Study: fMRI visualizes allaying of cravings by anti-smoking meds

Treatment with the anti-smoking medications bupropion and varenicline was associated with diminished cravings, weakened withdrawal symptoms and reduced activation in regions of the brain associated with cravings and withdrawals from smoking, according to a pair of studies published online Jan. 3 in the Archives of General Psychiatry.

Functional MRI (fMRI) has demonstrated increased activity among nicotine-dependent individuals in several regions of the brain, including the prefrontal cortex, amygdala, ventral tegmental area, (ventral) striatum and the medial orbitofrontal cortex. This heightened activation has been associated with nicotine-dependent persons' responses to smoking cues, which researchers believe indicates that cues induce symptoms of withdrawal and/or cravings. The researchers in these studies investigated variations in brain activity, according to fMRI, among patients who were taking the smoking cessation medications bupropion or varenicline.

In the first study, 30 patients were randomly assigned to take either bupropion or a placebo for eight weeks.Before and after watching videos of smoking cues or neutral footage, particpants reported their subjective cravings and underwent fMRI scans.

The researchers found that patients treated with bupropion reported significantly lower craving levels than patients taking the placebo, while also experiencing significantly larger reductions in cravings over the course of the treatment. In addition, patients taking bupropion demonstrated reduced limbic and prefrontal activation, which are associated with cravings to smoke. Finally, all participants' subjective cravings aligned with their fMRI results—less activation correlated with reduced 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," concluded Christopher S. Culbertson, PhD, of the department of psychiatry at the University of California Los Angeles, and colleagues.

In the second study, 22 smokers were randomly selected to receive either placebo or varenicline, a smoking cessation medication aimed at reducing withdrawal symptoms and partially blocking the positive reinforcement garnered from smoking. As in the bupropion study, participants underwent fMRI at the outset and upon completion of the three-week treatment, with images taken to gauge subjects' responses to video smoking cues.

The authors found that smoking cues elicited significantly greater activation of the ventral striatum and medial orbitofrontal cortex and induced more subjective cravings than non-cue videos. After treatment, though, "[a]dministration of varenicline diminished smoking cue-elicited ventral striatum and medial orbitofrontal cortex responses (t values from -3.75 to -5.63) and reduced self-reported smoking cue-elicited craving, whereas placebo treated subjects exhibited responses similar to those observed prior to randomization," explained Teresa Franklin, PhD, of the department of psychiatry at the University of Pennsylvania in Philadelphia, and co-authors.

In addition to concluding that both bupropion and varenicline reduce cravings or withdrawals as well as smoking cue-induced brain activation, Culbertson and colleagues wrote that "[t]reatment with bupropion is associated with improved ability to resist cue-induced craving." Moreover, Franklin and colleagues concluded that the "results of our study reveal a distinctive new action of varenicline that may contribute to its clinical efficacy...Unsuccessful smoking cessation is more prevalent in individuals with psychiatric illness, suggesting that they have greater difficulty quitting. Varenicline and other medications that can reduce both withdrawal and cue reactivity may be of special benefit to these subgroups."

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