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 multi-year 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 Biobío Region and analyzed for metabolites of cocaine (benzoylecgonine), cannabis (11-nor-9-carboxy-Δ9-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 (ρ = 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.
