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Abstract

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl and methamphetamine significantly increased plasma acyl-ghrelin (the active form of ghrelin) and total ghrelin concentrations. Additionally, the data also demonstrated for the first time that the use of fentanyl alone also significantly increased the plasma ghrelin concentrations. These findings imply that the ghrelin system could be a potential pharmacological target for the treatment of substance use disorders caused by polydrug use involving fentanyl and methamphetamine as well as the fentanyl use alone.

Document Type

Article

Publication Date

2025

Notes/Citation Information

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.3390/ijms262411806

Funding Information

This work was supported by the National Institutes of Health (R01 DA056646, U18 DA052319, U01 DA051079, UH2/UH3 DA041115, UG3/UH3 NS134920, R01 DA035552, R01 DA032910, and R01 DA013930).

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