Xylazine effects on opioid-induced brain hypoxia

Choi, Shinbe; Irwin, Matthew R.; Kiyatkin, Eugene A.

doi:10.1007/s00213-023-06390-y

Cited by 20 publications

(12 citation statements)

References 44 publications

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“…The range of toxic doses in humans greatly varies from 40 mg to 2400 mg. 70 When combined with opioids such as fentanyl, xylazine can exacerbate the life-threatening potential of opioid use by worsening brain hypoxia and decreasing the lethal dose, potentially resulting in death. 70 One sequala of xylazine use that prompted awareness of adulteration by public health officials, increased the morbidity associated with opioid use disorder, and garnered media attention, is the apparent association of xylazine with "burnlike" skin and soft tissue infections in up to 38% of users. 76 These often occur in places other than the injection site.…”

Section: ■ Adverse Effectsmentioning

confidence: 99%

“…Multiple routes of administration, including oral, subcutaneous, and intravenous, contribute to this variability. The range of toxic doses in humans greatly varies from 40 mg to 2400 mg . When combined with opioids such as fentanyl, xylazine can exacerbate the life-threatening potential of opioid use by worsening brain hypoxia and decreasing the lethal dose, potentially resulting in death …”

Section: Adverse Effectsmentioning

confidence: 99%

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Classics in Chemical Neuroscience: Xylazine

Hoffman,

Giduturi,

Cordaro

et al. 2024

ACS Chem. Neurosci.

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Xylazine (also known as “tranq”) is a potent nonopioid veterinary sedative that has recently experienced a surge in use as a drug adulterant, most often combined with illicitly manufactured fentanyl. This combination may heighten the risk of fatal overdose. Xylazine has no known antidote approved for use in humans, and age-adjusted overdose deaths involving xylazine were 35 times higher in 2021 than 2018. In April 2023, the Biden Administration declared xylazine-laced fentanyl an emerging drug threat in the United States. In 2022, the Drug Enforcement Agency (DEA) reported nearly a quarter of seized fentanyl powder contained xylazine. This dramatic increase in prevalence has solidified the status of xylazine as an emerging drug of abuse and an evolving threat to public health. The following narrative review outlines the synthesis, pharmacokinetics, pharmacodynamics, and adverse effects of xylazine, as well as the role it may play in the ongoing opioid epidemic.

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Section: ■ Adverse Effectsmentioning

confidence: 99%

Section: Adverse Effectsmentioning

confidence: 99%

Classics in Chemical Neuroscience: Xylazine

Hoffman,

Giduturi,

Cordaro

et al. 2024

ACS Chem. Neurosci.

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“…For example, xylazine and other alpha-2 agonists such as clonidine and medetomidine enhance the antinociceptive potency of fentanyl in rats (Meert and De Kock, 1994). Xylazine also potentiates the hypoxic effects of fentanyl (Choi et al, 2023) and enhances fentanyl-associated lethality in rodents (Acosta-Mares et al, 2023; Smith et al, 2023). However, recent rodent studies suggest that xylazine actually decreases the abuse-related effects of fentanyl (Khatri et al, 2023; Sadek et al, 2024) and morphine (Samini et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Xylazine does not enhance fentanyl reinforcement in rats: a behavioral economic analysis

St. Onge,

Canfield,

Ortiz

et al. 2024

Preprint

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The adulteration of illicit fentanyl with the alpha-2 agonist xylazine has been designated an emerging public health threat. The clinical rationale for combining fentanyl with xylazine is currently unclear, and the inability to study fentanyl/xylazine interactions in humans warrants the need for preclinical research. We studied fentanyl and xylazine pharmacokinetic and pharmacodynamic interactions in male and female rats using drug self-administration behavioral economic methods. Fentanyl, but not xylazine, functioned as a reinforcer. Xylazine combined with fentanyl resulted in a xylazine-proportion dependent depression of behavior without significantly altering fentanyl reinforcement. Fentanyl and xylazine did not result in changes to pharmacokinetic endpoints. The present results demonstrate that xylazine does not enhance the addictive effects of fentanyl or alter fentanyl plasma concentrations. As there appears to be no pharmacologic rationale for their use in combination, these preclinical results suggest that the fentanyl/xylazine combinations may represent a novel form of chemical warfare.

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“…7,8 Additionally, worsening brain hypoxia has been proposed as one of the possible mechanisms contributing to xylazine-positive opioid-overdose deaths. 9 Perhaps more perplexing has been xylazine's ability to cause conspicuous wounds that are distinct from typical fentanyl injection site lesions. Although the culprit behind these wounds is not fully clear, it has been surmised that lower tissue oxygenation leading to vasoconstriction and diminished perfusion to the skin may be the cause.…”

mentioning

confidence: 99%