Compassion + Science: Addiction research at Penn State College of Medicine

66769 LE 2By Heidi Lynn Russell

The conversation always starts the same way: “My son…” “My daughter…” “My grandchild…. has a drug problem.”

And for years, researchers at Penn State College of Medicine have been trying to solve a yearning question from people whose hearts are breaking:

“Why can’t they stop?”

But research now underway may finally unveil an answer – and some hope. Behind all of the science that goes on in sterile campus laboratories – behind the studies of rats and brain cells and clinical findings – is an understanding that many people, including those struggling with drug use, don’t always see:  Addiction to opioids alters a person’s brain chemistry, robbing them of the ability to make free-will decisions, says Dr. Sue Grigson, professor of neural and behavioral sciences.

Knowing this may allow clinicians, doctors, therapists and even family members to re-tool treatment options so that people with addictions can break a life-ending cycle. Pennsylvania, which is in the midst of an opioid epidemic, needs new treatment options now more than ever, Grigson says.

“We’re very concerned about the opioid epidemic. We’re losing 10 people a day in Pennsylvania to drug overdose.  And it’s expected that number will increase to 13 within the next year or two,” Grigson says.

Researchers will present study findings at the Third Annual Penn State Addiction Symposium on April 4, hosted by the Penn State Addiction Center for Translation (PS ACT) and supported by a grant from the Penn State Neuroscience Institute. About 140 physicians, scientists, students, post-doctoral fellows, directors from neighboring treatment centers and community members are expected to attend. Grigson is the symposium chair and also director of PS ACT.

“A Sense of Urgency”

Because of the alarming opioid overdose rate, Penn State researchers are working hard to understand differences between individuals, such as what makes them vulnerable or resilient to the effects of opioids and what happens to the brain with use, Grigson says. The university is working with five others to study opioid addiction specifically.

“With 10 people dying every day in Pennsylvania alone, we would welcome any support, from writing grants to receiving help from philanthropic groups. The more funds we have, the faster we can work. More funds mean more study. I feel a sense of urgency with the losses,” she says.

In a society that judges people for addiction, it’s also critical that everyone from therapists to law enforcement officials understand the science behind the behavior, Grigson says. For example, many assume that an opioid addiction starts with illegal activity. However, 80 percent of people who use heroin begin with a treatment for pain – something their own doctors may have prescribed post-surgery or to treat a chronic condition, Grigson says. “That point is critical,” she says. “And up to a quarter of individuals treated for pain with opioids develop problematic use – a quarter. That’s a high number.”

Dr. Nora Volkow, director of the National Institute on Drug Abuse at the National Institutes of Health, is sending a deputy director, Dr. Wilson Compton, to deliver the keynote address. Events like this symposium allow researchers to chip away at the stigma of addiction, she says.

“Just proclaiming that addiction is a chronic brain disease will not help anybody, just as telling a mother with a very sick child that her daughter has diabetes, which is a chronic disease of the pancreas, will sound similarly abstract to her,” Volkow says. “The concept begins to become more helpful when you delve into the details and explain that the cells in the pancreas can no longer produce insulin, which is a hormone that we all need to be able to use glucose as an energy source — so without it, the cells in our body are energy-deprived. Now the mother understands why her child is so sick. This symposium is part of our efforts to do the same thing for addiction.”

Hijacking “Free Will”

Volkow, Grigson and others say their research interests began with a common question: How and why do drugs take over the process of what is known as, “free will?”

“I don’t know of any other situation where an individual will give up their family, their profession or their money because of an addiction they cannot control,” Volkow says. “I wanted to know what drugs do to the brain with the hope that the knowledge we glean from such studies could one day help those whose lives have been ravaged by the devastating effects of addictive drugs.”

Dr. Kent Vrana, chair of the Department of Pharmacology, and Ashley McFalls, research assistant, have been delving into why someone, who is sober for a year or more in prison, would start using again within hours of release.

“We think drugs hijack the normal system and create changes that tell you, ‘My new normal is having a drug on board.’ So when you’re not taking drugs, these brain changes send a subliminal message that things aren’t normal,” Vrana explains. “Those changes can survive many years after they have been sober.”

To find a solution for people who want to remain in recovery, McFalls has been working with rats. After they have been taking heroin, they are put into “rehab” for two weeks. She studies the brains of those who work hard afterwards to obtain the drug. She examines selected brain regions that regulate memory, learning and reward. The remarkable thing is that the drug has changed those brain regions.

To reverse these changes, McFalls injects another drug into the brain and studies whether behavior returns to normal.

“What we reveal is that when she interferes with a brain, she can disrupt the seeking of heroin after the absence from the drug,” Vrana says. “It gives us insight into how we might support those in recovery and help them avoid relapse.”

Vrana and McFalls say they hope the findings will lead to solving an ongoing relapse issue among people who are trying to start over.

“It’s clearly our biggest problem. We can help opioid-dependent individuals to recognize they have a problem. Around 50 to 60 percent, however, will relapse. We end up with a huge problem in society,” Vrana says.

Predicting the Relapse

Suppose you tell your doctor, “My blood pressure is great. My cholesterol is fine because I’m watching my diet.” Not surprisingly, the doctor doesn’t take your word for it. Your blood pressure will be taken and lipid levels checked with a blood test. In the field of medicine, objective measures are the best source for accurate information. Unfortunately, no such objective measure exists in addiction medicine or psychiatry in general. Currently, there are no objective measures to help clinicians make informed decisions about patients individuals who insist they’re ready to leave a treatment facility, says Dr. Scott Bunce, Ph.D., associate professor of psychiatry and clinical psychologist.

“We’ve been able to safely withdraw people from substances of abuse since the 1980’s. The real problem lies in the weeks after residential treatment when they go back to their homes and neighborhoods and have a high possibility of relapsing,” he says.

What if an objective medical test could be developed like use of a blood pressure cuff, where a therapist or psychiatrist wouldn’t have to rely only on the patient’s word or good behavior? What if you could predict with a very high degree of accuracy the probability that a patient might relapse within 90 days after leaving residential treatment for a substance use disorder?  Bunce and his team are developing an objective, brain-based measure of relapse risk in patients with prescription opiate or alcohol use disorders. Bunce uses functional near-infrared spectroscopy, a neuroimaging technology that uses light to measure activation in the brain’s outer cortex.

This technology can be used to measure how a patient’s brain responds to various images and during specific tasks. Comparing the responses of patients who relapse during the first three months following residential treatment to those who remain abstinent, Bunce and colleagues are able to identify a pattern of brain responses that puts people at increased risk of relapse. Increased responses to images depicting prescription pills or alcohol, decreased responses to images depicting “natural rewards” (think ice cream sundae or a cute puppy), coupled with a decreased capacity to regulate their impulses, suggests a greater risk for relapse.

Bunce spent about 10 years developing various elements of the system he uses. He feels it could mean the difference between life and death for some people.

“One participant in our study, a patient with alcohol use disorder, was very motivated and diligent in the way he worked his program, Bunce recalls. “The staff all felt that he would do well when he left to go home after completing 28 days of treatment.  Two months later, his brother called to let the clinic know he had died of alcohol poisoning. When we went back and looked at how his brain was responding compared to his subjective measures two different stories emerged.  When he was viewing the alcohol cues, he reported his craving was zero, but data from his brain’s response during the tasks were among the highest of those participants who had relapsed in the 90 days after leaving treatment, suggesting that he was at high risk for relapse.

“The clinicians couldn’t see it. He showed a lot of cooperation and personally felt he was doing well, but the objective measure suggested he was at high risk. With this technology we can tell a person, ‘Look, your brain responses suggest you’re not ready yet.’” This development could also help with third-party insurance decisions on who gets to stay in treatment and who is healthy enough to go home. “It’s rare that anyone gets more than 28 days of residential treatment, and it’s based on very little scientific evidence of which, none is objective,” Bunce says.

Newborns: The Most Innocent Exposed to Opioids

Aside from measuring an adult’s capacity to make decisions about drugs or relapse, there is another vulnerable group at risk who sometimes go unnoticed: Newborns exposed to opioids during pregnancy.

Dr. Christiana N. Oji-Mmuo, an assistant professor of pediatrics, has been studying how hospitals can determine when a newborn suffering from opioid withdrawal is ready to go home.

“When they’re born, it takes 24 to 48 hours for withdrawal of the opioid. Their symptoms show that they are really suffering. Treatment involves soothing measurers, like pacifiers. But there is still a significant number who have to be treated with opioids for weeks to help with the withdrawal symptoms before they go home,” Oji-Mmuo says.

To assess the babies objectively, Oji-Mmuo is using a non-invasive tool which is similar to a lie detector. It measures sweat on the babies’ palms and feet. She tests them before the withdrawal, then during the withdrawal and then weekly before they go home. The tool also monitors pain in babies.

“We check out response to stimuli, like the ringing of a bell for three seconds and response to getting a heel stick. Babies who require treatment have a higher skin conductance response,” she says. Skin conductance response happens momentarily when a stimulus causes to the skin conduct electricity better than it usually does.  Babies who have lower skin responses can potentially be released to home sooner if the results of this study holds true.

Holistic Treatment

 Meanwhile, researchers at the College of Medicine hope future treatment for addiction will evolve into a combination of compassion and science. Although they may not see their research implemented in clinical settings soon, they want to shine a light on how and why people struggle. The symposium on April 4 will inform state officials, prison workers, law enforcement and other decision makers on how challenges are rooted in brain chemistry itself, they say.

“We want to treat them holistically,” Vrana says. “Folks are making bad decisions, but at the same time, their brains have been changed – they have a disease. We have to understand that throwing them in jail and throwing them back into the same neighborhood after jail does no good. From our experiments in animals, if you provide the cues that the drug is available, they’ll go crazy trying to get it. We are trying to attack it from the pre-clinical side. We’re trying to understand the underlying brain wiring to help design a better solution.”

The solutions are as complex as the problem itself, Volkow says.

“In the short term, I hope that this research will allow us to better understand the impact of drug use on brain function so we are in a better position to identify therapeutic targets or strategies and predict who’s at higher risk so we can better protect them,” she says. “This hope is anchored in my strong conviction that the better the knowledge the better prevention and treatment interventions we’ll be able to develop. And, in the long term, I believe that this research will contribute to the demise of the still pervasive stigma that makes an already challenging recovery process even more of an uphill battle.”

For more information on the Third Annual Penn State Addiction Symposium, visit the College of Medicine Web site. 



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