"If a person constantly has an excess of dopamine, the brain will down-regulate," Wang says, explaining the principle commonly referred to as "tolerance." "Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state."
Thus, obese patients "will want to eat more in order to compensate for their down-regulated system."
In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function -- the area associated with inhibitory control.
Those studies also revealed that a higher BMI was liked to a decrease in memory and executive functioning.
"If they're obese," Wang said, "they have a problem controlling their eating behaviors."
Ed Susman was 293 pounds when he became a patient in a clinical trial of an investigational weight loss drug. He chronicled his year-long experience in a series of articles for MedPage Today.
Eating, to him, was a "compulsion" -- as was biting his nails, a habit he picked up at age four.
Over the course of the trial, not only did Susman lose 52 pounds. He also stopped chewing on his fingertips.
He doesn't yet know if he was on the drug or on a placebo. But he strongly suspects he wasn't feeling a placebo effect.
"I believe I was on the drug because it controlled a compulsion that I had for 50 years," Susman says of nail-biting. "This stopped it cold."
Unfortunately, he says, the same didn't happen for his eating habits, but he's only gained back 10 of those 52 pounds in the year he's been off the trial.
The drug was Lorcaserin -- a combination of benzazepine and hydrochloride, two neurological agents. Susman says the drug is "supposed to improve your willpower, your ability to overcome compulsions."
Lorcaserin works through the serotonin system, which regulates appetite, mood and motor behavior.
But two other investigational obesity drugs target the dopamine reward system -- Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.
"Some medications that have used similar dopamine modulation, until now, have failed," Wang said. "These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they've been very effective."
Wang called the new medications "a bright light for the treatment of obesity."
Basically, the idea of medications that act on the dopamine system is "to cool down those reward pathways," Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.
The agonist strategy is "feeding the beast, providing activity in the cell so that the cravings go down," Levounis said. Classic examples are nicotine patches, or methodone for opioid dependence.
On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won't feel anything if he or she attempts to get high.
"After a while, you say, 'This is not worth my time, my money, my trouble,' so you stop using," Levounis explains.
While these have been the two main strategies in addiction pharmacotherapy, there's now a "third avenue" -- the partial agonist approach.