Everyone knows that cigarettes are bad for you. Yet 45 million Americans smoke, a habit that shaves a decade off life expectancy and causes cancer as well as heart and lung diseases. Nearly 70 percent of smokers want to quit, but despite the deadly consequences, the vast majority of them fail.

Going cold turkey works for fewer than 10 percent of smokers. Even with counseling and the use of aids approved by the U.S. Food and Drug Administration, such as the nicotine patch and non-nicotine medicines, 75 percent of smokers light up again within a year. “We need better treatments because the current ones just aren’t working all that well,” says Jed Rose, director of the Duke Center for Smoking Cessation.

To create treatments that are more up to snuff, researchers are tinkering with combinations of existing drugs, looking at the role genetics plays in who gets hooked and turning to social media as a counseling platform. What’s more, a new smoking cessation medicine could be approved this year: electronic cigarettes, which have existed for a decade but only recently become the focus of efficacy trials.

The grip of addiction

Smoking at once relaxes and stimulates the body. Seconds after inhalation nicotine reaches the brain and binds to receptor molecules on nerve cells, triggering the cells to release a flood of dopamine and other neurotransmitters that washes over pleasure centers. A few more puffs increase heart rate, raising alertness. The effect does not last long, however, spurring smokers to light up again. Over time the number of nicotinic receptors increases—and the need to smoke again to reduce withdrawal symptoms such as irritability. On top of that, smoking becomes linked with everyday behavior or moods: drinking coffee or a bout of boredom, for instance, might also trigger the desire to reach for a cigarette—all making it difficult to kick the habit.

Smoking treatments help users gradually wean themselves off cigarettes or put an end to their cravings—most commonly via delivery of nicotine in patches or chewing gum. In addition, two non-nicotine drugs are available: a sustained-release form of the antidepressant bupropion reduces cravings; varenicline blocks nicotine receptors in the brain, reducing the flood of dopamine.

New research is teasing out why the seven FDA-approved medications have seen only limited success. For instance, researchers recently showed that some people are genetically predisposed to have difficulty quitting: Particular variations in a cluster of nicotinic receptor genes (CHRNA5–CHRNA3–CHRNB4) contribute to nicotine dependence and a pattern of heavy smoking. Moreover, a study of more than 1,000 smokers reported in a 2012 The American Journal of Psychiatry paper found that people with the risk genes don’t quit easily on their own whereas those lacking the risk genes are more likely to kick the habit without medications.

New research also suggests that the sexes respond differently to the drugs. Rose and colleagues have found that giving a combination of bupropion and varenicline to people who have worn a nicotine patch for a week raised the quit rate of patch users to 50.9 percent up from 19.6 percent—but only in men. “We don’t know why the effect seemed entirely confined to male smokers,” Rose says. “Bit by bit we’re starting to learn how to tailor treatment to sex, early response to nicotine patches, and genomic markers.”

New treatment hope

A reason for the limited success of nicotine treatments may be that they do not address a crucial aspect of cigarette use: the cues that prompt smoking. Electronic cigarettes have as a result become a popular alternative to lighting up for those seeking to quit. E-cig users inhale doses of vaporized nicotine from battery-powered devices that look like cigarettes. Carcinogen levels in e-cig vapor are about one thousandth that of cigarette smoke, according to a 2010 study in the Journal of Public Health Policy.

Anecdotal evidence indicates that the devices, on the market for about a decade, help smokers quit. Yet there’s little hard science to back up the claim, and the gadgets are not regulated as medicines. (In 2010 a court overturned the FDA’s effort to treat e-cigs as “drug delivery devices.”) “We just don’t know if they are as good as existing nicotine-replacement therapies,” says David Abrams, executive director of the nonprofit Schroeder Institute for Tobacco Research and Policy Studies and former director of the Office of Behavioral and Social Sciences Research at the National Institutes of Health.

That’s about to change. Two e-cig trials will report results this year. The first is a study of 300 smokers in Italy. It is a follow-up to a similar study in which 22 of 40 hard-core smokers had after six months either quit or cut cigarette consumption by more than half. Nine gave up cigarettes entirely, although six continued using e-cigs. The findings of the larger study, which are under peer review, are “in line with those reported in our small pilot study,” says lead researcher Riccardo Polosa of the University of Catania in Italy.

Interestingly, he adds, a control group of smokers who used an e-cig without nicotine also showed a significant drop in tobacco cigarette consumption—although not as great as those using the nicotine e-cig. This decline, he says, “suggests that the dependence on the cigarette is not only a matter of nicotine but also of other factors involved,” like the need to relieve stress or activities that trigger smokers to reach for a cigarette.