No Smoking

No Smoking

Each year almost 10,000 Tennesseans die as a direct result of cigarette smoking. Yet some 1.1 million of the Volunteer State’s residents over the age of 18 continue to smoke. That’s nearly 28 percent of the state’s population, compared with the national average of 23 percent.

The loss is not limited to lives alone. The Campaign for Tobacco-Free Kids reports that $1.7 billion of Tennessee’s annual healthcare costs are related to smoking. Smoking-caused productivity losses contribute an additional $2.5 billion. The effects don’t end there: smoking also is a primary gateway to illicit drug use.

Given this monumental problem, researchers at the UT Health Science Center (UTHSC) are taking on the challenge of discovering ways to prevent smoking and help people stop smoking. Scientists are approaching the task on two fronts: in basic science laboratories and in the clinical setting with smoking-cessation clinical trials. The dual healthcare initiatives are clear evidence that UTHSC’s mission–to improve the health of all Tennesseans–is a serious long-term commitment by the state’s flagship academic health science institution.

“The UT Health Science Center is a hotbed of addiction research. We’re doing research on all kinds of addictive substances: nicotine and tobacco notably, but also, inhalants, alcohol, and cocaine,” says Dr. Burt Sharp, Van Vleet Chair of Excellence and chairman of the Department of Pharmacology in the College of Medicine. With nearly $20 million dedicated to tobacco and addiction-related research on the Memphis campus alone, that comment borders on the understatement.

The two big UTHSC guns aimed at tobacco and addiction research are the Department of Pharmacology, with an arsenal of $9.65 million in National Institutes of Health (NIH) grants, and the Department of Preventive Medicine, with nearly $9.5 million, also from NIH.

Sharp says some of the most important research on the effects of nicotine on brain development and function is occurring at UT. “Our discoveries in this area have been path-finding, laying the groundwork for a wealth of research nationally,” he says. His team’s research has been funded by the NIH since 1985.

Pharmacology department studies focus on the effects of pregnant mothers’ smoking on their unborn children and the interaction between smoking and stress. “The overriding discovery is that smoking alters the molecular biology of the brain, and those changes are long lasting,” Sharp says. “Our challenge is to determine what we can do to re-engineer the brain so it’s not as dependent. We’re trying to learn how to get the brain back to normal.”

Sharp’s research is conducted on rats, but he hypothesizes that his findings could translate to humans. For example, his discoveries revealed that exposing the fetus to nicotine during pregnancy permanently changes the number of nicotinic receptors in the brain that control the motivation to take drugs.

“Nicotinic receptors are normally responsible for fine-tuning neurotransmission within the brain,” he says. He thinks adolescents whose mothers smoked during pregnancy are at higher risk of becoming chronically dependent on smoking.

Dr. Shannon Matta, associate professor in pharmacology, is working on the same problem. Matta explores the behavioral and neurochemical responses of animal offspring exposed to both nicotine and alcohol throughout gestation. “Our findings show that the developing brain becomes altered so that offspring are definitely more susceptible to using these gateway drugs in adolescence and young adulthood. These effects are significant and long-term,” she says. Studying the changes will help identify how to reduce and treat nicotine abuse.

The adolescent brain is a primary research target because most smokers take up the habit in their early teens. Also, studies indicate teens who experiment with cigarettes are more likely to become permanent smokers. In Tennessee, 14 percent of adolescents start smoking between the ages of 12 and 17, compared with 9 percent nationally. In the 18-to-25 age group of Tennesseans, almost 39 percent smoke.

Those who have tried to quit smoking and failed several times are testimony to UTHSC findings that nicotine can activate stress pathways in the brain that become permanent neurological changes. When a person tries to quit smoking, some of these changes may diminish in the short term, but the craving remains. When someone is under stress, or even anticipates stress, such as cramming for final exams or anticipating a poor performance review, smoking a cigarette is often the first thought.

Why does this happen? Several reasons, Sharp says. “External stressors can trigger the brain to crave the nicotine in cigarettes. Also, the former smoker has learned that smoking helps cope with certain stressors. Nicotine modifies the brain’s natural response to stress. It stands in the middle between the stressor and the response.

“Nicotine is also a wake-up call; it increases attention and memory performance and modifies anxiety, some of this by stimulating noradrenaline release within the brain’s own circuitry.”

Basic science, such as the work underway in the pharmacology department, lays the groundwork for clinical research. Clinical studies bring basic science to the patient, Matta says. “We can identify what has changed and provide potential new targets that can change brain function, lessen addictive behavior, and reduce craving.”

UT researchers emphasize one point: Smoking is the single most important cause of preventable illness and death in the United States today.

“When it comes to preventable causes for disease and dying, smoking is number one,” says Dr. Karen Johnson in the Department of Preventive Medicine. “Smoking beats poor diet, lack of exercise, and AIDS. But trying to kick the habit is not a hopeless battle,” she says. “We have found a number of strategies to help smokers quit, including behavioral therapy, nicotine replacement in the form of the nicotine patch, and sustained-release bupropion.

“If you do nothing else, never start smoking, and if you smoke, quit as soon as possible.”

Why Is It So Hard to Quit?

Drs. Karen Johnson and Robert Klesges, professors in the UTHSC Department of Preventive Medicine, have garnered millions of dollars in grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute. Both Johnson and Klesges are nationally recognized researchers who’ve been published in academic journals and featured in mainstream media from the Wall Street Journal to Newsweek magazine. They have five smoking cessation studies underway.

SUCCESS–Johnson has just completed this 436-person study and is analyzing the results for publication. SUCCESS looked at how the drug sibutramine could prevent weight gain while quitting smoking. When published, the results may encourage more smokers to quit without the fear of weight gain, a known roadblock to stopping the habit.

STAR–Johnson will compare the effects of using the nicotine patch alone, sustained-release bupropion alone, and using both products at the same time. The main hypothesis is that using both drugs together will be more effective than using either alone. STAR will follow all 595 recruited participants for 1 year to determine long-term smoking-cessation rates.

STEP–Klesges is recruiting smokers for this study, which will use a stepped approach by first giving smokers a nicotine patch, then adding sustained-release bupropion, and then gradually increasing the intensity of behavioral therapy to help with smoking cessation.

CHANGE–This clinical trial focuses on smokers with high blood pressure. A weight-loss program with a low-sodium diet is combined with the nicotine patch and behavioral therapy to determine if quitting smoking using this method will enable patients to stop smoking and not gain weight, which may raise their blood pressure.

LEAP–The goal is to determine if a combination of the nicotine patch and an exercise program can help overweight smokers quit smoking without gaining weight. Johnson, in collaboration with the University of Memphis and UTHSC associate professor Ken Ward, is conducting this trial.

If you want to stop smoking and need more information about smoking-cessation clinical trials, contact the UT Health Science Center Department of Preventive Medicine at 901-448-8400 or 800-916-2606.