Originally published in MedPage Today
by Kristina Fiore, MedPage Today Staff Writer
By the end of January, many New Year’s resolutions have been tossed out with the leftover holiday cookies. That’s because change is hard — and neuroscientists are learning why.
Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain’s reward system — based largely on the neurotransmitter dopamine — thirsts for more, while inhibitory control centers experience a system failure.
The pattern is similar across all kinds of behaviors — from cocaine and tobacco addiction to overeating. That’s why changing your mind may be the first step toward breaking a habit, but altering the brain’s neural machinery is the real challenge.
Drug-taking and other addictive behaviors “hijack” the brain’s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke’s and Roosevelt Hospitals in Manhattan.
In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity — say, eating or sex — to make patients want to repeat a behavior that’s crucial to the survival of the species.
Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.
The problem arises when the memory and the craving to recapture it takes over a person’s life.
“Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they’re so closely connected, geographically and anatomically speaking, with our memories and our emotions,” Levounis says.
As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain’s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.
“Ultimately,” Levounis says, “the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.”
These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.
Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York’s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.
The scans have revealed similarities in brain activity — or a lack thereof — between patients addicted to cocaine or alcohol, and those “addicted” to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.
But in both drug-addicted and obese patients, the scans show very little red activity, because there aren’t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain’s way of coping with a constant dopamine overload.
“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.
“If they’re obese,” Wang said, “they have a problem controlling their eating behaviors.”
Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.
Out of Control
Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for MedPage Today.
Eating, to him, was a “compulsion” — as was biting his nails, a habit he picked up at age 4.
Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.
He doesn’t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn’t experiencing a placebo effect.
“I believe I was on the drug because it controlled a compulsion that I had had for 50 years,” Susman says of the nail-biting. “This stopped it cold.”
Unfortunately, he says, the same didn’t happen with his eating habits, but he’s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.
The still-investigational drug is lorcaserin — a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is “supposed to improve your willpower, your ability to overcome compulsions.”
Lorcaserin is a selective 5-HT2C receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.
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.”
Kicking the Habit
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 methadone 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.
These have been the two main strategies in addiction pharmacotherapy, but there’s now a “third avenue” — the partial agonist approach.
The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an “oomph” to calm cravings. That’s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.
But what about inhibitory control? What if medications could ramp up will power?
“It’s an area of active research,” Levounis says. “There are some medications proposed, but nothing to write home about.”
He said treatment is typically twofold. For addicts, psychiatrists will try to “cool down” the reward pathways, often with medication. Then, they target the diminished frontal lobes.
“We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,” Levounis said.
Researchers agree that psychotherapy is key to regaining self-control, and it’s the predominant treatment used in patients with addictive behaviors.
Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it’s anxiety or depression.
Acknowledging those problems may help change behaviors. Once they’re realized, a patient can start working against them, with the help of the brain’s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.
“[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,” he said. “If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.”
Smaller said it “creates a new psychological — if not neurological — structure that can help regulate behavior.”
Although research on neuroplasticity is relatively young, the concept of “rewiring” the brain is not new.
In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year’s resolution deferred: “I can’t stop eating chocolate, I’m just not wired that way.”