Impact of Sweeteners on the Addictive Threshold of Nicotine

Participants will complete an Adaptation Session followed by four Test Days. The Adaptation Session will familiarize participants with all study procedures. On each Test Day, a specific intravenous nicotine dose (0.05 or 0.1 mg/pulse) is paired with either a sucralose or control flavor administered by an electronic cigarette. The experimental procedure begins with a sampling phase comparing the assigned nicotine dose against saline, each paired with the assigned flavor, followed by four trials to assess the participant's ability to discriminate between the two conditions. Subsequently, participants complete four Choice trials, where they will choose between receiving the assigned nicotine dose and saline. Reinforcement will be measured by the percentage of nicotine choices, while discrimination will be measured by the percentage of correctly identified infusions. Subjective rewarding effects will be assessed using the "Pleasurable Effects" composite score of the Drug Effects Questionnaire (DEQ).

Inclusion criteria

• Smoking at least for one year and more frequently than once a week, smoking status confirmed with a semi-quantitative urine nicotine test. Smokers will be stratified by level of dependence, assessed with the FTND 29 low or no dependence ≤3 and moderate or high dependence ≥ 4.
• In good health as verified by medical history, screening examination, and screening laboratory tests.
• For women, report using acceptable birth control methods.

Exclusion criteria

• History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study;
• regular current use of certain psychotropic medications (such as mood stabilizers, antipsychotics, or anxiolytics being prescribed to treat bipolar disorder, psychosis or anxiety spectrum disorders, respectively);
• current untreated alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine;
• for women, pregnant as determined by pregnancy screening, or breastfeeding; and 5) seeking (or undergoing) treatment for tobacco dependence or smoking.