Semaglutide-Induced Reduction in Nicotine Craving and Use: A Case-Based Insight

Abstract

Tobacco use remains a leading cause of preventable morbidity and mortality worldwide, with smoking cessation efforts often hindered by high relapse rates. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for the treatment of type 2 diabetes and obesity, have recently garnered attention for their potential modulatory effects on reward pathways implicated in substance use disorders. This case report describes a 29-year-old male patient with obesity who experienced a significant reduction in nicotine dependence following the initiation of once-weekly semaglutide for weight management. Within two months, the patient’s Fagerström Test for Nicotine Dependence score decreased from moderate to minimal dependence, accompanied by aversive reactions to the taste and smell of cigarettes, as well as a reduction in alcohol consumption. Preclinical studies have demonstrated that GLP-1 receptors are expressed in critical neuroanatomical regions such as the ventral tegmental area and nucleus accumbens, where their activation modulates dopaminergic signaling involved in nicotine reinforcement and relapse. Emerging clinical data support these findings, suggesting that GLP-1RAs may reduce cravings and alleviate psychiatric comorbidities that contribute to relapse in substance use disorders. Moreover, semaglutide’s anorexigenic properties may help counteract post-cessation weight gain—a known barrier to sustained abstinence. Although spontaneous remission cannot be entirely ruled out, the temporal relationship and absence of confounding factors in this case point to a pharmacological effect of semaglutide on nicotine use behavior. Challenges to broader clinical implementation include high cost, limited accessibility and the absence of formal treatment guidelines. This report underscores the need for further rigorous research, including randomized controlled trials, to clarify the therapeutic potential of GLP-1RAs in nicotine use disorder, particularly among patients with comorbid metabolic conditions.