Addictive Threshold of Nicotine

To determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, -and reinforcement in smokers with different levels of dependence.

Study Overview

• Status: Completed
• Conditions: Smoking Addiction
• Intervention / Treatment: Drug: Nicotine; Other: Saline

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 (Actual): 34
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Healthcare System

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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	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

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Actual): March 27, 2026
• Study Completion (Actual): March 27, 2026

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): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Solanaceous Alkaloids; Chlorides; Hydrochloric Acid; Nicotine; Sodium Chloride
• 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