Addictive Threshold of Nicotine

June 9, 2026 updated by: Yale University
To determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, -and reinforcement in smokers with different levels of dependence.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this project is to determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, and reinforcement in smokers with different levels of dependence. Participants will have an Adaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline to be administered by the research staff.

Reinforcement will be assessed with the percentage of nicotine choices during the Choice trials. The discrimination is the percentage of correctly identified nicotine and saline infusions. Rewarding effects will be assessed with the "Pleasurable Effects" composite score of the Drug Effects Questionnaire (DEQ).

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • Recruiting
        • VA Healthcare System
        • Principal Investigator:
          • Mehmet Sofuoglu, M.D.,Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • to contact their primary care provider when necessary.
  • Adults, aged 21 to 59 years. Individuals less than 21 will be excluded because the minimum age for purchasing tobacco products is 21 in our state. The upper age is set at 59 because there are no previous IV nicotine studies that enrolled smokers over the age of 59.
  • 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 based on the level of dependence, assessed with the FTND scores (Heatherton et al. 1991) (low or no dependence 4 and moderate or high level of dependence 5.
  • 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
  • seeking (or undergoing) treatment for tobacco dependence or smoking.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nicotine
Adaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline (A or B).
Drug: Nicotine
Nicotine will be infused using a pump.
Other: Saline
Saline with be used to compare Nicotine, Saline will be infused using a pump
Placebo Comparator: saline
Subjects will have sample A and B, one being nicotine and one being saline. The doses will be blinded from PI, subject and staff. The subject must choose A or B for the next ten choices.
Drug: Nicotine
Nicotine will be infused using a pump.
Other: Saline
Saline with be used to compare Nicotine, Saline will be infused using a pump

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
correctly identifying nicotine
Time Frame: up to 8 weeks
Reinforcement will be assessed with the percentage of nicotine doses chosen during the Choice trials (out of 16), 4 choices per day over four days.
up to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2024

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

October 12, 2023

First Submitted That Met QC Criteria

October 17, 2023

First Posted (Actual)

October 24, 2023

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 9, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000036324
  • 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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