Evidence map›Paper›PMID 38128606›Full record

ArticleNeuropharmacology2024

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine.

Safiyah M Sadek, Shailesh N Khatri, Zachary Kipp, Kelly E Dunn, Joshua S Beckmann, William W Stoops, Terry D Hinds, Cassandra D Gipson

Open access · hybridAbstract read
In one paragraph

Article in Neuropharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Validation of an oral self-administration model of xylazine use in mice.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Ketamine enhancement of dexmedetomidine attenuation of methamphetamine-induced agitation in rats.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Xylazine exacerbates fentanyl-induced respiratory depression and bradycardia.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  16. Article
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Safiyah M SadekDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Shailesh N KhatriDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Zachary KippDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Kelly E DunnPsychiatry and Behavioral Sciences Department, Johns Hopkins University, Baltimore, MD, USA.
Joshua S BeckmannDepartment of Psychology, University of Kentucky, Lexington, KY, USA.
William W StoopsDepartment of Behavioral Sciences, University of Kentucky, Lexington, KY, USA.
Terry D HindsDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Cassandra D GipsonDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: cdgips2@uky.edu.
University of Kentucky · USBehavioral Pharma (United States) · US

Funding

Neurobehavioral mechanisms underlying xylazine and fentanyl co-use and withdrawalR01DA058933 · NIDA · UNIVERSITY OF KENTUCKY · PI Cassandra D Gipson-Reichardt, Terry D Hinds · 2023 to 2026
$2.0M
Neuroinflammatory and glutamatergic mechanisms of nicotine seekingR01DA046526 · NIDA · UNIVERSITY OF KENTUCKY · PI GIPSON-REICHARDT, CASSANDRA D · 2019 to 2023
$1.9M
Glutamergic Mechanisms in Opioid and Cocaine Co-UseR33DA049130 · NIDA · UNIVERSITY OF KENTUCKY · PI GIPSON-REICHARDT, CASSANDRA D, STOOPS, WILLIAM WALTON · 2022 to 2024
$1.9M
Cholinergic modulation of glutamatergic signaling in nicotine addiction and relapseR21DA044479 · NIDA · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI GIPSON-REICHARDT, CASSANDRA D · 2018 to 2019
$461k
Contributions of Progestins Independently and Interactively with Contraceptive Estrogen to Nicotine UseR21DA055879 · NIDA · UNIVERSITY OF KENTUCKY · PI GIPSON-REICHARDT, CASSANDRA D · 2022 to 2023
$435k
Glutamergic Mechanisms in Opioid and Cocaine Co-UseR21DA049130 · NIDA · UNIVERSITY OF KENTUCKY · PI GIPSON-REICHARDT, CASSANDRA D, STOOPS, WILLIAM WALTON · 2020 to 2021
$402k
NIDA NIH HHS R01 DA046526NIDA NIH HHS R01 DA058933NIDA NIH HHS R21 DA044479NIDA NIH HHS R21 DA049130NIDA NIH HHS R21 DA055879NIDA NIH HHS R33 DA049130
6 · The paper itself

Abstract

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

Indexed as

Substance Withdrawal SyndromeXylazineAcute DiseaseAnalgesics, OpioidAnimalsBody WeightClonidineFemaleFentanylMaleRatsWeight LossAnalgesics, OpioidClonidineFentanyllofexidineXylazineBody weightDemandDose-responseFentanylLofexidineSelf-administrationWithdrawalXylazine

Identifiers

PMID38128606
PMCPMC10843705
OpenAlexW4389991524

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.