New types of modern oral tobacco products (MOTP), including tobacco-free nicotine lozenges, pouches, and gum, are available to adult tobacco consumers and are increasingly being used in the US. There is a regulatory and public health interest in understanding the abuse liability (AL) of these new products compared to other marketed tobacco and nicotine-containing products, but the empirical evidence is limited. We conducted two clinical studies to test the AL of 1) hard and soft forms of nicotine lozenges and 2) portioned oral nicotine pouches in two nicotine levels. These studies were conducted over 6 days in confinement with subjects using one of five test products in daily test sessions including: mint-flavored variants of nicotine lozenges (one nicotine level); mint-flavored variants of a nicotine pouch (two nicotine levels); and high- and low-AL comparators (combustible cigarette [CC] and oral nicotine replacement therapy [NRT]). Following FDA recommendations for AL assessment of pharmaceuticals, subjects used multiple products simultaneously for one or two test sessions to achieve nicotine levels above what is available in commercially available products. Subjective measures and nicotine pharmacokinetic (PK) characteristics before, during, and after product use were assessed over several hours.

The PK parameters for the commercially-available MOTP were more similar to NRT than CC. Increasing nicotine uptake by simultaneous use of multiple products negatively affected subjective measures such as product liking and positive effects and increased the incidence of adverse events. Collectively, these data suggest lower AL for MOTP as compared to CC and similar or lower AL as compared to commercially available oral NRTs.