Effect of Galantamine on Short-term Abstinence

Galantamine, an FDA-approved treatment for Alzheimer's disease, is used to treat cognitive impairment by enhancing acetylcholine through inhibition of the enzyme, acetylcholinesterase. We propose randomized double-blind placebo-controlled study of short-term (23 days) treatment with galantamine. Eighty chronic smokers will complete a validated procedure for screening new medications. An equal number of subjects will be assigned to one of two groups: galantamine-ER or placebo. Participants in both groups will take one capsule each day and follow the same procedures. This is not a cross-over trial. For participants in the galantamine group, following an initial 1-week drug run-up phase (8mg daily of galantamine-ER), the medication dose will be increased to 16mg daily of galantamine-ER for the remainder of the study (up to Day 23). On Day 15, smokers will begin a mandatory 24-hour abstinence period, which will be followed by a programmed smoking lapse on Day 16. Smokers will then be instructed to abstain for the following 7 days (observed abstinence). Following completion of the study, participants will be offered standard smoking cessation treatment. On Days 0 (Baseline), 14, and 16, subjects will perform the following computer tasks: a working memory task (Visual/Spatial N-Back), sustained attention tasks (Penn Continuous Performance Task \[PCPT-nl\] and XO Reaction Time Task), a recall memory task (Word Recognition), an interference control task (Stroop test), and a response inhibition task (Stop Signal Task). The primary outcome is to identify changes in behavioral performance and subjective symptoms following two weeks treatment of galantamine and after 24 hours of abstinence, compared to baseline. This study will provide information about the role of the cholinergic system during brief abstinence and whether enhancing acetylcholine reduces abstinence-induced cognitive symptoms that promote smoking relapse. Information obtained in this study may further establish cognitive performance measures as endophenotypes for nicotine dependence.