Food fix: neurobiology highlights similarities between obesity and drug addiction.

It was 1990, and Neal, a 55-year-old salesman from Silver Spring, Md., was hitting rock bottom. For years, he had soothed the stress of his chaotic life with an evening bowl of vanilla ice cream. But in time, that just wasn't enough. Neal started adding a second bowl, then a third. Even after he'd moved on to wolfing down an entire gallon in a single sitting, he soon needed yet a bigger fix. He added doughnuts--one, two, then an entire box.

Neal's not-so-sweet nightly habit eventually blew his weight up to 350 pounds. What he gained in size, he lost in other parts of his life: His marriage fell apart, he lost his job, and he spent his nights wondering whether his persistent chest pain meant that he'd die before morning. As his life spiraled downward, he spoke to a friend who was a recovering alcoholic.

"When he was telling me the story about what he was doing with alcohol, I could see that's what I was doing with food, how I was using it," Neal says. At the time, he says, food seemed like an innocuous fix--it was hard for him to imagine overdosing on ice cream and doughnuts. "But if it wasn't food," he adds, "then it would have been cocaine, heroin, alcohol, or something else for me."

Many people have suspected that addiction underlies much of obesity. In fact, in 1960, an overweight woman started a weight-loss group that used a 12-step program modeled after that of Alcoholics Anonymous. Neal turned to Overeaters Anonymous and has since lost more than 100 pounds. Several other groups use 12-step programs to deal with overeating.

In recent years, scientists have discovered neurological connections between overeating and drug addiction. They've conducted studies showing that the brains of individuals with either of these conditions differ from other people's brains in similar ways. The researchers have also described a few enlightening differences between the brains of overeaters and those of drug abusers.

Understanding the neurological causes of overeating and drug addiction, say the researchers, could lead to new treatments for both conditions.

FILLING A VOID Overeating and drug addiction probably come from ancient roots but have taken a modern twist, says Roy Wise of the National Institute on Drug Abuse (NIDA) in Bethesda, Md. He and others espouse the hypothesis that these problems have arisen as a by-product of the brain circuitry that motivated our ancestors to find sustenance, mates, and other necessities that enhanced the long-term success of the species.

"The brain circuitry that we use to find drugs or food has the same mechanisms involved in looking for anything rewarding," says Wise.

As humans became more adept at manipulating their material world, people recognized and later created substances that especially satisfy these reward-seeking brain circuits. A similar situation has turned up in recent history with food, says Wise: As the availability of cheap, tasty food has skyrocketed, so has the number of people who are obese as a result of overeating.

Nora Volkow, the director of NIDA, agrees. "When you hunt animals, you may succeed or not. But when you open the fridge, you will succeed 100 percent of the time" she says.

Volkow wants to know why some people can't seem to close the fridge. "Is the signal [to eat] really stronger in overeaters, or is the part of the brain controlling these urges not normal?" she asks. She and her collaborators began to answer this question in 2001, when they studied differences between the brains of normal-weight and of obese people.

In previous research that had focused solely on drug abusers, Volkow and other researchers found that many addicts had a deficiency in a particular type of receptor for dopamine, one of the brain's feel-good chemicals. Most drugs of abuse reward their takers--and reinforce the habit--by flooding the brain with more dopamine than normal. So, the researchers theorized that some drug users become addicts as a way of making up for a shortage of dopamine receptors.

Scientists have known for decades that eating also floods the brain with dopamine. When Volkow and her colleagues looked at the brains of 10 obese people, the team found a dopamine-receptor deficiency identical to that in drug addicts. Volkow stresses that obesity seems to be a significantly more complex disorder than drug abuse because many unrelated factors, such as glandular problems, lack of exercise, or a genetic predisposition to storing fat, can lead to weight gain (SN: 4/2/05, p. 216). However, the brains of several of the obese volunteers in Volkow's study seemed to be telling another story: "These people were compulsively driven to eat as if food were their stimulus of choice," she says.

CONSTANT CRAVING A more recent study sheds light on the mechanism behind cravings, whether they be for illicit drugs or specific foods.

In the past decade, many studies have sought the identity of the brain areas and chemical signals that trigger drug cravings--information that could eventually result in pharmaceuticals that help addicts stick to treatment programs. However, notes Marcia Pelchat of the Monell Chemical Senses Center in Philadelphia, hardly any neurological studies have focused on food cravings.

Pelchat and her colleagues designed a study that separated food cravings from hunger by denying people desired foods but keeping them satiated.

At the beginning of the study, the scientists asked each person to name a couple of foods that he or she "really liked." Then, the researchers gave some study subjects as many nutritionally complete vanilla shakes as they could eat, but nothing else. Other subjects could eat whatever and as much as they wanted, including the shakes.

After keeping 20 people on one of the two diets for a day and a half, Pelchat's team gave each of the subjects a functional magnetic resonance imaging (fMRI) scan, which measures brain activity. During the scan, the researchers flashed the names of the volunteers' favorite foods on a screen, alternating them with the brand name of the vanilla shakes. The study subjects were asked to imagine each food in great detail--how it looked and smelled and what it felt like to eat--and to report any cravings they were having.

Not surprisingly, the people fed only vanilla shakes reported significantly more cravings than did participants who'd had no diet restrictions. When the researchers examined the fMRI images generated by patients with food cravings, they found activation of the hippocampus, the insula, and the caudate, which are the same brain areas that other researchers had pinpointed in drug cravings and the reinforcement of addictive habits.

"This is consistent with the idea that cravings of all kinds--whether for food, drugs, or designer shoes--have common mechanisms," says Pelchat.

PURE PLEASURE With so many enticements surrounding people every day, how does someone become addicted to food rather than alcohol, drugs gambling, video games, or various other alluring pleasures? A 2002 study by Gene-Jack Wang and his colleagues at Brookhaven National Laboratory in Upton, N.Y., gave researchers food for thought.

For the study, Wang's team recruited 30 healthy volunteers--10 who were obese, the rest of normal weight. After having the volunteers fast for 16 hours, the researchers gave them a sugary solution containing a trace of a radioactive chemical. Wang and his colleagues then conducted positron-emission tomography scans on the participants. This test showed where the brain was using the sugar as fuel, a measure of brain activity.

Right away, Wang says, his team noticed a stark difference between the brain scans of many of the obese and nonobese volunteers. Specific areas of the parietal cortex, an area that takes in sensory information from the body, lit up only in the obese subjects.

Wang checked an anatomy textbook and found that the areas highlighted in the obese study participants responded to various sensations from the mouth, lips, and tongue. Studies by other researchers had shown that these areas aren't overactive in people addicted to drugs.

Wang's team hypothesizes that some obese people get more pleasure from eating than people of normal weight do. As such, "they may be more susceptible or vulnerable to some types of food," he says.

Scientists are currently investigating neurological differences between obese individuals. For example, Wang is employing an implanted device, called a gastric pacemaker, designed to make the stomach feel full. The device decreases appetite by stimulating nerves that control the digestive system. Most obese people eat less in response to this pacemaker, but some don't respond.

Wang's team hypothesizes that these people's dopamine systems and other brain areas motivating them to eat may be overriding the system that senses satiety.

WANT A NEW DRUG? As more information turns up on how drug addiction and obesity are neurologically similar, some researchers are using the findings to craft treatments aimed at both problems. The most logical target seems to be the dopamine system. However, notes Wise, chemicals that completely block dopamine are "too blunt a tool."

"If you block all dopamine, it blunts all the pleasures of life. We need to make just a small adjustment to [patients'] lives, like technicians fine-tune the ratio of fuel and oxygen in a racecar," he says.

Many researchers are therefore targeting brain systems that have some sway over the system regulated by dopamine. An experimental drug called rimonabant appears promising. It works by dampening activity in the endocannabinoid system, a brain network that indirectly hikes dopamine concentrations in the brain.

In the most recent study of rimonabant's performance, published in the April 16 Lancet, researchers tested the drug in people who were overweight or obese. They gave 1,507 volunteers various doses of the drug or a placebo for 1 year. Of the 599 people on the highest dose--20 milligrams (mg)--of rimonabant, almost 70 percent lost at least 5 percent of their body weight. Only about 50 percent of the volunteers taking a placebo lost that much weight.

In March 2004 at the American College of Cardiology Scientific Sessions in New Orleans, researchers announced positive, although modest, results in a study using rimonabant for smoking cessation. Of the people who received a 20-mg dose of the drug, about a third quit smoking within 15 days. Only about one-fifth of the placebo takers quit in the same time period.

However, another result may give hope to weight-conscious smokers. People getting 20 mg of rimonabant lost 0.5 pound, on average, according to Julissa Viana of Sanofi-Aventis, the company that makes rimonabant and sponsored the study. People who got the placebo gained about 2.4 pounds.

Wise notes that rimonabant is probably only the first of many drugs intended to fight both obesity and drug addiction. But until such drugs are available for prescription, many researchers suggest following the same tenets that have helped Neal battle his overeating for the past 15 years: Eat right, exercise, and get a little help from your friends.