Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study

Abstract

Background and aims: Oral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes.

Design: This was a single-blind, three-visit (≥ 48-hour washout), randomized-cross-over study. Participants were encouraged to complete all study visits in less than 1 month.

Setting: The study took place in Rural/Appalachian Ohio.

Participants: Participants comprised 30 adults who smoke cigarettes. Participants (mean_age = 34.5) were 60% men and 90% White.

Intervention: Participants who were ≥ 12-hour tobacco-abstinent used: (1) a 3-mg nicotine concentration ONP, (2) a 6-mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes.

Measurements: Plasma nicotine and self-reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes.

Findings: At t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3- and 6-mg nicotine ONPs (P = 0.001) and between the 6-mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP.

Conclusions: Among adult smokers, using 6-mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3-mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

Trial registration: ClinicalTrials.gov NCT05236894.

Keywords: Cigarettes; health disparities; misuse liability; nicotine; oral nicotine pouches; rural.

FIGURE 1

Randomized cross-over study flow chart, Ohio, 2022. ^aIV line could not be placed. ^bParticipants who were lost to follow-up but had complete data for the visits they completed were included in analyses. ^cThree participants were excluded due to inconsistent reporting on use of other tobacco products between the screener and clinic visit survey. Two participants (both completed visit 1 only) were excluded due to missing data in measures used for analysis. ONP = oral nicotine pouch.

FIGURE 2

Plasma nicotine delivery associated with using 3 mg nicotine concentration oral nicotine pouches (ONPs), 6 mg nicotine concentration ONPs and usual brand cigarettes among adults who smoke cigarettes, Ohio, 2022. ^aFor ONP use sessions, participants used one ONP (Zyn brand) for 30 minutes while holding it in the same location between their upper lip and gum. For cigarette smoking sessions, participants took one puff from their usual brand cigarette every 30 s for 5 minutes. Error bars represent 95% confidence intervals. ^bStatistically significant difference between usual brand cigarette and 3 mg nicotine concentration ONP (P < 0.01). ^cStatistically significant difference between usual brand cigarette and 6 mg nicotine concentration ONP (P < 0.01). ^dStatistically significant difference between 3 mg nicotine concentration ONP and 6 mg nicotine concentration ONP (P < 0.01).

FIGURE 3

Withdrawal relief associated with using usual brand cigarettes, oral nicotine pouches (ONPs) with 3 mg nicotine concentration and ONPs with 6 mg nicotine concentration among adults who smoke cigarettes, Ohio, 2022. ^aWithdrawal measures were assessed immediately before ONP use or smoking (t = 0 minutes) and at t = 5, 15, 30, 60 and 90 minutes. Total Minnesota Withdrawal Scale (MNWS) scores were log-transformed for analysis. Error bars represent 95% confidence intervals. ^bStatistically significant difference between usual brand cigarette and 3 mg nicotine concentration ONP (P < 0.0001). ^cStatistically significant difference between usual brand cigarette and 6 mg nicotine concentration ONP (P < 0.0001).