Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial

Introduction: The high morbidity and mortality caused by smoking highlights the importance of investigating new strategies for smoking cessation or reduction. Galantamine is an acetylcholinesterase inhibitor that increases the effect of acetylcholine (ACh). The nicotinic ACh receptor is activated via positive allosteric modulation (APL). Methods: We investigated whether galantamine reduces smoking by performing a 24-week randomized, placebo-controlled, multicentric clinical trial in recently detoxifled alcohol-dependent patients. We included all study subjects irrespective of an intention or motivation to abstain from nicotine. Specific treatment for cessation or reduction of smoking was not provided. Smoking behavior was assessed by means of patients' diaries. The nicotine metabolite cotinine was measured to verify the number of smoked cigarettes as documented in the patient's diary. Results: 114 randomized smokers received galantamine (n = 56) or placebo (n = 58) for 12 weeks. Follow-up examinations were terminated after an additional 12 weeks without treatment. Smoking behavior did not differ between both groups at baseline. After treatment, the intention-to-treat analysis revealed significant differences with a 20% lower cumulative number of smoked cigarettes and a 15% lower number of smoking days in the galantamine group compared to placebo. The average number of smoked cigarettes per smoking day as well as the cotinine values decreased about 10%. Cotinine values showed a positive correlation with the number of documented cigarettes, validating the patients' diaries. Conclusion: Our tentative data indicate that galantamine reduces smoking behavior even without any additional specific intervention. We suggest introducing the term "substitution therapy" into the treatment of smoking. This result could open up a new treatment approach for groups of patients which usually have a low motivation for change.