The connection between naltrexone and food cravings is related to the way nicotine activates the brain’s opioid system.
The connection between naltrexone and food cravings is related to the way nicotine activates the brain’s opioid system. Credit: Creative Commons/Mike Mozart

New research from the University of Minnesota-Duluth demonstrates a clear connection between nicotine withdrawal and the desire to consume high-fat, high-calorie “junk foods” that can lead to weight gain. 

The research team, led by principal investigator Mustafa al’Absi, a licensed psychologist and professor in the department of Family Medicine and Biobehavioral Health, noted a connection between the opioid system, or the part of the brain responsible for addiction and appetite regulation, as a possible cause for smokers’ cravings for energy-dense, high-calorie foods during nicotine withdrawal. 

“We have direct experience through data results research that some people, when they quit smoking, start indulging in eating behaviors that may cause them to gain weight,” al’Absi said. “Cravings can get people to try to replace nicotine or cigarettes with food.” 

Those cravings — and concern that they will lead to weight gain — can make some smokers reluctant to give up cigarettes, al’Absi said. “That weight gain then can make them feel bad about having quit or nervous about the prospect of quitting. They think, ‘I am going to put more weight on than I like.’”

With a desire to understand more about the brain mechanisms that lead people going through nicotine withdrawal to crave certain foods, al’Absi and his team of researchers conducted a study of smokers and non-smokers between the ages of 17 and 75. Participants took part in two in-person lab sessions. All were randomly selected for a 24-hour withdrawal from tobacco products and then administered either a placebo or 50 mg of naltrexone, a medication commonly used to reduce cravings and feelings of euphoria for people with substance use disorder. 

The researchers then met with the study subjects, and asked them to perform a set of challenging tasks. Afterward, al’Absi said, “We collected subjective information about how they felt. We also collected physiological and hormonal measures to understand the physical impact of withdrawal and the stress it creates.”  

After about three or four hours of testing, participants were offered a tray of snacks, some high in calories, fat and salt, some with healthier characteristics. “We gave them a specific amount of time to have as much as they felt like from that tray,” al’Absi explained. 

Mustafa al’Absi
[image_caption]Mustafa al’Absi[/image_caption]
What al’Absi and his team learned was that subjects undergoing nicotine withdrawal consumed more calories than non-smoking subjects. “They chose the items that are often considered to be comforting foods, with high sweet and high fat  content,” he said. 

Like the non-smokers in the study group, participants who were smokers but had taken naltrexone were less likely to consume high-fat, high-calorie foods than smokers who had been given the placebo. 

This discovery is a new finding, al’Absi said. There is little clinical research on the impact of drugs like naltrexone on appetite, and even less on their impact on nicotine withdrawal:  “It is novel. It is still experimental — though it is more exact and accurate because it was done under our observation in a structured environment.”  

Opioid connection 

The connection between naltrexone and food cravings is related to the way nicotine activates the brain’s opioid system, al’Absi said. The opioid system helps with pain tolerance and is responsible for pleasurable feelings, so when subjects are given a medication that blocks those impulses, their cravings for comfort food go down: “Basically that medication reduced subjects’ intake of the high-sweet and high-fat items.” 

The drug that was given to his study’s subjects, al’Absi explained, “is similar to the medication that people are given in recovery from alcohol addiction. It is given to them as a way to suppress or manage their cravings.” 

This part of his research is still in the early stages; for the work to move into the clinical realm, al’Absi said that his team would have to give subjects the medication over an extended time.  “We’d need to observe behavior to see if it resulted in changing weight.” 

There is established research literature on tobacco’s impact on senses like taste and smell.  “As people stop smoking, their taste buds, their sense of smell improves,” al’Absi said. “They become more aware of the smell of food and food tastes better.” 

That at times leads to overindulgence: When combined with the physical and psychological stress of unmedicated withdrawal, the desire to eat unhealthy foods can feel uncontrollable. 

Such connections make this new line of research seem, “tantalizing,” al’Absi said. “Results suggest that we should try to think of interventions to correct these kinds of unhealthy diet choices and move more toward diets that are high in vitamins and minerals.” 

Short of medication, some of that behavioral redirection could come in the form of direct counseling and advice provided by researchers during the course of the study, al’Absi said.  “We hope if people start taking advantage of these interventions in the process of quitting tobacco, we might see some changes that could lead to healthier behavioral choices. We don’t usually emphasize things related to diet or exercise when people quit smoking.” 

Taking advantage of this period in the quitting process may be key to establishing behaviors that could improve participants’ overall health, he said. “We call this a ‘teachable moment,’ when they may be willing to engage in other positive behaviors, like ‘Pay attention to what you eat. Engage in this list of activities.’”  

For those smokers who still need extra help to quit, al’Absi said he hopes that opioid-blocking medications like naltrexone will one day be considered a useful pharmacological aid: “In certain groups it may be helpful and wise. The research is ongoing” 

Still seeking subjects

The first part of the research team’s work was conducted before the pandemic, when volunteers and researchers could easily meet in person for the extended period of time required to take samples, do testing and observe behavior. The work continues, with the research team now focusing on the impact of appetite change and weight gain post smoking cessation and the extent to which these changes increase the risk of relapse. 

COVID has forced the group to adjust their research methods. Instead of spending time with the team in the lab, subjects now do their part remotely, using Zoom to meet with researchers, complete tasks and answer questions.

“We have had to adjust a lot of things,” al’Absi said. “We can do the medication remotely. We send medications to people in a sealed envelope and they open it in front of the camera.” 

Other parts of the research are also done on camera over an extended period of time, he added:  “We are trying to approximate as much as possible what will happen in the clinic.”  

The team is actively recruiting study participants. To qualify, participants must be Minnesota residents who are cigarette smokers interested in quitting. They also must be 18 years old or older and generally healthy with access to a computer. Because the study involves multiple remote visits that take about 3-4 hours each, al’Absi said that it is important for subjects to have a room or space that is quiet and away from distraction. Compensation is provided for participation. This online screening offers more information.

Leave a comment