Xylazine abuse, the growing risk: A review of its effects, upsurge use and associated fatalities in the USA and Puerto Rico

Abstract

In the last decade, the opioid overdose epidemic has been exacerbated by the emerging drug of abuse, xylazine. This veterinary anesthetic, an alpha-2 agonist, not only potentiates the fatal effects of opioids but also causes toxic endothelial effects. This review aims to assess the impact of xylazine use and overdoses within the context of the opioid crisis as a public health issue. The research used data from scientific publications, state health reports, and analyses from the Institute of Forensic Sciences of Puerto Rico. The databases PubMed, Google Scholar, and Scopus were searched for relevant publications. The search strategy employed two groups of terms: the drug of interest (xylazine) and types of exposure (drug use, overdose, substance abuse, etc.). The initial search in PubMed was then extrapolated, and the search terms were adjusted for appropriate database syntax. According to the most recent publications and CDC data in the USA, approximately 95 % of fentanyl overdose cases involve xylazine, while the other 5 % of overdose cases are attributed solely to xylazine, predominantly administered intravenously. In the last four years, more than 4000 overdose deaths have been related to xylazine use; the northeastern United States had reported the most significant number of deaths. This number changes daily as reanalysis results and new data are published. Less than 50 % of states perform tests for xylazine detection or maintain statistical monitoring of overdoses related to this drug. The absence of testing impedes emergency room physicians from making accurate diagnoses, increasing the likelihood of fatal overdoses. This review highlights five major concerns: (1) The recognition of intoxication as a primary concern and the unavailability of alpha-2 antagonists for treatment. (2) The challenges in the clinical setting linked to xylazine abuse and its co-administration with substances like fentanyl and its analogs. (3) The necessity for robust government statistical resources for the unification and dissemination of critical overdose and emerging drug abuse detection information. (4) The need for effective rehabilitation programs, including psychosocial support and treatment interventions, to respond to this public health crisis. (5) The urgency for further research to understand the prevalence, toxic effects of chronic or acute use, and the clinical implications in xylazine users, including the development of alpha-2 antagonists for treatment. We conclude that addressing these concerns is crucial to working with the xylazine abuse situation.

Keywords: Alpha 2 agonist; Emerging drugs of abuse; Fentanyl; Opioids crisis; Overdose; Xylazine; alpha2 antagonist.

Figure 1:

Xylazine Detection in Drug-Use-Related Deaths in Puerto Rico (2022)

Figure 2

illustrates the correlation between the percentage increase in overdose deaths and the detection of xylazine in seized drugs, categorized by region. Ratios range from 1.68 to 6.69 across most regions, although the Midwest shows a notable disparity, likely due to insufficient testing in that area. Data from each year related to the number of overdose cases is presented in Figure 3.

Figure 3

This illustrates the DEA-reported number of xylazine-positive overdose deaths in combination with the seized drug cases by region. This figure shows that the South and Northeast regions report the highest incidence of xylazine presence. The data indicate significant regional variations in the impact of xylazine abuse, with these two regions being the most affected. Caution is warranted in interpreting data from the West and Midwest, as potential misreporting may arise from inadequate testing.