Knowledge, Preference, and Adverse Effects of Xylazine Among Adults in Substance Use Treatment

This cross-sectional study evaluates aspects of xylazine adulteration of opioids among individuals entering substance use disorder treatment.


Introduction
Xylazine, an α 2 -agonist, is a veterinary tranquilizer that is increasingly found in nonmedical opioids in the US and is associated with increased risk for skin ulcerations and complications associated with opioid overdose reversal with naloxone (as a nonopioid sedative) 1 and opioid withdrawal management. 2 Qualitative research suggests the sedative effect of xylazine may be preferred by some due to its perceived ability to prolong the effect of fentanyl. 3However, knowledge is limited regarding public awareness, preference, adverse effects, and changes in the opioid withdrawal syndrome with xylazine exposure.This cross-sectional study evaluated these aspects of xylazine adulteration of opioids among patients entering substance use disorder treatment.

Methods
This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.Informed consent and review were waived because it was recognized as nonhuman participant research by the Johns Hopkins School of Medicine institutional review board.Individuals in 78 substance use treatment programs in the US, who reported nonmedical opioid use within 30 days prior to treatment were surveyed about xylazine adulteration from January to October 2023.Trac9, a commercial treatment outcomes tool, administered the assessments and shared the results via a data use agreement.
Respondents answered questions about demographics (including race and gender to assess for potential disparities) and xylazine awareness.The participants were asked to self-report race or ethnicity from a list which included the following options: African American, Asian, Hispanic or Latino, Native American, Native Hawaiian or Pacific Islander, White, or other.Those who were aware of xylazine were also asked about the perceived likelihood of past xylazine adulteration of opioids, lifetime exposure to xylazine, and desire and preference for xylazine.All respondents were asked about developing specific adverse effects or experiencing withdrawal symptoms.The complete survey can be found in the eAppendix in Supplement 1. χ 2 tests using Fisher exact post hoc analysis evaluated whether there were demographic differences in xylazine awareness, desire for xylazine, and preference for xylazine.Logistic regression was used to examine the association between the perceived likelihood of xylazine adulteration and the presence or absence of specific adverse effects and withdrawal effects; significance was set at α <.05, with Holm-Bonferroni correction used for post hoc tests. 4 1).reported xylazine-associated altered withdrawal symptoms.Skin lesions, increased sedation, loss of consciousness, and difficulty in reversing overdoses with naloxone were more common among persons who believed their opioids may have contained xylazine and/or preferred xylazine (Table 2).
However, only 2 of the 4 potential withdrawal effects-increased headaches during withdrawal and a sensation of burning (particularly when given naloxone)-were positively associated with past 30-day xylazine exposure.

Discussion
This study provides insight into xylazine's presence in the opioid market based on perceptions of individuals in substance use disorder treatment.Findings indicate a widespread lack of awareness among persons using opioids regarding risk for xylazine exposure and potential inclusion of xylazine within their opioid supply.Preference for xylazine was associated with increased adverse effects.A limitation of this study is that the sample consisted entirely of individuals within treatment programs, potentially limiting generalizability to others who use opioids.The lack of awareness of xylazine, coupled with reported hazardous adverse effects and altered withdrawal symptoms, emphasizes the urgent necessity for harm reduction initiatives to increase public awareness of xylazine and help mitigate xylazine exposure and associated consequences. 5ARTICLE INFORMATION Accepted for Publication: January 8, 2024.Published: February 28, 2024.doi:10.1001/jamanetworkopen.2024.0572Open Access: This is an open access article distributed under the terms of the License.© 2024 Hochheimer M et al.JAMA Network Open.Corresponding Author: Martin Hochheimer, PhD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Dr, Baltimore, MD 21224 (mhochhe1@jh.edu).

Table 1 .
Xylazine Knowledge and Preference With Patient DemographicsKnowledge and Adverse Effects of Xylazine Among Adults in Substance Use Treatment b Only those who endorsed having heard about xylazine were asked this question.cPvaluesin line with categories are for omnibus χ 2 test, those in line with responses are for the Fisher exact post hoc analysis.dTheoverallP value for knowledge of xylazine was <.001; for use of xylazine, .39;forpreferenceforxylazine, .11. e The overall P value for knowledge of xylazine was <.001; for use of xylazine, .16;forpreferenceforxylazine, .87.f i The overall P value for knowledge of xylazine was .07;foruse of xylazine, .02;forpreferencefor xylazine, .03.JAMA Network Open | Substance Use and AddictionJAMA Network Open.2024;7(2):e240572.doi:10.1001/jamanetworkopen.2024.0572(Reprinted) February 28, 2024 2/4 Downloaded from jamanetwork.comby guest on 03/10/2024 Overall, 1963 respondents (68%) reported adverse effects and 1163 respondents (41%)

Table 2 .
Results of Logistic Regressions Evaluating the Association Between the Estimator Questions and the Outcome Measures a Scale 0 to 5. b Scale 0 to 10. c Dichotomous.d Number of respondents to both variables.