Kanobe Milly N, Powell Christie Y, Patrudu Makena, Baxter Sarah A, Tapia Melissa A, Darnell John, Prevette Kristen, Gibson Alison G, Ayoku Sarah A, Campbell Leanne, Coffield Jeffrey W, Keyser Brian M, Ganesh Bhagya Sukka, Gale Nathan, Jordan Kristen G
RAI Services Company, Winston-Salem, NC, United States.
BAT (Investments) Limited, Research and Development, Southampton, United Kingdom.
Front Pharmacol. 2025 Mar 13;16:1547073. doi: 10.3389/fphar.2025.1547073. eCollection 2025.
Oral nicotine pouches (ONPs) are a newer category of smokeless tobacco products containing pharmaceutical-grade nicotine but no tobacco leaf. These products have the potential to help smokers transition away from cigarettes. To assess their potential role as alternatives to cigarettes, we evaluated the abuse liability (AL) of Velo ONPs with varying nicotine content (4-12 mg per pouch), pouch size (600 mg or 400 mg) and flavor (six varieties) in comparison to high (cigarettes) and low (nicotine replacement therapy [NRT] gum) AL comparators.
Independent randomized crossover clinical studies were conducted to assess AL, including subjective effects (product liking [PL], urge to smoke, product effects, overall PL, and overall intent to use again) and nicotine pharmacokinetic (PK) parameters of Velo ONPs. Participants used test products under controlled conditions, and subjective effect measures were collected using validated questionnaires. Nicotine PK parameters, including peak nicotine concentration (C), time to maximum concentration (T), were assessed.
Mean PL scores for all Velo ONPs (p < 0.0042) and Velo Mini Pouches (p < 0.0031) were significantly lower than cigarettes, regardless of nicotine level, pouch size, or flavor, but similar to NRT gum. Other subjective measures for Velo ONPs were less favorable than cigarettes and comparable to or lower than NRT gum. Nicotine uptake with Velo ONPs was slower (reflected by a longer T) and had lower C than cigarettes but was comparable or slightly lower than NRT gum. Overall nicotine uptake increased with increasing nicotine content and was comparable to that of cigarettes for Velo ONPs with higher nicotine levels. Flavor had no effect on nicotine uptake of Velo ONPs.
Velo ONPs demonstrated an AL profile lower than cigarettes and similar to NRT gum, suggesting a reduced potential for abuse compared to cigarettes. The slower nicotine uptake and lower peak nicotine levels further support their potential as a lower-risk alternative. These findings highlight the potential role of ONPs in tobacco harm reduction strategies by providing an alternative nicotine source with a lower AL than combustible cigarettes.
The clinical studies were registered at ClinicalTrials.gov; NCT05129657, NCT05294497, and NCT05081154.
口服尼古丁袋（ONP）是一类较新的无烟烟草产品，含有药用级尼古丁但不含烟叶。这些产品有可能帮助吸烟者从香烟转向其他产品。为了评估它们作为香烟替代品的潜在作用，我们评估了不同尼古丁含量（每袋4 - 12毫克）、袋大小（600毫克或400毫克）和口味（六种）的Velo ONP与高滥用可能性（香烟）和低滥用可能性（尼古丁替代疗法[NRT]口香糖）对照物相比的滥用可能性（AL）。
进行了独立随机交叉临床研究以评估AL，包括主观效应（产品喜好[PL]、吸烟冲动、产品效果、总体PL和再次使用的总体意愿）以及Velo ONP的尼古丁药代动力学（PK）参数。参与者在受控条件下使用测试产品，并使用经过验证的问卷收集主观效应测量值。评估了尼古丁PK参数，包括尼古丁峰值浓度（C）、达到最大浓度的时间（T）。
无论尼古丁水平、袋大小或口味如何，所有Velo ONP（p < 0.0042）和Velo迷你袋（p < 0.0031）的平均PL得分均显著低于香烟，但与NRT口香糖相似。Velo ONP的其他主观测量结果不如香烟，与NRT口香糖相当或更低。Velo ONP的尼古丁吸收较慢（以较长的T反映）且C低于香烟，但与NRT口香糖相当或略低。总体尼古丁吸收随着尼古丁含量的增加而增加，对于尼古丁水平较高的Velo ONP，其总体尼古丁吸收与香烟相当。口味对Velo ONP的尼古丁吸收没有影响。
Velo ONP的AL特征低于香烟且与NRT口香糖相似，表明与香烟相比滥用可能性降低。较慢的尼古丁吸收和较低的尼古丁峰值水平进一步支持了它们作为低风险替代品的潜力。这些发现突出了ONP在烟草危害减少策略中的潜在作用，即提供一种AL低于可燃香烟的替代尼古丁来源。
临床研究已在ClinicalTrials.gov注册；NCT05129657、NCT05294497和NCT05081154。
