Nicotine Differences in Smokers

Nicotine Discrimination in Smokers

The primary aim of this project is to determine the threshold dose of nicotine, which the smokers will be able to differentiate from placebo (saline). Will use IV pulsed-nicotine infusion that closely matches nicotine delivery by inhaled tobacco use (i.e., tobacco cigarette or electronic cigarette), allowing precise and reproducible nicotine delivery. Four nicotine doses (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) which are within the range of nicotine doses that are delivered by cigarettes with very low to regular nicotine content. These doses will be delivered as a cluster of 4 pulsed-nicotine infusions of 2 sec duration with a 28 sec interval between each dose.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Saline; Drug: 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine

Detailed Description

Twenty participants will have 2 Experimental Session on 2 separate days. Experimental Session 1 will determine if smokers can reliably discriminate 0.1mg nicotine/pulse nicotine from saline. Experimental Session 2 will determine if smokers can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline.

Hypothesis: The threshold for discrimination will be 0.05 mg nicotine/pulse and the doses below that (0.025, and 0.0125 mg nicotine/pulse) will be subthreshold.

Exploratory Aim: To explore the relationship between the threshold for subjective drug effects and drug discrimination.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Veterans Affairs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Female and male smokers, aged 18 to 65 years veterans and non-veterans who have been smoking tobacco cigarettes for at least a year
• smoke ≥ 5 cigs/day ;
• urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker (23)
• not seeking treatment at the time of the study for nicotine dependence
• Good health as verified by medical history, screening examination, and screening laboratory tests
• For women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion criteria:

• History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study
• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine
• use of e-cigarettes more than 10 days in the past 30 days
• urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

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; Experimental Session 2 will determine if smokers can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline.	Drug: Saline; Saline will be use to determine if smokers can discriminate from the nicotine/pulse of nicotine and saline
Placebo Comparator: saline; Saline will compared to different nicotine doses. Nicotine doses: 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline.	Drug: 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine; Determine if smokers can discriminate 0.05, 0.025, and 0.0125 mg nicotine/pulse of nicotine from saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Effect Questionnaire	Liking effect	over 3 hours

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D.,Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Actual): July 19, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: MS063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No