carboxy-Delta 9-tetrahydrocannabinol), and ketamine using validated SPE/LC-MS/MS method. Drug consumption was normalized to population equivalents and evaluated through temporal, spatial, and correlation analyses. Results revealed marked and contrasting trends: cocaine use increased more than tenfold (+1019 %), cannabis consumption declined by over 90 %, and ketamine emerged as a new psychoactive substance, rising from undetectable to measurable levels in multiple locations. Strong positive correlations were observed between cocaine and ketamine (rho = 0.83, p < 0.001), while cannabis showed inverse associations with both substances. Urban areas were identified as persistent consumption hotspots. These findings highlight a rapid transformation of the Chilean drug landscape, with stimulant-type substances gaining prominence over cannabinoids. The study demonstrates the feasibility and policy relevance of implementing WBE as a complementary surveillance tool alongside national drug surveys and seizure data, offering a scalable framework for real-time public health monitoring in Latin America.