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Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

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Abstract

Rationale

The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas.

Objectives

This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals.

Methods

Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC).

Results

Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas.

Conclusions

These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.

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Acknowledgements

Portions of this work were presented at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta) and the 52nd Annual Meeting of the American College on Neuropsychopharmacology (December 2013, Hollywood, FL). This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), including the Charleston Alcohol Research Center (P50 AA010761). NIAAA had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by K99 AA021419 and K05 AA017435, respectively.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Joseph P. Schacht, Raymond F. Anton, Patrick K. Randall, Xingbao Li, Scott Henderson & Hugh Myrick

  2. Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA

    Hugh Myrick

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  1. Joseph P. Schacht
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  2. Raymond F. Anton
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  3. Patrick K. Randall
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  4. Xingbao Li
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  5. Scott Henderson
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  6. Hugh Myrick
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Correspondence to Joseph P. Schacht.

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Schacht, J.P., Anton, R.F., Randall, P.K. et al. Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals. Psychopharmacology 231, 3799–3807 (2014). https://doi.org/10.1007/s00213-014-3518-1

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  • DOI: https://doi.org/10.1007/s00213-014-3518-1

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