Nicotine addiction continues to be the main cause of preventable death in developed countries, with an estimated 435,000 premature deaths in the U.S. alone. Despite the availability of effective pharmacotherapies, 70 to 90% of smokers resume smoking within a year of treatment. Accordingly, the development of novel and effective nicotine dependence pharmacotherapies continues to be an important goal. In an effort to identify novel therapies for nicotine addiction, we recently conducted a pilot study using galantamine (GAL) as a treatment for smokers. GAL enhances cholinergic transmission by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine. Acetylcholine is the endogenous neurotransmitter for the nicotinic and muscarinic type cholinergic receptors. GAL also directly potentiates the activation of nicotinic acetylcholine receptors. In our study, a 4-da GAL treatment (8 mg/day) attenuated some of the subjective effects from intravenous (IV) nicotine when compared with placebo. Furthermore, GAL reduced the craving for cigarettes and improved performance on a Go No-Go task. These findings, together with other preclinical and clinical studies, support the potential efficacy of GAL as a treatment for nicotine addiction. To extend our preliminary findings, we propose a double-blind, placebo-controlled, between-subjects study that will randomize 72 smokers to receive GAL (8 mg/day, 16 mg/day), or a placebo treatment for a total of 7 weeks. Following 2 weeks of dose titration, smokers will complete a laboratory session that measures smoking behavior. In the subsequent 4-week treatment phase, smokers will continue their assigned medication and will attempt to quit smoking. During this phase, measures of smoking behavior (self-report and cotinine), withdrawal severity, and cognitive performance will be obtained. To our knowledge, this is the first study examining the therapeutic potential and the mechanism of action of GAL for the treatment of tobacco dependence.

Public Health Relevance

Tobacco addiction is the most important preventable cause of death in the U.S., however, the majority of smokers do not benefit from the currently available pharmacotherapies. This proposal will examine the safety and efficacy of GAL as a treatment for nicotine addiction. The results of this study may lead to development of a novel treatment for smoking cessation.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Walton, Kevin
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Yale University
Schools of Medicine
New Haven
United States
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DeVito, Elise E; Carroll, Kathleen M; Sofuoglu, Mehmet (2016) Toward Refinement of Our Understanding of the Fundamental Nature of Addiction. Biol Psychiatry 80:172-3