Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal.
BACKGROUND
Current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, there is a clear need to develop novel antismoking medications. Nicotine withdrawal is associated with cognitive impairments that predict smoking relapse. It has been proposed that these cognitive deficits are a hallmark of nicotine withdrawal that could be targeted in order to prevent smoking relapse. Thus, pharmacotherapies that increase cognitive performance during nicotine withdrawal may represent potential smoking cessation agents.


METHODS
The authors review the clinical literature demonstrating that nicotine withdrawal is associated with deficits in working memory, attention and response inhibition. They then briefly summarize different classes of compounds and strategies to increase cognitive performance during nicotine withdrawal. Particular emphasis has been placed on translational research in order to highlight areas for which there is strong rationale for pilot clinical trials of potential smoking cessation medications.


CONCLUSIONS
There is emerging evidence that supports deficits in cognitive function as a plausible nicotine withdrawal phenotype. The authors furthermore believe that the translational paradigms presented here may represent efficient and valid means for the evaluation of cognitive-enhancing medications as possible treatments for nicotine dependence.
University of Pennsylvania, Perelman School of Medicine, Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry , 3535 Market St, Suite 4100, Philadelphia, PA 19104 , USA +1 215 746 5789 ; rlashare@mail.med.upenn.edu.
Rebecca L
RL
Ashare
Heath D
HD
Schmidt
D003071:Cognition / Q000187:drug effects*; D006801:Humans; D009538:Nicotine / Q000009:adverse effects; D012008:Recurrence; D012907:Smoking / Q000523:psychology; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000523:psychology; D014029:Tobacco Use Disorder / Q000534:rehabilitation*; D057170:Translational Research, Biomedical
D009538:Nicotine
cognition; nicotine; reinstatement; relapse; self-administration; smoking; tobacco; withdrawal