The Effect of Flavor and Nicotine Strength on the Abuse Liability and Appeal of Oral Nicotine Products

E-cigarettes (ECs) have been the predominant flavored non-combustible tobacco product used by young adults since 2014, and are disproportionately used by sexual/gender minorities (SGM). However, patterns are likely to change due to: 1) increasing regulatory restrictions on non-tobacco flavored ECs, and 2) the emergence new nonmedicinal oral nicotine products (ONPs; e.g., pouches and gums) with enhanced palatability (e.g., improved flavoring). Preliminary data shows that many young adult e-cigarette users with no intention to quit vaping perceive ONPs as secondary means of nicotine consumption when vaping is prohibited.

Because EC+ONP dual use could exacerbate nicotine dependence by increasing daily nicotine intake, it is important to identify drivers of ONP appeal and abuse liability in young adult EC users to inform regulations that prevent adverse dual use in young people. Nicotine concentration and flavors are two putative drivers of ONP appeal and abuse liability, given that ONPs deliver substantial buccal nicotine absorption and, like ECs, their flavors elicit pleasant sensory effects. Certain ONP flavors may offset nicotine's oral irritating effects via anesthetizing cooling effects (mint flavored ONPs with menthol), allowing tolerability of higher doses of nicotine.

ONP type may also be important to ONP appeal. Initial evidence (primarily product interest survey data) suggests young adult EC users and adolescents may have higher affinity for nicotine gum than pouches, and interest in using ONPs was greater within certain vulnerable populations, especially SGMs. The investigators will determine the appeal and abuse (including dual use) liability of gum and pouch ONPs as a function of flavor (mint vs fruit) and nicotine concentration (gum 2mg vs. 6mg; pouch 2mg vs. 6mg) among young adult exclusive EC users (N = 320; ages 21 - 25). Data will be collected via virtual study sessions in which participants residences become 'remote laboratories' (allowing nationwide quota sampling). Following an orientation, participants will be randomized to one of two ONP types (gum or pouch) and nicotine concentrations (low vs. high), resulting in four study groups. The randomized nicotine-ONP combination will then be tested in: (i) a single-visit appeal/sensory attribute testing involving controlled self-administration of mint and fruit flavored ONPs; and (ii) two abuse liability evaluations (one for fruit one for mint) each involving a single-visit controlled ONP self-administration session and 1-week post-visit naturalistic use of the respective ONP.

Overview of Project The investigators will utilize an experimental design to determine the acute appeal and abuse liability of gum and pouch ONPs among young adult current EC users. Data will be collected via three online sessions with participants from across the US in which their own residences become a 'remote lab.' Following an orientation session, participants will be randomized to one of four groups varied by product type (a gum or pouch) and nicotine concentration (low [2mg] or high [6mg]) and receive that type and nicotine level throughout the entire protocol.

• Experimental Session 1 (Sensory Appeal session): Collect ratings appeal and sensory attributes directly after self-administering 2 fruit (e.g., citrus, pomegranate) and 2 mint (e.g., spearmint, wintergreen) flavored variants of their ONP type/nicotine condition in a single visit. Order of the 4 flavors will be in one of 24 possible sequences randomly assigned for each participant. The highest rated fruit variant and highest rated mint variant will be selected for the subsequent two sessions.
• Experimental Sessions 2 & 3 (Abuse Liability sessions): Involve 30-min self-administration of one ONP (fruit ONP in one session, mint ONP in another session; order counterbalanced) in separate sessions after 18-hours of abstinence. Dependent variables will include withdrawal/urge suppression, subjective effects, and behavioral economic indicators of reward value. In addition, for the 7 days after each abuse liability session visit participants will report on naturalistic use of the same product (a free provision of 30 pieces of each product that was administered in the previous Abuse Liability session will be provided to participants to use ad lib).