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

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

"Environmental cues associated with nicotine reinforcement inducecigarette craving, which propagates smoking habits in smokers andrelapse in abstinent individuals," the authors write as backgroundinformation in one of the articles. "Human brain imaging studies usingfunctional magnetic resonance imaging (fMRI) and positron emissiontomography scanning have provided insight into brain regions associatedwith cue-induced cigarette craving. Nicotine-dependent smokers exhibitactivation 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 toenhance smoking cessation in patients with depression and is now one ofthe most common therapies for smoking cessation in the world. It isknown to reduce cravings in response to smoking cues, but its mechanismfor doing so is not well understood. In one study, Christopher S.Culbertson, Ph.D., of University of California, Los Angeles, andcolleagues assessed changes in brain activation in response to smokingcues among 30 smokers who were randomly assigned to take eitherbupropion or placebo for eight weeks.

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

Patients who were treated with bupropion reported less craving inresponse to smoking cues than did patients who received placebo. Thosetaking bupropion also showed reduced activation in areas of the brainknown to be associated with cravings, including limbic and prefrontalregions. Among all the participants, regardless of treatment, reports ofcravings aligned with fMRI images-that is, those who showed reducedactivation in craving-related areas also reported feeling fewercravings.

"These results demonstrate that treatment with bupropion is associatedwith an improved ability to resist cue-induced craving and a reductionin cue-induced activation of limbic and prefrontal brain regions," theauthors conclude.

In another article, Teresa Franklin, Ph.D., of University ofPennsylvania, Philadelphia, and colleagues studied brain responses tovarenicline, a first-line smoking cessation medication. Vareniclinereduces withdrawal symptoms and the reinforcement received from nicotinewhile smoking. The researchers studied whether it would also aid inreducing brain and craving responses when smokers are exposed to smokingcues. They used a neuroimaging technique called perfusion fMRI, whichallows the measurement of longitudinal changes induced by a medicationduring smoking cue exposure and also in the brain in the restingcondition.

Twenty-two smokers received either varenicline or placebo in athree-week randomized medication regimen. The brains of smokers wereimaged before and after the medication regimen, while 'at rest' andwhile viewing 10-minute video clips that contained either smoking cuesor non-smoking cues, and they also reported their cravings. Smokers werestill smoking during the medication regimen to explicitly examinevarenicline effects on cue reactivity independent of withdrawal, whichalso affects brain activity.

In scans performed before the medication regimen, smoking cues activatedbrain areas involved in drug-motivation, such as the ventral striatumand medial orbitofrontal cortex, and also elicited reports of craving.After the medication regimen, similar patterns of activity persisted inpatients who had taken placebo, whereas those who received vareniclineexperienced a reduction in brain activity in those regions and inself-reported craving.

In participants who took varenicline, brain activity in the restingcondition was selectivity increased in a region known as the lateralorbitofrontal cortex, which is implicated in inhibiting behavior thatpredicts reward (such as smoking cues). Importantly, increasedactivation in this area predicted the blunted response in the medialorbitofrontal cortex and ventral striatum, explicitly demonstrating themechanism underlying varenicline's property to reduce the effects ofsmoking cues on both the brain and craving.

"The results of our study reveal a distinctive new action that likelycontributes to its clinical efficacy," the authors conclude."Unsuccessful smoking cessation is more prevalent in individuals withpsychiatric illness, suggesting that they have greater difficultyquitting. Varenicline and other medications that can reduce bothwithdrawal and cue reactivity may be of special benefit to thesesubgroups who may also be more vulnerable to relapse in the presence ofsmoking cues."

Source: JAMA and Archives Journals