The Science of Nicotine Addiction - Page 2

By Jeanene Swanson 08/04/14
There are 50 million nicotine addicts in the US, and one in five deaths results from smoking. According to the CDC, smoking is still the leading preventable cause of death. Here's why it is so hard to kick, and the treatments.

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There are a variety of treatment modalities out there, and it depends on a variety of factors as to which one will work best for an individual.

  • Smoking cessation aids

These can come in many different forms, but they can be generally categorized as nicotine replacement therapy—patch, gum, lozenges, and others—and medications to help with cravings and withdrawal—bupropion (Wellbutrin) and varenicline (Chantix) are two.

The bad news is that today’s smoking cessation treatments have modest long-term success rates. In fact, research has shown that less than 25% of smokers remain abstinent a year after treatment. Scientists are looking into ways to improve upon this disheartening statistic. In a recent study published in June in the American Journal of Psychiatry, researchers found that combining two smoking cessation therapies—adding bupropion to varenicline—is more effective than using just one method, for smokers who weren’t initially helped by the nicotine patch.

“The combined treatment had a much greater effect on male smokers and those highly dependent on nicotine, while no significant difference was seen in female smokers or those with lower levels of nicotine dependence,” says Jed Rose, director of the Center for Smoking Cessation at Duke University and the study’s lead author. “One possible explanation is that male smokers have been found to have a deficit in brain receptors for dopamine, which is one of the key chemicals involved in addiction. Bupropion works in part by raising the level of dopamine signaling in the brain, and so male smokers might have derived a greater benefit when bupropion was added to varenicline treatment.”

Another recent study, published in JAMA in July, found that combining varenicline with nicotine replacement therapy was more effective than varenicline alone for abstinence at six months. However, the study showed that in the combination treatment group, there was more nausea, sleep disturbances, skin reactions, constipation, and depression; the varenicline-only group experienced more abnormal dreams and headaches.

  • Nicotine vaccine

While there is hype surrounding a vaccine for addiction, especially for cocaine and now, nicotine, NicVAX has not yet lived up to it. As a conjugate vaccine—a nicotine-based molecule linked to an antibody to nicotine—NicVAX works by binding to nicotine, effectively quarantining it in the blood, and thereby preventing it from binding to nicotinic receptors in the brain.

While early trials showed promise, two Phase III trials from 2011 failed—the vaccine worked no better than a placebo. A proof-of-concept study published in the American Journal of Psychiatry in 2013 showed that indeed, immunization led to a 12.5% reduction in nicotine binding to a specific nicotinic receptor as well as a 40% reduction in cigarette use and a significant reduction in craving for cigarettes. However, the study’s clinical validity was compromised by its small subject size and lack of control group, among other factors.

In a very recent study published in Addiction in August, scientists concluded that NicVAX “does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioral support.”

  • Treatment programs

Treatment programs, like the 12-step-based Nicotine Anonymous or inpatient courses, might work for some. The eight-day residential treatment program at the Mayo Clinic Nicotine Dependence Center in Minnesota “provides the most intensive treatment option available for stopping smoking,” according to its web site. More than 1,300 people have been treated since the program began in 1992. Two other inpatient programs are at St. Helena’s Center for Health in Deer Park, California and Hazelden’s Next Step program.

Genetic testing

Why are some smokers more addicted than others? “Addiction depends on both a genetic predisposition and experience with nicotine,” Rose says. “Similarly, both genetic factors and environment influence the ability to successfully quit smoking. Situations eliciting stress or negative mood are the main precipitants of relapse among those trying to maintain abstinence.”

Several studies show that genotyping patients before prescribing them cessation aids will work better, in other words, have better quitting outcomes. In one study, published in 2007 in the journal Nicotine & Tobacco Research, scientists conducted a randomized, double-blinded, placebo-controlled trial examining genetic influences on treatment response to sustained-release bupropion. They found that a specific genotype, or mutation, of the dopamine D2 receptor might influence treatment response to bupropion.

Not only do genetic differences influence a person becoming addicted, but there are “robust genetic influences likely for individual differences in abilities to quit,” write the authors of an article published online in 2012 in the journal Molecular Psychiatry. In this study, co-authored by Rose at Duke, the scientists were able to identify mutations that could predict the success of quitting smoking, but also that these same genetic factors influence the rate of becoming addicted (to anything) during adolescence.

Says DiFranza, “Some people are more addicted than others, some have better support systems and coping skills, and people certainly differ in how they experience nicotine withdrawal.”

Indeed, the process of quitting—or, trying to quit—is an ongoing one for John. His incentive to quit for those two years was a coughing fit behind the wheel of his car. He was fed up, but also, “I wasn’t going to let myself fail.” At the time, he was working in an office where everyone knew he was quitting. He picked up running, and that seemed to help, too. “Environment has a lot to do with it,” he says.

Jeaneane Swanson is a regular contributor to The Fix. She last wrote about the unhappy side effects of anti-depressantserasing your traumas and alcoholism and genetics.

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Jeanene Swanson is a science journalist who specializes in mental health and addiction. As a science writer with a background in biotechnology, she enjoys turning complex subjects into stories that everyone can understand—and apply to their lives. You can find Jeanene on Linkedin.