Study suggests that there is a dysregulation of the ghrelin system in heavy alcohol drinkers

A recent experiment used intravenous infusions of alcohol in heavy drinkers and healthy controls to study the relationship between levels of ghrelin, a hormone that is produced in the stomach, and the effects of alcohol. Results showed that alcohol significantly reduced ghrelin levels over time when compared to placebo. Persons with higher baseline ghrelin levels reported stronger stimulant and sedative effects of alcohol. The study was published in Alcohol and Alcoholism.

Studies on heavy drinkers of alcohol in the past two decades have suggested that ghrelin, a 28-amino acid peptide, has a role in subjective experiences related to alcohol consumption. Ghrelin is thought to act on brain regions and neural circuits that are responsible for reward processing and stress regulation and to affect the craving for alcohol and subjective feelings related to its consumption. Aside from this, it has been identified as important in regulating appetite and food intake.

Studies have also shown that alcohol intake, both by drinking and when injected directly into the bloodstream through veins (intravenously), reduces ghrelin levels in both people with the alcohol use disorder and healthy individuals. On the other hand, administering ghrelin to individuals was shown to increase the craving for and drinking of alcohol. Ghrelin levels could also be reduced through forced intake of water.

To study the effects of alcohol on ghrelin levels and the relationship between ghrelin levels and subjective effects of alcohol in heavy drinkers, researcher Elisabeth Ralevski and her colleagues devised a study that included 12 heavy drinkers aged between 21 and 55 along with 20 healthy social drinkers between 21 and 30 years of age.

Heavy drinkers were people who consumed more than 10 standard alcoholic drinks per week and had between 1 and 5 episodes in which they drank multiple alcoholic drinks on the same occasion (more than 5 for men, more than 4 for women) per week. Eight of the heavy drinkers were male, 8 were single, and 5 of them were Black.

Participants were part of two larger studies and the current study analyzed the results from days when they were either intravenously administered alcohol or a saline solution, as a placebo through an infusion (intravenously means injected into the bloodstream through a needle inserted into a vein).

Researchers measured ghrelin levels in blood at 4 different time points – when participants came into the laboratory in the morning, immediately before the infusion, during the infusion and after the infusion. Alcohol/saline solution infusion lasted for 2 hours for heavy drinkers and 1 hour for healthy controls.

Participants completed assessments of the stimulant and sedative effects of alcohol (the Biphasic Alcohol Effects Scale), of feelings of being buzzed, high, drowsy and tired (the Visual Analog Scales), and of how many drinks they felt they consumed at a specific timepoint (the Number of Drinks Scale). The last scale actually asked the participant to assess the number of alcoholic drinks the infusion they received equals to. Participants were also asked to rate their craving for alcohol i.e., the desire for an alcoholic beverage at the time of asking, using a single item from the Yale Craving scale.

Results showed that alcohol infusion significantly reduced ghrelin levels compared to placebo (the saline solution infusion) over time. This, however, did not depend on the dose of alcohol. Baseline ghrelin levels, i.e., levels immediately after arriving in the laboratory (or fasting ghrelin levels, as participants were instructed not to eat anything since the previous evening) predicted the stimulant and sedative effects of alcohol. Participants with higher baseline ghrelin levels reported stronger stimulant and sedative effects than those with lower ghrelin levels.

Participants with higher ghrelin levels also assessed the amount of alcohol they received intravenously as higher. “Those with higher ghrelin levels reported that the amount of alcohol was more like five drinks, whereas those with lower ghrelin levels felt that the amount of alcohol was similar to about 3.5 drinks,” the authors reported and added that “Fasting ghrelin levels were significant predictors of feeling ‘buzzed’ and ‘drowsy’, but not feeling ‘high’ or ‘tired.'” Ghrelin levels were not associated with the craving for alcohol.

Comparison of heavy drinkers to healthy participants showed that alcohol infusions decreased ghrelin levels in both groups. However, ghrelin levels increased over time in healthy participants on the day when they received placebo, i.e., when they were infused with a saline solution. At that time, ghrelin levels remained almost the same in heavy drinkers i.e., recovered much more slowly.

“In sum, in heavy drinkers, intravenous alcohol significantly suppressed ghrelin levels, and ghrelin levels were related to subjective effects of alcohol. Although in both groups high dose of intravenous alcohol significantly and similarly reduced ghrelin levels, on the placebo day, ghrelin levels in heavy drinkers remained almost flat, whereas in healthy subjects, placebo-induced increases in ghrelin levels were more than double. Our findings support the notion that ghrelin has a role in reward mechanisms and suggest that there is a dysregulation of the ghrelin system in heavy drinkers,” the authors concluded.

The study adds to the growing evidence that ghrelin modulates the alcohol reward pathways in the brain, but it also has limitations that need to be taken into account. Notably, the group of heavy drinkers was very small and alcohol was administered intravenously. That is not how alcohol is normally consumed.

The study, “Ghrelin Predicts Stimulant and Sedative Effects of Alcohol in Heavy Drinkers”, was authored Elizabeth Ralevski, Tamas L. Horvath, Marya Shanabrough, Jenelle Newcomb, Emily Pisani, and Ismene Petrakis.

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