Minds Over Gray Matter
University of Minnesota researchers aim to harness the power of the brain to solve addiction.
Substance addiction is one of the biggest and most expensive challenges of our time. The federal National Institute on Drug Abuse estimates the financial cost at $700 billion per year in health care, crime and law enforcement, and lost work productivity. And addiction kills some 28,000 people every year. Scientists across a wide range of specialties at the University of Minnesota have focused their research on tackling this problem, looking to address addiction in new ways that delve into its causes and triggers.
The connection between addiction and brain research is an area that holds particular promise. We highlight the work of four researchers who have taken innovative approaches to deepening our understanding of the role that the human brain plays in addiction.
For the last several years, associate professor of neuroscience and psychology Mark Thomas has focused his work on targeting specific areas in the brain that cause addicts in recovery to relapse. Thus far his research subjects have been morphine-addicted mice, but Thomas and his colleagues are inching ever closer to being able to apply what they’ve learned to human subjects.
The goal of their research is to find ways to manually “turn off” the relapse response, perhaps through a device that provides electronic stimulation in the same way an EpiPen helps a person survive a potentially deadly allergic reaction. Because recovering addicts are so susceptible to falling off the wagon, the ability to locate the correct biomarker and shut this response down could be life changing.
Lately Thomas and his colleagues have seen significant advances in their work, earning professional acclaim and multimillion-dollar grants from the National Institutes of Health. The tool that’s allowing them to probe deeper into the brain is optogenetics: using light-sensitive proteins to alter brain function. Thomas directs pulses of light into targeted areas of the brains of his rodent subjects, disrupting relapse-like behavior.
How soon does Thomas think he’ll actually be able to help humans put an end to addiction—maybe even to addictions of the nonchemical kind, such as gambling?
“Sometimes I think we have it all here: It’s just a matter of putting the pieces together. Those are the good days. And then on the bad days, I think it is going to take some real leaps to get there. But the good news is that lately I have more good days than bad,” Thomas says.
Like Thomas, professor of psychiatry Kelvin Lim is interested in reducing the incidence of relapse, but he approaches the problem using different tools than Thomas. Using brain scans of addicted people who have been through treatment and withdrawal, Lim and his colleagues measure how much communication is occurring between their brain’s reward center and their cognitive control center. Lim has discovered that the stronger the communication between these two areas of the brain, the greater the chances of continued sobriety six months later.
Since the vast majority of addicts relapse within a year, Lim and his colleagues hope to be able to use their findings to predict which people in recovery are at higher risk of relapse. With this knowledge in hand, Lim believes that those individuals could perhaps get the focused, intense recovery help they desperately need.
Reduce reliance on opioids
Much of Carolyn Fairbanks’s research is on reducing brain exposure to highly addictive, opioid-based pain-relieving drugs. While she appreciates the important role that opioid-based drugs can play in pain relief, Fairbanks (Ph.D. ’99) also believes it is essential to develop nonaddictive pain medicines for people whose diseases are not life-threatening or who are at higher risk of addiction.
“We’re trying to find new ways to develop pharmacological treatments that target nerve endings and the spinal cord,” says Fairbanks, a professor of pharmaceutics. “This will keep these drugs as far as possible away from the brain.” Fairbanks’s work keeps her in collaboration with scientists from around the globe: “This is a national and international effort to try to find improved ways to provide pain relief so that we can reduce reliance on morphine, fentanyl, hydrocodone, and other forms of opioids.”
Another promising idea that Fairbanks is focused on is the possibility of using gene modification to reduce the body’s response to pain. This nascent idea would involve “modifying the genes of the different cell types that contribute to the pain pathway so that they would instead produce analgesic substances like endorphins,” Fairbanks explains. Her self-described “Star Trek” approach would involve engineering peripheral or spinal-cord neurons to produce signals that would halt pain impulses before they get to the brain. But Fairbanks notes that this approach, if used incorrectly, would have the potential downside of erasing the body’s ability to feel pain.
“Pain is a really important process,” she says. “We don’t want to interfere. People who don’t have natural pain systems have a lot of challenges in life.”
Keep drugs away from the brain
Like his colleague and former mentee Fairbanks, professor of neuroscience George Wilcox is also interested in keeping drugs away from the brain: restricting powerful pain-relieving medications to the spinal cord, the peripheral nerve endings, or the internal organs, so patients will experience pain relief but are less likely to become addicted.
Working with mice, Wilcox and his team have discovered a combination of two drugs that, when used together, yield greater potency than when used alone. And neither drug crosses the blood-brain barrier, thus greatly reducing the chance of addiction. This discovery means that a 99 percent reduction in dosage would give the same amount of pain relief without brain involvement. Wilcox’s ultimate goal is to apply this finding to relieving pain in humans. Human testing, he says, is just on the horizon.
“If you can reduce the number of brains exposed to these drugs, then I think we could have a win,” Wilcox says.