Temporal and spatial patterns of xylazine and medetomidine detected in the DEA's National Forensic Laboratory Information System (NFLIS) reports.

Xylazine and medetomidine are α2-adrenergic receptor agonists and sedatives that have recently emerged as adulterants in the U.S. illicit drug supply, complicating public health monitoring and response. In this cross-sectional study, we used data from the Drug Enforcement Administration's (DEA) National Forensic Laboratory Information System (NFLIS) from 1999 to 2024 to examine temporal and geographic trends in detections of these substances. We also identified the ten most common "co-reported" drugs, defined as substances found in the same seizures as xylazine or medetomidine that were submitted to NFLIS; however, these should not be interpreted as true polysubstance mixtures since they were not necessarily physically mixed. Overall, we found that xylazine reports increased from just 2 in 1999 to 149 in 2015, then surged from 9,330 in 2021 to 25,047 in 2024, with the past four years accounting for more than 90 % of all xylazine reports. Similarly, medetomidine reports rose from 12 in 2021 to 245 in 2023, then substantially increased to 2,276 in 2024. This increase was largely driven by the Northeast, where medetomidine reports increased from 5 in 2023 to 1,633 in 2024. Fentanyl was co-reported in 52.9 % of xylazine and 63.6 % of medetomidine reports, with the highest shares in the Northeast at 78.7 % and 89.1 %, respectively. These findings underscore the rapid spread of xylazine and medetomidine in the illicit drug market and their frequent co-reporting with fentanyl, highlighting the need for further public health surveillance and widespread distribution of harm reduction services to continue monitoring their spread across the U.S.