Research on tobacco product standards to limit the abuse liability of electronic nicotine delivery systems has primarily focused on nicotine concentration and flavor profiles. Other liquid characteristics, such as protonated nicotine ratio and sweet enhancer additives, are less understood but may serve as regulatory targets. This clinical laboratory study examined the effects of electronic nicotine delivery system protonated nicotine ratio and the presence of a sweet enhancer on nicotine delivery, use behavior, and subjective effects. Thirteen participants completed four sessions that varied by protonated ratio (0:100 vs. 40:60 freebase to protonated nicotine) and sweet enhancer content (unsweetened vs. sweetened with ethyl maltol). Each session included a 10-puff directed use period and a 30-min ad libitum use period, followed by an own brand challenge. Measures included heart rate, subjective effects, plasma nicotine concentration, and liquid consumption. Results revealed that protonated ratio significantly influenced nicotine delivery, use behavior, and subjective effects. The 0:100 conditions produced greater nicotine boost, longer puff duration, and larger puff volume compared to the 40:60 conditions. Sweet enhancer did not impact nicotine delivery but boosted flavor perception and appeal when combined with the 0:100 ratio. Unsweetened liquids were associated with greater nausea, while 40:60 conditions were perceived as harsher and more irritating. The 0:100 liquids increased concentration ratings, whereas 40:60 liquids elicited greater immediate desire to use again. These findings underscore the need for electronic nicotine delivery system product standards to consider not only nicotine concentration but also nicotine form and sweet enhancers to effectively reduce abuse liability. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Carrico et al. (Thu,) studied this question.