DURHAM, N.C. – 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.