Pathology of oral nicotine pouches and their addiction mechanisms.
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INTRODUCTION/OBJECTIVES: Oral nicotine pouches (ONPs) represent a recent and rapidly growing category of tobacco-free nicotine delivery systems. Their discreet, spit-free nature and wide array of sweet, fruit-flavored options have driven significant popularity, particularly among youth and young adults. This surge in use, often as a first nicotine product, demands a critical examination of their potential pathological effects on oral and systemic health. Furthermore, the efficient delivery of nicotine salt from these products necessitates a thorough investigation into their addictive properties and potential to create a new generation of nicotine-dependent individuals. DATA SOURCES: A thorough literature search was conducted with PubMed and Google Scholar. STUDY SELECTION: Relevant clinical, epidemiological, and mechanistic studies on ONPs and their health effects were included in this review. CONCLUSIONS: ONPs eliminate combustion and tobacco leaf, reducing exposure to many carcinogens compared with cigarettes or snus. However, nicotine and flavor additives induce localized mucosal pathology, commonly presenting as white hyperkeratotic lesions with histological features of hyperkeratosis, edema, and inflammation, mediated by oxidative stress and NF-κB/NLRP3 signaling. Systemically, nicotine absorption via the oral mucosa provokes sympathetic activation, acutely elevating blood pressure and heart rate. ONPs deliver substantial nicotine doses that support sustained use and neuroadaptations in nicotinic acetylcholine receptors and reward pathways, reinforcing dependence. Adolescents and nicotine-naïve individuals are particularly vulnerable due to the products' discreet profile and appealing flavors. While ONPs may lower cancer risk compared with combustible tobacco, their long-term oral health consequences and potential to perpetuate nicotine dependence remain uncertain, requiring further study and regulatory oversight. CLINICAL SIGNIFICANCE: The rise of ONPs presents a dual challenge for public health. Clinically, practitioners are urged to screen for oral mucosal lesions associated with ONP use and counsel patients on their addictive potential. On a regulatory level, policymakers must navigate a delicate balance between facilitating harm reduction for established adult smokers and implementing measures to prevent the initiation of use in younger populations.