Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial

Introduction:
This article reports the results of a randomized crossover study evaluating the role of nicotine stereoisomer on nicotine pouch abuse liability. The study compares systemic nicotine exposure and product appeal of oral nicotine pouches (ONPs) containing more than 99% S-nicotine versus racemic nicotine. The key points and main message of this study are summarized below.

Key Points:

* The study enrolled 18 adult smokers who used wintergreen-flavored, 3 mg nicotine ONPs during three visits, following at least 12 hours nicotine abstinence.
* The first ONP contained more than 99% S-nicotine, and the other two ONPs contained racemic nicotine.
* Plasma nicotine assessments and measures of withdrawal relief occurred at multiple time points, and product appeal was assessed following ONP use.
* Using the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90 minutes and greater maximum plasma nicotine concentration compared to the ONPs with racemic nicotine.
* Product liking and withdrawal relief were similar across ONPs, although participants reported more "bad effects" when using the ONP with more than 99% S-nicotine.

Main Message:
The findings suggest that ONPs with more than 99% S-nicotine might be better substitutes for cigarettes than racemic nicotine ONPs. However, additional research is needed to inform comprehensive product regulations to support public health, including the roles of flavorings, total nicotine concentration, and freebase nicotine in the abuse liability of oral nicotine pouches.

Brittney Keller-Hamilton, Hayley Curran, Mahmood Alalwan, Alice Hinton, Marielle C Brinkman, Ahmad El-Hellani, Theodore L Wagener, Kirsten Chrzan, Leanne Atkinson, Sriya Suraapaneni, Darren Mays, Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial, Nicotine & Tobacco Research, Volume 27, Issue 4, April 2025, Pages 658–665, https://doi.org/10.1093/ntr/ntae079