The goal of this application is to test whether menthol and fruit flavors impact e-cigarette use through dissociable mechanisms and exert their effects differentially across nicotine doses.

This study examines the impact of menthol and fruit flavors on self-administration of e-cigarette solutions containing varying amounts of nicotine. This is a randomized, double-blind study with a within-subject cross-over design, using e-liquids with 5 different flavors and 4 different levels of nicotine for a total of 20 different e-liquid formulations. Each subject will participate in 4 test sessions. The order of flavor and nicotine delivery will be randomized. At each test session, they will undergo directed self-administration, in a randomized order, then an ad libitum self-administration session where they can choose among all of the e-cigarettes used during the directed session. The primary aims assess the impacts of nicotine and flavor (and their interactions) on participants' subjective ratings of the e-liquids during the 'directed' self-administration component, and self-administered puffs during the ad libitum self-administration component. In addition, the study will explore the impact of sex/gender and sensitivity to nicotine aversiveness or bitterness (as operationalized by genetic variations in the alpha-5 subunit of nicotinic acetylcholine receptor that influences the aversive effects of nicotine, or a taste receptor number 38 ( TAS2R38) important for bitterness perception) on study outcomes.

INCLUSION CRITERIA

• Aged 18 to 30;
• Past month daily nicotine-containing e-cigarette, cigarette, and/or cigar/little cigar/cigarillo use;
• Urine cotinine levels consistent with regular nicotine use (e.g., NicAlert urine cotinine dipstick ≥3 or Accutest Positive for Cotinine);
• For females, using acceptable birth control methods;
• Able to provide written informed consent;
• Able to read and write in English;
• Stated willingness to comply with all study procedures (including self-administration of all e-liquid conditions; attend in-person sessions; comply with COVID guidelines of the research facilities) and lifestyle considerations (including overnight nicotine abstinence) and availability for the duration of the study;
• Cardiovascular measures in normal/ non-hypertensive range for adults, including resting heart rate (HR) of 60-100 bpm; blood pressure (BP) of equal to or less than 129 mmHg (systolic)/80 mmHg (diastolic)); and oximeter (i.e., blood oxygenation) readings of 95-100 SpO2;
• Resident of the State of Connecticut.

Exclusion Criteria:

• Any allergy or known hypersensitivity to propylene glycol, vegetable glycerin, menthol, mint, green apple or watermelon flavorants or history of allergic or hypersensitive reaction to use of an e-cigarette/vaping device;
• Has not used e-cigarettes at least 10 times in the last 6 months;
• For females, pregnant (as determined by pregnancy screening) or breast feeding;
• Seeking (or undergoing) treatment for nicotine dependence or tobacco product use (smoking or vaping) or has current plans to quit tobacco product use;
• Meet current criteria for psychiatric disorder (according to the MINI);
• Current or history of respiratory illnesses including pneumonia with COVID-19 , other medical illness, and/or psychotropic medication use that a clinician investigator deems a contraindication for study participation.
• History of environmental - bronchospastic allergies, multiple chemical sensitivities, or other airway sensitivities that require the use of an epi pen or that in the investigators view would make it risky for participation;
• Not fully vaccinated for COVID-19

This is a double-blind study. Although participants will receive all conditions in this within-subject cross-over study, the participant and researcher will be blinded to the order of e-liquid conditions (nicotine level, flavor) across and within test sessions.