The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions
- PMID:35054944
- PMCID: PMC8776007
- DOI: 10.3390/ijms23020761
The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions
Abstract
Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin's/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin's/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.
Keywords: addiction; cannabinoids; ghrelin signaling; growth hormone secretagogue receptor type A (GHS-R1A); nicotine/tobacco; opioids; preclinical and clinical research; review; stimulants.
Conflict of interest statement
We declare no conflict of interest.
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References
- European Commission Tobacco—Overview. 2020. [(accessed on 1 December 2021)]. Available online:https://ec.europa.eu/health/tobacco/overview_en.
- Drug-Related Deaths and Mortality in Europe. European Monitoring Centre for Drugs and Drug Addiction, Publication Office of the EU Luxemburg; Luxembourg: 2019.
- UNODC World Drug Report 2021. [(accessed on 1 December 2021)]. Available online:https://www.unodc.org/unodc/data-and-analysis/wdr2021.html.
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