Alcohol boosts the pleasurable effects of nicotine

In tests on human volunteers, Duke University Medical Center researchers have found that even small amounts of alcohol boost the pleasurable effects of nicotine, inducing people to smoke more when drinking alcoholic beverages. The findings provide a physiological explanation for the common observation that people smoke more in bars. The findings also explain statistics showing that alcoholics tend to smoke more than non-alcoholics, and that smokers are more likely to be alcoholics.

The finding, published in the February/March 2004 issue of Nicotine and Tobacco Research, might help elucidate why those who have quit smoking often relapse while drinking alcohol. Such insights might lead to new smoking cessation methods that take the drugs' interaction into account, said Jed Rose, Ph.D., 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 added. 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 said. "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 which 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, he said. Moreover, the prevalence of alcoholism in smokers is 10 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, Rose said.

One theory holds that nicotine offsets the sedative effects of alcohol. For example, 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 48 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 said. "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 that indicated after alcohol use. 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 rather than antagonize 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 as mecamylamine has been found to counteract the effects of both nicotine and alcohol, said Rose. "Such an approach to smoking cessation would work especially well for drinkers as it would dampen both desires," he said.

Collaborators on the study include Frederique M. Behm and Matthew Cramblett, of Duke; Lisa H. Brauer, Ph.D., of the University of Minnesota; Kevin Calkins, of the University of North Carolina, Chapel Hill; and Dawn Lawhon, of the University of Michigan.