Sip, Sip, Puff, Puff

August 1, 2004

Even small amounts of alcohol boost the pleasurable effects of nicotine, inducing people to smoke more when drinking alcoholic beverages, according to tests conducted by Duke Medical Center researchers. The findings provide a physiological explanation for the common observation that people smoke more in bars. The research also explains statistics showing that alcoholics tend to smoke more than nonalcoholics and that smokers are more likely to be alcoholics.

The research, published in the February/March issue of Nicotine and Tobacco Research, may help elucidate why those who have quit smoking often relapse while drinking alcohol. Those insights could lead to new smoking-cessation methods that take the drugs' interaction into account, says Jed Rose, director of the Duke Nicotine Research Program and co-creator of the nicotine patch.

Such methods would be particularly useful for heavy drinkers and people with an addiction to alcohol, Rose adds. The National Institute on Alcohol Abuse and Alcoholism funded the study.

"Epidemiological, clinical, and laboratory evidence clearly indicate a behavioral link between cigarette smoking and alcohol use," Rose says. "The combined use of cigarettes and alcohol presents health risks over and above the risks posed by smoking alone, and thus constitutes a serious public-health problem that deserves additional research attention. In particular, understanding the pharmacological basis of the interaction between alcohol and nicotine could lead to the development of effective strategies for treating the drugs' dual use."

Eighty to 90 percent of alcoholics smoke--a rate three times that of the general population, Rose says. Moreover, the prevalence of alcoholism in smokers is ten times higher than among nonsmokers. Laboratory studies have revealed a similar connection, demonstrating that the rate of smoking increases substantially when people drink.

However, the physiological reasons for that increase have remained less clear, he says. One theory holds that nicotine offsets the sedative effects of alcohol. Studies have reported that nicotine counteracts the decline in the performance of certain visual tasks and the slowed reaction time induced by alcohol. Alternatively, using nicotine and alcohol in concert might serve to increase the feeling of pleasure associated with either drug alone. Both drugs have been shown to boost brain concentrations of dopamine--a nerve-cell messenger implicated in the positive reinforcement underlying addiction.

Neurobiological studies have yielded further conflicting evidence. Some have reported that ethanol increases the activity of the brain receptors that respond to nicotine, while others have indicated a dampened response of certain subtypes of the so-called nicotinic receptors in the presence of ethanol.

The Duke team recruited forty-eight regular smokers who normally drank at least four alcoholic beverages weekly. The researchers served each participant either alcoholic or placebo beverages. In one such session, individuals were provided regular cigarettes, while in another they were provided nicotine-free cigarettes as a control.

According to the participants' own ratings, ethanol enhanced many of the rewarding effects of nicotine, including satisfaction and the drug's calming effects, compared to placebo beverages. Smoking nicotine-free cigarettes did not elicit the same positive response from those receiving alcohol, the team found, indicating that nicotine itself, rather than other aspects of smoking, was the critical ingredient underlying the interaction.

"A relatively low dose of alcohol--below that required to induce any measurable euphoria--was enough to increase participants' enjoyment of nicotine significantly," Rose says. "In light of the current finding, it makes sense that so many people who have quit smoking relapse when they drink."

To further define the interaction between nicotine and alcohol, the researchers compared individuals' responses to nicotine after taking mecamylamine, a drug known to be a nicotine antagonist, to their responses after drinking alcohol. While alcohol boosted the rewarding experience of nicotine, mecamylamine had the opposite effect. Participants smoked more initially to offset the drug's action, but reported reduced satisfaction from smoking. That result further supports the idea that ethanol serves to enhance nicotine's effects, thereby encouraging their combined use, the researchers concluded.

Mecamylamine might offer a novel treatment to help smokers who also drink alcohol quit both drugs, Rose says, because mecamylamine has been found to counteract the effects of both nicotine and alcohol. "Such an approach to smoking cessation would work especially well for drinkers, as it would dampen both desires."