Xylazine: Pharmacology Review and Prevalence and Drug Combinations in Forensic Toxicology Casework

Xylazine, an alpha-2 receptor agonist used in veterinary medicine for its sedative and muscle-relaxant effects, has been reported in forensic toxicology casework since the 1980s. It is not approved for human use, but it is used as an adulterant in heroin and illicit fentanyl. The prevalence and concentrations of xylazine in 2.5 years (January 2019-June 2021) of driving under the influence of drugs (DUID) and medico-legal death investigation (MDI) cases was investigated, including other drugs detected in combination with xylazine. Of over 170,000 cases screened for xylazine, 97% were classified as MDI. Over the course of the study period, the prevalence and geographical spread of xylazine increased. Overall, 2.8% of DUID and 2.1% of MDI cases screened positive for xylazine with concentrations of 5.1-450 ng/mL (mean = 36 ng/mL) and 5.0-11,000 ng/mL (mean = 41 ng/mL), respectively. Two MDI cases which had xylazine concentrations of 9,100 and 11,000 ng/mL were drug overdose suicides that did not involve any opioids. Opioids, primarily fentanyl and/or a fentanyl byproduct/metabolite were detected in 100% of DUID and all but two MDI cases. After opioids, stimulants, phyto-cannabinoids and benzodiazepines were the most common drug classes detected in conjunction with xylazine in both DUID and MDI casework. In summary, xylazine exposure continues to increase, mostly through the adulteration of illicit opioids. There is an extensive overlap in the concentrations between living and deceased individuals, making it difficult to interpret the role of the drug in MDI or DUID cases without other case information.