Penn researchers use MRI to study drug addiction

ALEJANDRO A. ALVAREZ / STAFF PHOTOGRAPHER Matthew Ellis , 25, starting using drugs as a teenager. After participating in the Penn study, he's been clean for three months.
Posted: January 18, 2013

MATTHEW ELLIS started popping painkillers as a teenager and switched to heroin a few years later. It was simple economics, and a common progression among today's opiate addicts - the recreational drug dabbler turned full-time junkie.

That's usually when the nightmare takes hold. You start living life one injection at a time. Everything else - career, family, self-respect - is prioritized behind the next little wax-paper bag of dope.

"I was hopelessly addicted to heroin," said Ellis, 25, a carpenter's assistant and father of two young boys.

Ellis, who lives in Deptford, N.J., repeatedly tried to get clean. He attempted to taper off his habit with Suboxone. He also did about seven rounds of treatment, both outpatient and inpatient. Some of his stints lasted months. But the drug seemed to stalk him from within.

"It would get in my head and stay in my head until I did it," Ellis said.

Today, after enrolling in a clinical study at the University of Pennsylvania, Ellis has three months of heroin-free time under his belt. Neuroscientists at the university's Center for Studies of Addiction are using MRI research to understand how opiates hijacked the reward system in Ellis' brain.

By watching how regions of the brain react to drug-related photos, or cues, researchers believe they can predict which addicts will succeed with certain treatments and which will relapse - a hypothesis that shatters the stubborn misconception that conquering addiction is solely a matter of "willpower."

"You can be a fortuneteller," said Anna Rose Childress, a psychologist who directs the center's cocaine-related MRI research. "But it's not just knowledge. It's not just pretty brain pictures. It's hope."

The goal is to use the research to develop more effective treatments and, perhaps eventually, personalized medicine tailored to each addict's mental strengths and vulnerabilities, which are shaped by genetics, life experiences and drug use.

They are trying, in other words, to find a cure for addiction.

"We're interested in seeing if, among the people that do better, their brains are different now," said Teresa Franklin, a neuroscientist who directs the nicotine and marijuana MRI studies at Penn.

It's crucial research in the U.S., where nearly 22 million people need treatment for drug or alcohol dependency, and where policymakers have been slow to respond to the emerging science about addiction. In America's so-called "war on drugs," think of these neuroscientists as the CIA. They're gathering intelligence about the enemy that could be invaluable down the road.

"This is not something that gets better in 12 weeks of treatment. This is a lifelong process where the brain has to be retrained," said Franklin, who lost her brother to drugs in the 1990s. "Just as if you have diabetes or high blood pressure or a heart condition, you have to change your lifestyle and you may need medication."

Free will vs. biology

"Addiction is a disease."

You may have heard the phrase, but what does it mean? Maybe you think it's an excuse. Maybe you or a relative has managed to quit drugs or alcohol without treatment, and you figure anyone can do it just as easily.

Penn's addiction experts would beg to differ. Yes, a substance abuser must actively resist the urge to keep using. And, of course, he or she must want to stop. But willpower and desire are usually two of several parts of the equation.

"It's very much, at the root, biological," Childress said.

For one drug or alcohol user, changing behavior could be as easy as stopping a new car on a flat road. For others, it could be as difficult as stopping an 18-wheeler with failing breaks from barreling down a steep hill. The level of addiction can vary widely, as can the mental tools a person has to combat it, Childress said.

"Some people may have different equipment. In the lab, we call it 'frontal endowment,' " Childress said of participants whose brains are best equipped to control impulses.

Childress said the struggle can be traced to the interplay between two regions of the brain - the ancient "go" system deep within the brain that drives the motivation for rewards and survival, and the "stop" system toward the front of the brain that deals in consequences.

"The 'stop' system is always playing catch-up," Childress said.

At Penn, neuroscientists are studying how addicts' brains respond to cues, like a heroin needle or crushed pill, to see if they can predict how addicts will fare with a particular course of treatment.

"Our hypothesis is if their frontal 'stop' regions are not working very well and aren't communicating very well with regions of the brain that say, 'Go, go, go' - for whatever: sex, food, drugs - that those are the people who are going to do poorly in treatment," Franklin said.

Brain scans show that an addict's reward system will light up even in response to subliminal drug cues. One such cue used in the study is an image of crack rocks that flashes on-screen for a few milliseconds while the addict is viewing a photo of a neutral object, such as a stapler. The addicts cannot consciously see the drugs because they flashed before them far too quickly - all they report seeing is the stapler - but parts of the brain were already reacting as if they'd consciously seen the crack rocks, Franklin said.

"If we can manipulate that response with medication or behavioral therapy, that's our goal," Franklin said.

Overcoming withdrawal symptoms is also a hurdle for addicts, but Penn's research has shown that the brain can tell a person to pursue a substance even when it's not "needed." Some cigarette smokers' brains responded strongly to smoking-related cues even immediately after they had smoked a cigarette and their body was not craving nicotine.

"Unfortunately, a lot of people think after withdrawal you're home free, but that's not the case," Franklin said. "The brain has other mechanisms."

Robert Lindsey, president and chief executive officer of the National Council on Alcoholism and Drug Dependence, said the Penn research is "incredibly important" in correcting the public's understanding of addiction and reforming failed criminal-justice policies.

"It's a chronic, progressive, fatal if untreated, and genetically predisposed illness," Lindsey said of addiction. "It's biochemical, plain and simple. But, just like diabetes and heart disease and other illnesses, there is personal responsibility for recovery."

Medication-assisted therapy

Ellis, the recovering heroin addict participating in the Penn study, was put on Vivitrol, which blocks the effects of heroin by binding to opioid receptors in the brain. Daniel Langleben, the psychiatrist directing the prescription painkiller- and heroin-related MRI research, said Vivitrol appears to reduce cravings, as well.

"It looks like the brain response of the addicted person is changing during this treatment," Langleben said. "After about a month and a half, many of our research subjects begin to become indifferent to the drug cues. They start reporting a lack of craving when they see the images."

For Ellis, that has made all the difference. Instead of being consumed by thoughts of finding heroin, he said he'll occasionally think of it, but finds it much easier to get out of his mind.

"It works," he said of Vivitrol. "I'm really surprised. I think they should open a bunch of Vivitrol clinics instead of methadone clinics."

Franklin is also experimenting with the use of the muscle relaxer Baclofen to reduce the cravings among cigarette and marijuana smokers. The results have been promising.

"It's amazing," Franklin said. "I can give somebody a dose of Baclofen and watch their reward systems just calm right down."

Franklin said the team's research could potentially be applicable to controlling other compulsive behaviors, such as gambling and overeating. If medication is needed to fight addiction, then so be it, she said.

"Some people, so far, we haven't been able to help. They don't even come to our center - They end up dead. My brother was one of those. He would never go for treatment," Franklin said. "One of the reasons people don't go for treatment is they don't believe it works. We need to get stuff out there that does work.

"But people have to want it," she added. "They really have to want treatment."

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