{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:48:42Z","timestamp":1770817722972,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 DA056646"],"award-info":[{"award-number":["R01 DA056646"]}]},{"name":"National Institutes of Health","award":["U18 DA052319"],"award-info":[{"award-number":["U18 DA052319"]}]},{"name":"National Institutes of Health","award":["U01 DA051079"],"award-info":[{"award-number":["U01 DA051079"]}]},{"name":"National Institutes of Health","award":["UH2\/UH3 DA041115"],"award-info":[{"award-number":["UH2\/UH3 DA041115"]}]},{"name":"National Institutes of Health","award":["UG3 NS134920"],"award-info":[{"award-number":["UG3 NS134920"]}]},{"name":"National Institutes of Health","award":["R01 DA035552"],"award-info":[{"award-number":["R01 DA035552"]}]},{"name":"National Institutes of Health","award":["R01 DA032910"],"award-info":[{"award-number":["R01 DA032910"]}]},{"name":"National Institutes of Health","award":["R01 DA013930"],"award-info":[{"award-number":["R01 DA013930"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant effects on the glucose level. These findings suggest that, like cocaine itself, the fentanyl\u2013cocaine polydrug can self-promote its rewarding effects via elevating the ghrelin level, and that the ghrelin system might serve as a potential pharmacological target for treatment of substance use disorders caused by polysubstance use involving fentanyl and cocaine. Additionally, based on the insulin data obtained in this study, the insulin level was always downregulated significantly and considerably, implying that the fentanyl and cocaine polydrug might have a stronger cardiovascular toxicity to the patients with insulin resistance and diabetes. Further studies are required to examine this possibility.<\/jats:p>","DOI":"10.3390\/ijms26052341","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T04:55:08Z","timestamp":1741236908000},"page":"2341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Fentanyl-Laced Cocaine on Circulating Ghrelin, Insulin, and Glucose Levels in Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Huimei","family":"Wei","sequence":"first","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise C.","family":"Maul","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annet","family":"Kyomuhangi","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Park","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddilynn L.","family":"Mutchler","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Guo","family":"Zhan","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","unstructured":"(2024, December 27). 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