National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings

Perrone, Jeanmarie; Haroz, Rachel; D’Orazio, Joseph; Gianotti, Giacomo; Love, Jennifer; Salzman, Matthew; Lowenstein, Margaret; Thakrar, Ashish; Klipp, Stephanie; Rae, Lisa; Reed, Megan K.; Sisco, Edward; Wightman, Rachel; Nelson, Lewis S.

doi:10.1016/j.annemergmed.2024.01.041

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Furthermore, this trend is also being observed in deaths related to the use of these drugs. It is important to note that these fi gures do not represent the total number of cases that may have gone undetected by routine screenings [18][19][20][21][22]. Additionally, it must be emphasized that not all laboratories are equipped to identify xylazine and other novel substances that are being abused.…”

Section: Resultsmentioning

confidence: 99%

Opioid abuse, the escalating crisis, xylazine co-use, and the forensic toxicology challenges

Yoabel González,

Luz A

2024

Forensic Sci Today

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Introduction: The opioid crisis represents a longstanding public health emergency, significantly worsened by the concurrent use of xylazine. This epidemic has led to a surge in opioid-related fatalities, marking it as a pressing health crisis with global implications. The combination of xylazine with fentanyl and its analogs significantly increases the risk of overdose deaths. This study aims to analyze the current situation by reviewing scientific and governmental publications on the topic. Methods: Our analysis, established on data from PubMed, Google Scholar, and Scopus, highlights the pharmacological risks related to the combination of xylazine and synthetic opioids, such as fentanyl. It underlines the increased chances of fatal overdoses due to this combination. Results: The research associates weaknesses in current forensic toxicology screenings that fail to effectively detect these dangerous compounds. The illegal synthesis of these substances is a key challenge in directing the emergency. The combination of xylazine with synthetic opioids shows a significant public health risk, worsening the already critical opioid crisis. There is a critical need for improved drug detection and analysis methods to combat this growing challenge. Conclusion: Developing forensic toxicology screenings to precisely identify the presence of these substances is crucial for both the diagnosis and prevention of fatal overdoses. Our findings emphasize the requirement for immediate and concerted efforts to address the complexities of the opioid epidemic and highlight the potential consequences of public health strategies intended to mitigate this crisis.

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Section: Resultsmentioning

confidence: 99%

Opioid abuse, the escalating crisis, xylazine co-use, and the forensic toxicology challenges

Yoabel González,

Luz A

2024

Forensic Sci Today

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“…The current study provides a model that not only reflects the intricacies of human fentanyl dependence but also paves the way for future exploration into interactions with other drugs, neurobiological mechanisms underlying FUD and therapeutic treatments. For example, xylazine is commonly used in combination with fentanyl (88) and the two interact together (89). Xylazine has also recently been shown to have independent effects on kappa opioid receptors that may act to potentiate the effect of fentanyl (90).…”

Section: Discussionmentioning

confidence: 99%

Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice

Chen,

Xiao,

Kimbrough

2024

Preprint

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BackgroundThe rise in overdose deaths from synthetic opioids, especially fentanyl, necessitates the development of preclinical models to study fentanyl use disorder (FUD). While there has been progress with rodent models, additional translationally relevant models are needed to examine excessive fentanyl intake and withdrawal symptoms.MethodsThe study performed intravenous self-administration (IVSA) of fentanyl in male and female C57BL/6J mice for 14 days. Mechanical pain sensitivity during withdrawal was assessed using the von Frey test. Anxiety-like behavior was evaluated via the open field test one-week into abstinence and incubation of craving for fentanyl was assessed four weeks into abstinence.ResultsBoth male and female mice demonstrated a significant escalation in fentanyl intake over the 14 days of self-administration, with significant front-loading observed in the final days of self-administration. Increased mechanical pain sensitivity was present from 36- to 48-hour into withdrawal and increased anxiety-like behavior was found 1 week into abstinence. Four weeks into abstinence, mice showed significantly higher active lever pressing than the final self-administration session prior to abstinence.ConclusionsThe study establishes a translationally relevant mouse model of IVSA of fentanyl, effectively encapsulating critical aspects of FUD, including escalation of drug intake, front-loading behavior, withdrawal symptoms, and prolonged craving for drug into abstinence. This model offers a robust basis for further exploration into behavioral and neurobiological mechanisms involved in fentanyl dependence and potential therapeutic strategies.

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Jiang,

Connolly,

Strahan

et al. 2024

MMWR Morb. Mortal. Wkly. Rep.

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National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings

Cited by 6 publications

References 21 publications

Opioid abuse, the escalating crisis, xylazine co-use, and the forensic toxicology challenges

Opioid abuse, the escalating crisis, xylazine co-use, and the forensic toxicology challenges

Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice

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

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