Researchers found that xylazine was detected in an increasing proportion of fentanyl-positive urine drug test specimens across the United States between 2023 and 2025, even as urinary xylazine concentrations declined, suggesting that urine drug testing may complement existing surveillance of changes in the illicit drug supply.
In a retrospective cross-sectional study, the researchers analyzed 42,307 fentanyl-positive urine drug test specimens collected from adult patients between March 2023 and September 2025. One specimen per patient was included. Testing was ordered by clinicians practicing in substance use treatment, behavioral health, and primary care settings and performed by a national clinical laboratory using liquid chromatography with tandem mass spectrometry. The researchers evaluated temporal and regional trends in xylazine detection and concentration as well as associations with patient characteristics, treatment setting, copositivity for other substances, and fentanyl concentration.
The primary outcomes were changes in xylazine detection and urinary xylazine concentration over time. Secondary analyses assessed differences between Eastern and Western US regions and factors associated with xylazine detection among fentanyl-positive specimens.
Xylazine was detected in 17% of fentanyl-positive specimens. Detection increased throughout the study period in both regions, rising from 11% to 20% and 0% to 13% in the Eastern and Western United States, respectively. Although xylazine remained more commonly detected in the East, the overall increase during the study period was greater in the West.
In contrast, urinary xylazine concentrations declined in both regions. In the Eastern United States, concentrations decreased from 61.77 to 24.00 ng/mg creatinine between the first and last months of the study period. In the Western United States, concentrations declined from 28.62 to 20.64 ng/mg creatinine. The findings suggested that xylazine detection and concentration represented distinct measures of changes in the illicit drug supply.
Additional analyses showed that xylazine detection was more common in specimens that were also positive for heroin and in those with higher fentanyl concentrations. Detection remained less common in the Western United States, despite the larger increase observed in the West.
In an accompanying invited commentary, Janet E. Childerhose, PhD, ofthe Division of General Internal Medicine at The Ohio State University College of Medicine, wrote that the findings indicated xylazine detection and urinary concentration "are distinct outcome variables, and no single measure adequately characterizes adulterant changes in the drug supply." She added that expanding urine drug testing panels to include xylazine could strengthen clinical care and surveillance as the illicit drug supply continues to evolve.
The researchers noted several limitations. The analysis included only patients receiving care in substance use treatment, behavioral health, or primary care settings whose specimens were processed by a single national laboratory, limiting generalizability to the broader population of individuals using drugs. Urinary concentrations may also vary according to the timing of drug use, and the researchers did not evaluate emerging adulterants such as medetomidine that may increasingly be replacing xylazine in the illicit drug supply.
"[This] study shows the unique utility of [urine drug test] results as part of a comprehensive strategy for monitoring evolving and emerging drug threats," wrote lead study author Olivia K. Sugarman, PhD, MPH, of the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health, and colleagues.
Full disclosures of the study authors can be found in the study. Dr. Childerhose reported no conflicts of interest.
Source: JAMA Network Open, Editorial