Reported Xylazine Use Among Adults Aged ≥18 Years Evaluated for Substance Use Treatment — United States, July 2022–September 2023

Abstract

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022–September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past–30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

Introduction

Xylazine, a nonopioid sedative, has been increasingly detected in illegally manufactured fentanyl (IMF) products* and in U.S. overdose deaths (1). Most detected xylazine-involved overdose deaths also involve IMF (2); IMF-involved deaths with xylazine detected rose 276% in 21 jurisdictions during January 2019– June 2022 (3). Drugs sold as heroin increasingly contain IMF, which could lead persons seeking heroin to consume IMF, either knowingly or unknowingly (4,5). Xylazine has also been associated with skin lesions (6) that appear to be independent of the route of xylazine administration.^† To guide the development and implementation of prevention and response efforts, a cross-sectional U.S. study examining characteristics of adults evaluated for substance use treatment who reported IMF or heroin use and who also responded to questions about xylazine use was conducted.

Methods

Data Source

A convenience sample of U.S. adults aged ≥18 years evaluated for substance use treatment was identified using the validated, self-administered Addiction Severity Index-Multimedia Version (ASI-MV) clinical assessment tool^§ during July 2022–September 2023 (7). The ASI-MV tool, an instrument integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) and used for clinical treatment planning and triage purposes, is administered at substance-use treatment and other facilities or programs (including criminal justice programs, drug courts, and homeless services) and collects information on demographic characteristics, substance use patterns, routes of drug administration, and overdose history. Data were obtained from responses to the NAVIPPRO ASI-MV tool. Adults included in the analysis were those who responded to questions about xylazine use among those who reported IMF or heroin use. Xylazine was identified in ASI-MV as “xylazine (sometimes combined with heroin, fentanyl, or cocaine; sometimes known as sleep cut/tranq dope/Anestesia de Caballo).”

Statistical Analysis

Wilcoxon rank-sum tests for continuous variables and Pearson’s chi-square tests for categorical variables^¶ were used to compare the distribution of demographic characteristics for the following groups: 1) adults reporting ever versus never using xylazine, among adults reporting IMF or heroin as their primary lifetime substance use problem**; and 2) adults reporting recent (i.e., past–30-day) xylazine use^†† versus no recent xylazine use,^§§ among adults reporting recent IMF or heroin use. P-values <0.05 (two-sided) were considered statistically significant. Analyses were conducted using SAS (version 9.4: SAS Institute). This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.^¶¶

Results

Study Participants

Among 45,015 unique adults who completed assessments during the study period, 31,675 (70.4%) were assessed in the southern United States; 1,068 (2.4%) persons were excluded because they did not respond to the xylazine questions.*** Among the remaining 43,947 respondents, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance use problem, and 5,344 (12.2%) reported recent IMF or heroin use.^††† Among all 43,947 respondents, a total of 1,924 (4.4%) reported ever using xylazine.

Xylazine Use Among Adults Reporting IMF or Heroin as Their Primary Lifetime Substance-Use Problem

Among 6,415 adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. The median age of persons in this group was 34.0 years (IQR = 29.0–40.0 years); most were male (60.7%), non-Hispanic White (78.0%), had a high school education or less (73.5%), and had ever started treatment for substance use (77.6%) (Table). No statistically significant differences in age, sex, education, primary substance-use problem, or history of starting treatment for substance use were identified among adults who reported ever versus never using xylazine; however, a higher percentage of persons who ever used xylazine reported using at least one other substance recently (p<0.01). Further, the percentage of those who reported polysubstance use (use of two or more other substances apart from IMF or heroin and xylazine)^§§§ during the preceding 30 days was higher among those who had ever used xylazine (57.2%) than that among those who had never used it (36.1%) (p<0.01). Those reporting ever using xylazine reported more lifetime nonfatal overdoses from any drug (median = two) than did those who never used xylazine (median = one) (p<0.01).

The most common substances used during the preceding 30 days by persons reporting ever using xylazine were misused prescription opioids (63.4%),^¶¶¶,**** IMF (60.6%), and heroin (45.4%). Recent prescription opioid misuse was nearly twice as common among those who reported ever (63.4%) versus never (35.8%) using xylazine. The majority of respondents (58.5%) reported using xylazine by swallowing, snorting or sniffing, or smoking, without injection; nearly one third (31.7%) reported injecting xylazine.

Xylazine Use Among Adults Reporting Recent IMF or Heroin Use

Among 5,344 adults reporting recent (past–30-day) IMF or heroin use, 443 (8.3%) reported past–30-day xylazine use (Table). Compared with the percentage of adults who reported no recent xylazine use, higher percentages of persons with recent xylazine use were female (42.0% versus 34.7%; p<0.01) and reported other recent polysubstance use (84.9% versus 57.8%; p<0.01). Persons reporting recent xylazine use reported a median of two lifetime nonfatal overdoses from any drug compared with a median of one among those without recent xylazine use (p<0.01). Most persons (65.2%) reported using xylazine by swallowing, snorting or sniffing, or smoking, without injection; 30.7% reported injecting xylazine. Among persons reporting recent IMF or heroin use, a higher percentage of those reporting recent xylazine use reported other recent substance use (range = 11.3% [prescription stimulant misuse] to 94.6% [IMF]) than did persons who did not report recent xylazine use (range = 2.8% [prescription stimulant misuse] to 83.2% [IMF]) (all p-values <0.01).

Discussion

Among adults evaluated for substance use treatment and reporting IMF or heroin use during the past 30 days or as their primary lifetime substance use problem, those reporting xylazine use reported more past nonfatal overdoses; as well higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use than did those who did not report xylazine use. Whether xylazine increases IMF-involved overdose risk is not clear (5); a previous analysis found that overdose circumstances and other drug co-involvement were largely similar between IMF-involved deaths with and without xylazine detected (3). Reported xylazine exposure might be associated with higher numbers of nonfatal overdoses because both nonfatal overdoses (8) and xylazine exposure are associated with polysubstance use, consistent with the finding in this report. Although naloxone cannot reverse the effects of xylazine, its distribution should be expanded because xylazine is most commonly combined with IMF, the effects of which do respond to naloxone (3,5,9). More research is needed to understand whether xylazine use might indicate other polysubstance use or might be associated with unique withdrawal and dependence syndromes and the implications for treatment of concomitant opioid use disorder (5,9).

Data to guide development and implementation of recommendations for treatment of persons with xylazine use are limited; however, recent reviews have noted that persons with extensive xylazine-associated skin involvement might experience additional difficulties accessing needed services, including substance use treatment and wound care, which can, in turn, exacerbate substance use and interfere with wound healing (5,9). Reducing stigma associated with substance use, and specifically with wounds as a sign of substance use, is an important component of linking and retaining persons with substance-associated skin involvement in low-barrier substance use treatment programs as a means to help them access harm reduction services and wound care (5). Parameters for use and timing of clinical testing for xylazine use have not been clearly defined (5); however, persons who use illicit drugs, including opioids, cocaine or crack, or amphetamine-type drugs, have reported a desire for xylazine test strips (10). Expanding clinical care and drug checking programs (including, for example, provision of fentanyl and xylazine test strips) might facilitate engagement of persons who use drugs in harm reduction services and help them limit the potential for associated harms.

Limitations

The findings in this report are subject to at least seven limitations. First, xylazine use could be under- or overreported. Information was not available concerning the validity of self-reported xylazine use, including whether presence of xylazine was confirmed with test strips or whether respondents believed they consumed xylazine. Of note, xylazine or IMF is often mixed with other substances, and respondents might have been unaware of their exposures (2,3,10), potentially leading to underreporting of actual xylazine or IMF exposure. Second, ASI-MV data are self-reported and subject to social desirability, reporting biases, and recall error. Third, persons who use multiple substances might be more likely to have heard of xylazine and, therefore, more likely to report using xylazine. Fourth, the ASI-MV does not ask whether persons intentionally used xylazine or were simply exposed to it as an adulterant of other drugs. A survey of persons who inject drugs in Philadelphia found that whereas some persons might seek xylazine, most prefer not to use xylazine (4). This preference might be due to concerns about negative effects of xylazine, such as worsened withdrawal symptoms and wounds (2,4). Fifth, for each substance used, no start and end use dates were recorded; thus, identifying adults using xylazine and other substances simultaneously was not possible. Sixth, because of the study design, xylazine use without IMF or heroin (e.g., xylazine used with cocaine) was not reported. Future study is needed to explore the characteristics of this population and help them mitigate any associated harms. Finally, data are a convenience sample, and most assessments came from the southern United States; xylazine presence varies in the illicit drug supply across the United States.^†††† Thus, results might not be generalizable to all U.S. adults being assessed for substance use treatment.

Implications for Public Health Practice

Most fatal overdoses involving xylazine in the United States also involve IMF (2); to reduce fatal overdoses, linking and retaining persons who use xylazine in effective substance use treatment, including medications for opioid use disorder as indicated, and expanding naloxone distribution are critical. To help engage persons who use drugs in treatment, mitigate harms of drug use, and build trust among persons not yet ready for substance use treatment, jurisdictions can expand access to harm reduction services, including xylazine test strips and wound care. Broader interventions are needed to reduce stigma directed toward persons who use drugs and increase awareness of their treatment and service needs so that services can be accessed without judgment.