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Randomized Controlled Trial
. 2012 Nov 1;126(1-2):263-7.
doi: 10.1016/j.drugalcdep.2012.04.019. Epub 2012 May 15.

Cognitive effects of the acetylcholinesterase inhibitor, donepezil, in healthy, non-treatment seeking smokers: a pilot feasibility study

Rebecca L Ashare  1 , Riju Ray, Caryn Lerman, Andrew A Strasser
Affiliations
Randomized Controlled Trial

Cognitive effects of the acetylcholinesterase inhibitor, donepezil, in healthy, non-treatment seeking smokers: a pilot feasibility study

Rebecca L Ashare et al. Drug Alcohol Depend. .

Abstract

Background: There is a need to identify medications to aid in smoking cessation. Reducing withdrawal-related cognitive deficits represents a pharmacological target for new pharmacotherapies. Endogenous acetylcholine levels, which are modulated by acetylcholinesterase inhibitors (AChEIs), play an important role in smoking behavior and cognition. This pilot feasibility study tested whether an AChEI, donepezil, enhanced cognitive performance among healthy smokers.

Methods: Eighteen non-treatment seeking daily smokers (6 female) received either donepezil (5 mg q.d) or placebo (double-blind; 2:1 allocation ratio) for 4 weeks. Smoking rate, side effects, and neurocognitive measures of working memory (Letter-N-back) and sustained attention (Penn Continuous Performance Task) were assessed weekly.

Results: For the working memory task, there was a significant group×load×time interaction (p=0.03) indicating that the donepezil group demonstrated an increase in true positives from baseline to week 4 at the highest working memory load (3-back). The placebo group showed no change in accuracy. For the sustained attention task, there was a marginal effect in the same direction for discriminability, or d', p=0.08. There were no significant effects on reaction time during either task. There was also a reduction in cigarettes per day in the placebo group, but not the donepezil group.

Conclusions: AChEIs, such as donepezil, may have pro-cognitive effects among healthy smokers while they continue to smoke as usual. Given the association between cognitive deficits and relapse, AChEIs should be explored as potential therapeutics for smoking cessation.

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Conflict of interest statement

Conflict of Interest

Dr. Ray has also received grant funding for an independent study from Pfizer, which markets Aricept. Pfizer has no contributions towards funding, design, or analysis from this study. Dr. Ray is no longer at the University of Pennsylvania; he is now employed by GSK Biologicals. Dr. Lerman has served as a consultant to Pfizer on pharmacogenetic testing for smoking cessation treatment and has received research funding from and consulted for AstraZeneca, Targacept, Pfizer, and GlaxoSmithKline, for work unrelated to this manuscript. Dr. Lerman also reports receiving compensation for expert testimony. Dr. Strasser has previously received grant funding for an independent study from Pfizer through the GRAND programme.

Figures

Figure 1
Figure 1
Change in true positives from baseline to Week 4 during the Letter-N-Back task by group and N-back load level. For the donepezil group, the mean (SE) baseline values at each N-back were: 0-back, 14.6 (0.26); 1-back, 13.5 (0.53), 2-back 11.8 (0.82), and 3-back, 9.6 (0.83). For the placebo group, they were: 0-back, 14.9 (0.39); 1-back, 14.6 (0.77), 2-back 12.6 (1.2), and 3-back, 12.2 (1.2). The groups did not significantly differ at any load level at baseline, all ps>0.11. * group difference, p < 0.05
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