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Smoking, gender, hormones and the brain

Institution: University of California, Los Angeles
Investigator(s): Eran Zaidel, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8IT-0112 Award: $69,084
Subject Area: Nicotine Dependence
Award Type: Inno Dev & Exp Awards (IDEAS)

Initial Award Abstract
Despite steady progress in the fight against nicotine addiction over the past 25 years, the percentage of female smokers is increasing. The United States may soon become the first society in history in which more women than men smoke. In part, this is because women are less likely to be able to quit, whether they try on their own or with the help of smoking cessation programs. This appears to be especially true for nicotine replacement therapies (such as nicotine patches or gum), which have helped a greater percentage of men than women in almost every study. There is thus a clear need for new forms of treatment which are tailored especially for women.

Nicotine is an addictive drug, and the primary reason people use cigarettes is to get nicotine. However, other aspects such as the taste of smoke also become pleasurable to the smoker. These other aspects may be more important for women, and this could be one reason that nicotine in the patch and gum may be less likely to help them give up cigarettes. To test this theory, we will study the differences in men and women's reaction to nicotine alone, or to smoking a cigarette which contains very little nicotine.

Smokers often feel that cigarettes help them stay focused, and one of the symptoms of nicotine withdrawal is difficulty paying attention. In women, withdrawal symptoms and attentional ability may change at different points of the menstrual cycle. Our research will use a measure of attention to study the effect of smoking and withdrawal across the menstrual cycle. Our test is also able to determine differences between the right and left sides of the brain, and the effectiveness of the connections between the two sides. This is useful since gender, menstrual hormones, and withdrawal may be associated with changes in right/left balance.

The brain controls smoking, as it does any other behavior. Knowledge of which brain areas are responsible will let new treatments to help smokers quit become more effective, by specifically targeting those areas. Our research will help provide this knowledge, with special emphasis on factors (attention, menstrual cycle, and right/left brain function) that are believed to be important to female smokers.

Final Report
In our project "Gender, Smoking, Hormones, and the Brain," we have explored the ways that withdrawal from cigarettes may cause smokers to have problems with attention and with other cognitive abilities. We theorized that these effects of withdrawal may be different for the left and right sides of the brain, and attempted to determine whether cigarettes relieve these withdrawal effects by delivering nicotine, or simply by being pleasurable for the smoker. We also noted that nicotine replacement therapy is sometimes found to be more effective for men than women, and sought to determine whether this is related to sex differences in the brain which might interact with smoking.

The completed study used computerized behavioral tests and magnetic resonance imaging to demonstrate that withdrawal reduces the ability of the left side of the brain, but not the right, to focus attention away from a distracting word. We also found that withdrawal eliminates a potentially beneficial difference in the way men and women use the left sides of their brain for language, a differenceis seen in smokers only when they are smoking. And we found evidence that these effects on the left brain are primarily due to nicotine, although this did not relate to sex differences in the way we had expected.

One reason that smokers fail to quit may be that they are bothered by their inability to concentrate during withdrawal. By identifying specific regions in the brain where these problems may arise, we hope to assist the development of treatments. The work made possible by this IDEA grant will help us launch our next steps of observing changes in the left and right sides of the brain past the initial withdrawal from cigarettes and throughout the process of different therapies to help smokers quit: