Rationale: Ghrelin is a fast-acting hormone that is produced primarily by the stomach and by the brain although in smaller quantities. The regulation and the secretion of ghrelin are complex and not limited to aspects of feeding. Ghrelin exerts powerful effects on multiple processes, and it has been demonstrated that it mediates the rewarding properties of food as well as of drugs of abuse.
Objectives: The purpose of this review is to summarize the findings of preclinical and clinical studies related to ghrelin's possible role in addiction for each specific class of substances. Questions related to ghrelin's involvement in addiction are highlighted. Recurrent methodological issues that render the interpretation of the findings challenging are discussed. Also, the potential of targeting ghrelin as a pharmacologic treatment strategy for addiction is explored.
Results: Ghrelin signaling is implicated in the mediation of behavioral and biochemical effects of drugs of abuse that are cardinal for the development of addiction, especially for alcohol, nicotine, and stimulants. The available literature implicating ghrelin in opioid or cannabis use disorders is currently limited and inconclusive.
Conclusions: There is intriguing, although not always consistent, evidence for the involvement of ghrelin signaling in aspects of addiction, especially in the cases of alcohol, nicotine, and stimulants. Further research, particularly in humans, is recommended to replicate and expand on the findings of the current literature. Improved and novel methodologies that take into account the volatile and complex nature of ghrelin are required to clarify the inconsistencies of the findings.