No abstract

Rationale Oral tobacco–derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST. Objectives To evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST). Methods We used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST. Results The mean nicotine Cmax for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine tmax was much longer for all NPs and OBMST (32.5–34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST. Conclusions Overall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products.

The purpose of this open‐label, randomized, controlled, in‐clinic, 5‐parallel‐group study was to assess biomarkers of exposure (BoE) to select harmful and potentially harmful constituents in adults who smoke (N = 144) switching to oral tobacco products (on!® mint nicotine pouches; test products) compared to continuing smoking cigarettes (CS) and completely quitting all tobacco products (NT). Changes in 20 BoE to select harmful and potentially harmful constituents, including 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL), were evaluated. Adult smokers smoked their usual brand of cigarettes for 2 days (baseline assessments) and then were randomly assigned to ad libitum use of 2, 4, or 8 mg test products, CS, or NT for 7 days. Analysis of covariance was used to assess the Day 7 BoE levels between each group using test products, CS, and NT. The creatinine‐adjusted total urinary NNAL and other 18 of 19 BoE levels (except nicotine equivalents [NEs]) were significantly lower (P < .05) on Day 7, among all test product groups compared to CS. Geometric least‐square means were reduced for all biomarkers of exposure, except NEs, in test product groups by approximately 42%–96% compared to the CS group, and reductions were comparable to the NT group. The geometric least‐square means for urinary NE between the test product and the CS groups, although not significantly different, the Day 7 mean change relative to the CS group were 49.9%, 65.8%, and 101% for the 2, 4, and 8 mg test product groups, respectively. The substantial reduction in harmful and potentially harmful constituent exposure suggests complete switching from cigarettes to test products may present a harm reduction opportunity for adults who smoke.