Brain imaging studies examine how anti-smoking medications may curb cravings

The smoking cessation medications bupropion and varenicline may both be associated with changes in the way the brain reacts to smoking cues, making it easier for patients to resist cravings, according to two reports posted online today that will appear in the May print issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

"Environmental cues associated with nicotine reinforcement induce cigarette craving, which propagates smoking habits in smokers and relapse in abstinent individuals," the authors write as background information in one of the articles. "Human brain imaging studies using functional magnetic resonance imaging (fMRI) and positron emission tomography scanning have provided insight into brain regions associated with cue-induced cigarette craving. Nicotine-dependent smokers exhibit activation in brain regions related to attention (prefrontal cortex), emotion (amygdala), reward (ventral tegmental area) and motivation (striatum) while viewing cigarette-related cues."

Bupropion, originally marketed as an antidepressant, was found to enhance smoking cessation in patients with depression and is now one of the most common therapies for smoking cessation in the world. It is known to reduce cravings in response to smoking cues, but its mechanism for doing so is not well understood. In one study, Christopher S. Culbertson, Ph.D., of University of California, Los Angeles, and colleagues assessed changes in brain activation in response to smoking cues among 30 smokers who were randomly assigned to take either bupropion or placebo for eight weeks.

Participants underwent fMRI scans within one week of joining the study and again at the end of the eight-week treatment period. During the scans, they were shown 45-second videos that contained either smoking cues-actors and actresses smoking in a variety of settings-or neutral cues, with similar settings but no smoking behaviors. Participants also used a response box with five buttons on it to report how strongly they craved cigarettes immediately after watching each video.

Patients who were treated with bupropion reported less craving in response to smoking cues than did patients who received placebo. Those taking bupropion also showed reduced activation in areas of the brain known to be associated with cravings, including limbic and prefrontal regions. Among all the participants, regardless of treatment, reports of cravings aligned with fMRI images-that is, those who showed reduced activation in craving-related areas also reported feeling fewer cravings.

"These results demonstrate that treatment with bupropion is associated with an improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions," the authors conclude.

In another article, Teresa Franklin, Ph.D., of University of Pennsylvania, Philadelphia, and colleagues studied brain responses to varenicline, a first-line smoking cessation medication. Varenicline reduces withdrawal symptoms and the reinforcement received from nicotine while smoking. The researchers studied whether it would also aid in reducing brain and craving responses when smokers are exposed to smoking cues. They used a neuroimaging technique called perfusion fMRI, which allows the measurement of longitudinal changes induced by a medication during smoking cue exposure and also in the brain in the resting condition.