Nicotine pharmacokinetics and abuse liability of commercially available tobacco products: an open-label, randomized, controlled study

This clinical study evaluated the abuse liability and nicotine pharmacokinetics of five tobacco products: conventional cigarettes, heated tobacco products (HTPs), e-cigarettes, snus, and tobacco-free nicotine pouches (NPs). In a controlled, randomized trial with adult smokers, we assessed serum nicotine concentrations and subjective effects following product use. Inhaled products (cigarettes, HTPs, e-cigarettes) showed rapid nicotine absorption, peaking within 5–6 min, while oral tobacco products exhibited delayed absorption (T max 36–39 min) with lower peak concentrations. Although total nicotine exposure was similar for cigarettes and tobacco-derived pouches, cigarettes delivered a significantly higher early nicotine boost. Subjective effects correlated with pharmacokinetic data, revealing higher liking and craving scores for inhaled products. The findings demonstrate that abuse liability is directly linked to nicotine delivery speed and intensity, with oral tobacco products presenting a lower-risk profile. This supports the role of low-abuse-liability products in tobacco harm reduction strategies. Registration number: ChiCTR2500104299 (June 13, 2025).