ArticleExperimental and clinical psychopharmacology2024
Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats.
Article in Experimental and clinical psychopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Adverse maternal and neonatal effects associated with perinatal xylazine exposure: a systematic review.Journal of perinatology : official journal of the California Perinatal Association · 2026Pooled it
- Xylazine reduces methamphetamine-induced hyperlocomotion in rats through κ-opioid and α2-adrenoceptor mechanisms.Neuroscience letters · 2026Article
- An evaluation of N-acetylcysteine in a sequential oxycodone and cocaine rat self-administration model.Experimental and clinical psychopharmacology · 2026Article
- Individual differences in behavioral effects of xylazine and opioid-xylazine mixtures in male rats.Psychopharmacology · 2026Article
- Xylazine, veterinary anesthetic and recreational drug adulterant, reduces cephalic regeneration and alters defensive responding in planarians.Neurotoxicology · 2026Article
- Xylazine-induced diuresis in rats is attenuated by κ-opioid receptor and α2-adrenoceptor antagonists.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Nicotine self-administration suppresses both pro- and anti-inflammatory accumbens cytokines but does not induce apoptosis in female rats.Addiction neuroscience · 2026Article
- Pharmacokinetics of xylazine and fentanyl in patients presenting to the emergency department after non-fatal opioid overdose.Drug and alcohol dependence · 2026Article
- Review
- Xylazine's κ opioid agonist activity is not shared with other FDA-approved αbioRxiv : the preprint server for biology · 2026Article
- Reinforcing effects of fentanyl/xylazine mixtures in monkeys responding under a food-versus-drug choice procedure.Behavioural pharmacology · 2026Article
- Unmasking a neurotoxic duo: a comprehensive overview of fentanyl-xylazine crosstalk in kinase pathways.Frontiers in cellular neuroscience · 2026Article
- Within- and Between-Subject Analyses of the Effects of Chronic Xylazine on Negative Phototaxis in Two Planarian Species.Biomolecules · 2025Article
- Interactions between cardiorespiratory effects of fentanyl and xylazine and their reversal in male and female Sprague-Dawley rats.The Journal of pharmacology and experimental therapeutics · 2025Article
- "Anything can happen": experiences of people using opioids in a xylazine market.Harm reduction journal · 2025Article
- Xylazine exacerbates fentanyl-induced respiratory depression and bradycardia.The Journal of pharmacology and experimental therapeutics · 2025Article
- Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice.Psychopharmacology · 2025Article
- Multiple memory object-drug association task (MODAT) for the study of polydrug associations.Addiction neuroscience · 2025Article
- Antagonism of the antinociceptive effects of fentanyl and the veterinary anesthetic xylazine in mice.The Journal of pharmacology and experimental therapeutics · 2025Article
- Xylazine induces dopamine release and augments the effects of fentanyl.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl "high," alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 μg/kg/infusion) or withdrawal to our knowledge. We established a rat model of xylazine/fentanyl co-SA and withdrawal and evaluated outcomes as a function of biological sex. When administered alone, chronic xylazine (2.5 mg/kg, intraperitoneal) induced unique sex-specific withdrawal symptomatology, whereby females showed delayed onset of signs and a possible enhancement of sensitivity to the motor-suppressing effects of xylazine. Xylazine reduced fentanyl consumption in both male and female rats regardless of whether it was experimenter-administered or added to the intravenous fentanyl product (0.05, 0.10, and 0.5 mg/kg/infusion) when compared to fentanyl SA alone. Interestingly, this effect was dose-dependent when self-administered intravenously. Naloxone (0.1 mg/kg, subcutaneous injection) did not increase somatic signs of fentanyl withdrawal, regardless of the inclusion of xylazine in the fentanyl infusion in either sex; however, somatic signs of withdrawal were higher across time points in females after xylazine/fentanyl co-SA regardless of naloxone exposure as compared to females following fentanyl SA alone. Together, these results indicate that xylazine/fentanyl co-SA dose-dependently suppressed fentanyl intake in both sexes and induced a unique withdrawal syndrome in females that was not altered by acute naloxone treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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