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New Street Drugs Xylazine + Fentanyl Replacing "street heroin" - Widespread Distribution of Xylazine Detected Throughout the United States in Healthcare Patient Samples
  Journal of Addiction Medicine January 6, 2023
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Xylazine has emerged as a drug of concern, predominantly as an adulterant in substances such as cocaine, heroin, and illicitly manufactured fentanyl.3-5
In the xylazine-positive samples, fentanyl was the most detected copositive analyte (96%). When considering traditional toxicology tests, other notable copositive drugs/classes include buprenorphine (48.9%), nicotine metabolites (48.9%), cocaine (44.7%), naloxone (37.7%), d-methamphetamine (33.6%), and delta-9-tetrahydrocannabinol (THC 25.9%), among others.
Although published case reports regarding nonmedical use of xylazine were published as early as the 1980s, adverse effects, including overdose, secondary to use or exposure, have become increasingly reported in the past few years.9Updated data from the 2019 State Unintentional Drug Overdose Reporting System reveal an alarmingly steep increase of xylazine cases with 1,357 overdose deaths reported over the span of one year, approximately 3% of all overdose deaths in that year in the continental United States.4 Of the cases in which xylazine was detected, 39% listed xylazine on the death certificate as a contributing cause of death.6 The data also show evidence of a shift to illicitly manufactured fentanyl as the predominant coinvolved drug as fentanyl was detected in approximately 99% of all xylazine overdoses.3,4
Xylazine is an ⍺2-adrenergic agonist initially developed as an antihypertensive agent by Farbenfabriken Bayer AG (Leverkusen, Germany) in 1962, although severe hypotension and central nervous system (CNS) depression in early human clinical trials prevented its approval.1 The drug was reintroduced in the late 1960s and early 1970s as a veterinary medication for sedation and analgesia1 and is currently an unscheduled, approved drug by the US Food and Drug Administration for use as a sedative in horses, dogs, cats, deer, and elk.2 Pharmacokinetic and pharmacodynamic data primarily exist in animal species, with human data currently sparse.

Xylazine is a tranquilizer commonly added into the illicit drug supply and a likely contributor to overdoses because it does not respond to naloxone reversal. The objective of this study was to perform a retrospective data analysis on xylazine-positive samples collected from patients in various outpatient healthcare settings to illustrate geographic distribution and common copositive substances, which may also contribute to risk of adverse events.
Samples for which providers ordered testing for xylazine were subjected to enzymatic hydrolysis, extracted, and analyzed using liquid chromatography-tandem mass spectrometry. Retrospective analysis was performed on xylazine-positive samples collected from April 2021 to March 2022, to include geographic location and copositive substances.
Xylazine was identified in 413 of 59,498 samples from adults aged 20-73 years and originated from 25 of the 39 states where xylazine testing was ordered. The most common routine substances detected with xylazine were fentanyl, buprenorphine, naloxone, cocaine, d-methamphetamine, and delta-9-tetrahydrocannabinol. The most common designer drugs detected included fentanyl analogs, isotonitazene, and designer benzodiazepines.

Xylazine is geographically spread throughout the United States, indicative of a wide incorporation into the illicit drug supply. These findings differ from previous studies in that these samples originated from healthcare providers in routine care settings, where other reports typically involve overdose deaths. This analysis illustrates that routine testing for xylazine in outpatient settings can afford providers the opportunity to educate individuals and adjust harm reduction measures to potentially mitigate overdose risk.


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