Impact of Sweeteners on the Addictive Threshold of Nicotine

To determine if sucralose, an artificial sweetener, modulates nicotine threshold doses for discrimination, subjective-rewarding effects, and reinforcement in smokers with varying levels of dependence.

Study Overview

• Status: Not yet recruiting
• Conditions: Smoking ( Cigarette)
• Intervention / Treatment: Drug: Nicotine 0.05 mg/pulse and 0.1 mg/pulse; Drug: Saline Placebo (0.5mL injection); Dietary supplement: sucralose; Dietary supplement: Sugar syrup (Placebo)

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mehmet Sofuoglu, M.D., Ph.D.; Phone Number: 203-932-5711; Email: Mehmet.Sofuoglu@yale.edu
• Study Contact Backup: Name: Stacy A Minnix, B.S.; Phone Number: 203--932-5711

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicotine; These test days will evaluate two nicotine doses (0.05 mg/pulse and 0.1 mg/pulse)	Drug: Nicotine 0.05 mg/pulse and 0.1 mg/pulse; Nicotine will be used and compared to saline given by IV push by study physician
Placebo Comparator: saline; Saline (sugar water)	Drug: Saline Placebo (0.5mL injection); Saline will be used compared to the low dose of Nicotine given by IV push by study physician
Placebo Comparator: unsweetened flavor; participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors	Dietary supplement: Sugar syrup (Placebo); Unsweetened flavor compared to the sweetened flavor sucralose.
Active Comparator: sucralose; participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors	Dietary supplement: sucralose; sweet flavor (sucralose) compared to unsweetened flavor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Discrimination Scale (DDS) score.	This scale asks the participants to select if they received Drug A or B and how confident they are in their selection on a scale of 0 to 10. Higher scores indicate more confidence.	OnTest Days 1, 2, 3 and 4
Drug Effects Questionnaire (DEQ) pleasurable effects score	The DEQ pleasurable effects consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.	OnTest Days 1, 2, 3 and 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Nicotine Withdrawal Scale score	This 8-item scale will be used to assess DSM-IV symptoms of nicotine withdrawal. Total score range 0-32. Higher scores indicate more severe withdrawal symptoms.	OnTest Days 1, 2, 3 and 4

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 13, 2026
• First Submitted That Met QC Criteria: August 13, 2026
• First Posted (Actual): August 18, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Smoking; Tobacco Smoking; Tobacco Use; Cigarette Smoking; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Drug Administration Routes; Drug Therapy; Circulatory and Respiratory Physiological Phenomena; Alkaloids; Solanaceous Alkaloids; Hemodynamics; Cardiovascular Physiological Phenomena; Nicotine; Injections; trichlorosucrose; Pulse
• Other Study ID Numbers: 2000043445; 2U54DA036151-11 (U.S. NIH Grant/Contract: NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No