The “human hunger hormone,” ghrelin, is one you’re probably familiar with: It’s the one that makes your stomach grumble, eye snacks and food hungrily, and in general informs you that you need food. It’s what sends the signal to your brain that you’re starving and it’s time for a meal.
New research suggests that adjusting ghrelin levels and creating a new compound might actually double as a potential aide for alcoholics. Fatemeh Akhlaghi, a professor of pharmaceutics at the University of Rhode Island, gave self-identified alcoholic volunteers an experimental pharmaceutical compound that dulled ghrelin’s power. The volunteers reported less craving for alcohol afterward.
That’s partially due to the way ghrelin works. As it drives up the need to eat, ghrelin increases to higher levels before falling after food’s been eaten. And it seems it might also be linked to cravings for alcohol, just as it’s linked to cravings for food.
The new ghrelin-based compound “basically blunted the ghrelin receptors,” Akhlaghi told The Daily Beast. The compound proved safe for her small group of volunteers, so she is readying a large clinical trial that will include dozens of alcoholic volunteers to test it further.
Because eating and drinking have shared neural circuits in the brain, Akhlaghi is interested in whether ghrelin might spark alcohol craving the same way it breeds food cravings. She researches the ways that addictions share brain pathways, including similarities between alcohol addiction and food addiction. How and why does ghrelin make us order more French fries? And could it similarly push alcoholics to order more drinks?
Surprisingly, much is yet unknown about how ghrelin works. For example, it stimulates appetite not only in healthy people, but in obese people who are trying not to overeat, and who would not benefit from more eating. “In people of normal weight, ghrelin increases to let them know they need food, and then decreases after they eat. But in obese people, the level never goes completely down, even after they eat,” Akhlaghi explained. In previous research, “The feeling of hunger was gone for normal people, but only lessened for obese people.”
That function of ghrelin levels in overweight people can perhaps be turned on or off, and scientists are experimenting with these levels in those looking to lose weight but having difficulty doing so. Adapting ghrelin could help some people to quell their hunger signals.
Why do ghrelin levels shift up and down in normal-weight diners, but never go completely down in obese people? Intuitively, it might seem like internal bodily processes should be aiming to make us healthy, not shifting in ways that lead to poor health. This is what researchers are trying to unpack.
And there are startling things to learn. Akhlaghi explained that when volunteers in past studies have been given ghrelin intravenously, it increased their appetite for food with an intriguing result: “Injected ghrelin made both obese and normal-weight people crave fatty foods,” she said.
Which brings us back to alcohol addiction. If a new compound, perhaps in the form of a pill, could be perfected to blunt ghrelin receptors, alcohol craving could be reduced.
Past studies have shown how intravenous ghrelin administration in human volunteers resulted in a definite increase in alcohol cravings. In those with Alcohol Use Disorder, or AUD, higher concentrations of ghrelin were linked to a greater desire to drink alcohol. Akhlaghi is researching feelings of reward in the brain, to determine whether ghrelin’s unequal shifting may be involved in causing alcohol to feel rewarding to alcoholics but not to non-alcoholics—even when excessive drinking will bring nothing but trouble.
From a neurobiological perspective, ghrelin impacts both reward pathways and stress pathways, two key drivers of substance use. Alcohol-seeking behavior is coupled with the reward a drink brings and the subsequent relief from the stress of craving.
Akhlaghi points to other studies of the similarities between the neurobiology of alcohol craving and the neurobiology of appetite control. Obese people, who do not really need more calories, are getting “eat more” signals from their own ghrelin, which normal-weight people do not feel. AUD means getting “drink more” cravings—which non-alcoholics may not feel.
So ghrelin looks to scientists like an a really unfair hormone alcoholics and overweight people could happily live without. Since obesity can fuel diabetes, diabetics could do without it too.
Akhlaghi’s quest is welcome news for those fighting alcoholism, obesity, and those plagued by both. New research points to hope, rather than to intense cravings for beer, or donuts—or both.
The new compound under investigation was initially being developed to treat obesity and diabetes, and only recently did scientists see evidence that it might also be a fruitful research area for AUD.
Akhlaghi pointed out advantages a new compound might have over current treatments. “The drugs that are available to treat alcohol use disorder either came from opioids or other drugs that make you have an aversive effect if you drink, and each of them has only small effects,” she said.
Antabuse, a common AUD treatment, causes severe symptoms if it’s mixed with alcohol, including loss of blood pressure and vomiting. And despite such traumatic reactions, it does not work for everyone.
National Institute on Alcohol Abuse and Alcoholism data show at least 16 million people in the U.S. have AUD. This includes an estimated 623,000 adolescents ages 12–17.
“However severe the problem may seem, most people with AUD can benefit from treatment,” according to the NIAA. “Unfortunately, less than 10 percent of them receive any treatment. Ultimately, receiving treatment can improve an individual’s chances of success in overcoming AUD.”
Clearly a pill that thwarts alcoholism would be a momentous cultural event. Akhlaghi urges caution, though: “We are looking at the effect of the compound. We cannot say this is a cure; we can say it is a promising therapy.”