Substances in fentanyl samples in the U.S. illicit drug supply: A decade of trends and regional variations using serial cross-sectional analysis.

Abstract

Fentanyl has become the dominant opioid in the illicit market in the U.S.; however, trends and variety of substances co-presented in samples involving fentanyl and fentanyl-related substances remain largely unexplored, limiting state public health responses. This paper aims to analyze temporal and geographical trends in substances co-reported with fentanyl in illicit drug supply across the U.S. from 2013 to 2023 to inform overdose prevention strategies. We conducted a serial cross-sectional analysis using data from the National Forensic Laboratory Information System. At national and state levels, we examined trends in co-reported substance categories: heroin, cocaine, psychostimulants, natural and synthetic cannabinoids, hallucinogens/dissociatives, club drugs, other illicit opioids, prescription opioids, illicit benzodiazepines, prescription benzodiazepines, and xylazine. Among 1,011,034 samples involving fentanyl and fentanyl-related substances, 25.8 % contained at least one additional substance category. Xylazine co-reporting increased significantly from 0.4 % in 2018 to 8.1 % in 2023, becoming the most frequently reported that year, overtaking heroin, which had been the most frequently co-reported substance overall. Geographically, fentanyl co-reporting with xylazine and cocaine was more prevalent on the East Coast, while psychostimulant co-reporting was more common on the West Coast. The rising prevalence of co-reporting xylazine and large geographic variations in co-reported substances highlight the shifts in the illicit drug supply. These findings emphasize the need for enhanced drug supply monitoring and region-specific overdose prevention strategies.