This clinical trial evaluates the effect of nicotine on eye movements and related behaviors in people who use electronic (e)-cigarettes. Nicotine is an addictive, poisonous chemical found in tobacco. It can also be made in the laboratory. When it enters the body, nicotine causes an increased heart rate and the use of oxygen by the heart and a sense of well-being and relaxation. E-cigarettes are the most commonly used tobacco products in young adults in the United States. E-cigarettes deliver nicotine rapidly and the potential for addiction (abuse liability) is comparable to combustible cigarettes. The Food and Drug Administration uses a combination of testing including self-reported scales, withdrawal assessments and behavioral tasks to evaluate the abuse liability of a nicotine product. Research has shown that nicotine alters movement of the eye (oculomotor) and the amount of nicotine in the blood impacts the extent of oculomotor function impairment. Despite this evidence linking nicotine to oculomotor changes, it has not been studied as a reliable marker for abuse in e-cigarette users. Studying eye movements can provide information about how the brain responds to nicotine and may help researchers develop better, more objective ways to measure how addictive nicotine products in e-cigarette users.

PRIMARY OBJECTIVE:

I. To determine the between-session reliability of oculomotor biomarkers during standardized nicotine administration in daily e-cigarette users.

SECONDARY OBJECTIVES:

I. To evaluate the association between oculomotor (OM) responses to nicotine and behavioral economic indices of reinforcing value.

II. To assess the relationship between oculomotor changes and nicotine withdrawal relief.

OUTLINE:

Participants abstain from nicotine for at least 12 hours and caffeine products for at least 2 hours, as well as obtain sleep for at least 5-6 hours before each study visit. Participants self-administer 5% nicotine non-mint menthol pods via an e-cigarette device using a guided standardized puffing routine over 5 minutes on visit one. At least 48 hours later, participants complete the same 5-minute guided puffing routine as in visit one and then use an e-cigarette as they normally would over 30 minutes at visit two. Participants also complete eye movement testing and undergo blood sample collection during each visit.

Inclusion Criteria:

• Age 21-50 years
• Daily use of nicotine-containing electronic cigarettes for ≥ 6 months
• Ability to abstain from nicotine for at least 12 hours prior to study visits
• Fluent in English
• Willingness to complete two in-person laboratory visits and all study procedures
• Ability to provide informed consent

Exclusion Criteria:

• Use of combustible cigarettes or other tobacco/nicotine products on more than 5 of the past 30 days
• Current enrollment in a nicotine cessation program or intent to quit in the next 30 days
• Neurological conditions affecting eye movements (seizure disorder, movement disorders, head injury with loss of consciousness)
• Normal or corrected-to-normal vision required; significant uncorrected visual impairment or ocular conditions affecting eye tracking
• Cardiovascular conditions for which nicotine use is contraindicated, substance use disorder (other than nicotine), or current nicotine cessation treatment
• Pregnancy or breastfeeding
• Current medications affecting pupil size or eye movements (anticholinergics, stimulants, antipsychotics)
• Any condition that, in the investigator's judgment, would interfere with safe participation
• Age younger than 21 years or older than 50 years