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Drug Alcohol Depend. 2013 Jun 1;130(1-3):135-41. doi: 10.1016/j.drugalcdep.2012.10.021. Epub 2012 Nov 30.

Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers.

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Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States.



The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome.


This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design.


Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-min intervals. At 4-h post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil.


At 4-h post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results.


Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.

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