Blocking stomach-derived hormone could yield new treatment for opioid use disorder



Opioid use disorder is a leading cause of illness and death in the U.S., yet the number of available treatments is limited. Misuse of prescription opioids, such as oxycodone, are an important contributor to the current opioid crisis and the high rate of opioid overdose deaths.


In a series of experiments in animal models, IRP researchers led by Lorenzo Leggio, M.D., Ph.D., discovered that taking oxycodone increases levels in the blood of a hormone called ghrelin, which is normally involved in the body’s sense of reward or satisfaction after eating. Oxycodone also boosts the activity of the gene responsible for producing the ghrelin receptor in certain neurons in the brain that are involved in the rewarding properties of drug use. Treating mice with a compound that blocks ghrelin receptors in the brain reduced the animal’s self-administration of oxycodone and inhibited stimulation of the brain’s reward center using optogenetics, a technique that allows scientists to activate or inhibit specific neurons using light.


These results indicate that oxycodone influences the body’s ghrelin system in animal models and suggest that blocking the ghrelin receptor in the brain may represent a new pharmacological approach for treating opioid use disorder.


You ZB, Gardner EL, Galaj E, Moore AR, Buck T, Jordan CJ, Humburg BA, Bi GH, Xi ZX, Leggio L. (2022). Involvement of the ghrelin system in the maintenance of oxycodone self-administration: converging evidence from endocrine, pharmacologic and transgenic approaches. Mol Psychiatry. Apr;27(4):2171-2181. doi: 10.1038/s41380-022-01438-5.

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This page was last updated on Thursday, June 8, 2023