Scientific Studies Support Strategies to Curb Nicotine Addiction

CHICAGO—Although the addictive nature of nicotine appears obvious, it is only in the last few years that studies have provided a scientific understanding of nicotine addiction, Alan Leshner, PhD, said at the Eleventh International Conference on Tobacco or Health. Such information provides a firm scientific basis for smoking prevention campaigns, treatment strategies, and tobacco policy development.

“The science of nicotine addiction should play a pivotal role in all tobacco control efforts, including science-based medication, behavioral therapy, and prevention approaches,” said Dr. Leshner, director, National Institute on Drug Abuse. “Science-based approaches to smoking control show we should be focusing on the people who are most vulnerable and addressing regulatory issues related to nicotine delivery, mechanisms, and use.”

Smoking control programs that target the reasons why people smoke should be built on studies of what nicotine does to the brain, he said. “We don’t have to use inexact metaphors like eggs frying on a sidewalk to show your brain on drugs,” Dr. Leshner said.

Diagnostic radiology techniques, such as functional magnetic resonance imaging (MRI), indicate that the primary sites of action of nicotine in the brain modify mood or emotional state.

One set of functional MRI scans from the Medical College of Wisconsin, Madison, confirmed what other imaging studies have revealed—the areas of the brain that are activated during nicotine use by experienced smokers relate to the normal experience of pleasure, emotional memory, and sympathomimetic function, and they include the nucleus accumbens, amygdala, and thalamus.

Physiologic changes induced by prolonged use of nicotine include an increase in the number of nicotinic receptors in the brain and long-lasting changes in the levels of monoamine oxidase A, which regulate the dopamine pathway in the brain.

Positron emission tomography (PET) scans reveal that smokers have lower monoamine oxidase A levels and therefore experience more dopamine release than do nonsmokers.

Just like other drugs that are abused—cocaine, methamphetamine, and marijuana—nicotine elicits a rapid spike in dopamine level. “We have learned over the years that people love that dopamine spike, and nicotine is like every other drug of abuse; it produces the dopamine spike right away,” Dr. Leshner said.

The reason people cannot easily stop smoking is also related to the action of nicotine in the brain. It is well established in the clinical literature that a large percentage of daily smokers (approximately 51%) progress to addiction.

In comparison with other drugs of abuse, nicotine has the highest rate of addiction: 32% of the people who use tobacco become addicted, compared with 15% of those who drink alcohol, 17% of those who use cocaine, and 23% of those who try heroin.

Findings such as these suggest that at some point in a smoker’s history, nicotine exerts a biochemical effect that transforms a voluntary drug user into an abuser. “You begin as a voluntary user, and then because of what nicotine use has done to the brain, something happens; a metaphorical switch flips, and you move from a state of voluntary drug use to a state of compulsive use,” Dr. Leshner said.

Although nicotine addiction is, at its core, a brain disease, it is also influenced by historical and environmental factors. According to scientific studies, most people who quit smoking relapse within a year. Relapse is often triggered by such factors as the need to use tobacco to relieve stress or using low doses of nicotine, or in response to drug-associated stimuli such as smoking after meals.

As a disorder that involves both biology and behavior, nicotine addiction is similar to diseases, such as hypertension, asthma, and diabetes, that require not only medical intervention but also behavioral change.

Increasing numbers of clinically tested medications have been introduced in the last decade: nicotine gum, aerosols, inhalers, and patches. Also proved effective are scientifically based behavioral therapies, including cognitive behavioral therapy, contingency management and contracts, group therapy, alternative therapy, and Internet self-help programs.

Science will continue to improve our understanding of nicotine addiction in the next few years, Dr. Leshner predicted. Neurobiologic technologies will provide insight into brain function while smokers are smoking. Molecular genetics and gene arrays will help reveal the mechanisms that underlie smoking behavior. Basic science research is beginning to show how nicotine can be prevented from entering the brain as well as how nicotine metabolism can be manipulated to treat nicotine addiction, he said.

“We are moving to far more physiological approaches in medication development based on what we have learned about the nature of nicotine and its effects on the brain,” Dr. Leshner concluded.