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Nicotine Reinforcement and Aversion in Young Adult Light Smokers

This study is currently recruiting participants.
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Verified July 2017 by Mehmet Sofuoglu, Yale University
Information provided by (Responsible Party):
Mehmet Sofuoglu, Yale University Identifier:
First received: December 7, 2011
Last updated: July 12, 2017
Last verified: July 2017
The proposed study will examine the threshold for nicotine self-administration (NSA) using five different nicotine doses in young adult male and female non-dependent smokers (light and intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will enroll 195 individuals, targeting a total of 72 completers (36 male and 36 females). In each of the five experimental sessions, smokers will be randomly assigned to one of the five doses of nicotine (0.0125, 0.025, 0.05, 0.1 and 0.2 mg/70 kg). The highest dose, 0.2 mg/70 kg, corresponds to nicotine delivered by about one or two puffs of a cigarette. At the beginning of each experimental session, smokers will sample the assigned both the nicotine dose for that experimental session, and the placebo (saline) dose, followed by the opportunity to choose between nicotine and placebo for a total of ten choices over a 150-minute period. The main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration per unit change in nicotine dose). We will also collect measures of nicotine intake (cotinine), nicotine clearance (3-hydroxycotinine (3-HC) / cotinine), and self-report drug effects

Condition Intervention
Nicotine Addiction Drug: Saline Drug: Nicotine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Nicotine Reinforcement and Aversion in Young Adult Light Smokers

Resource links provided by NLM:

Further study details as provided by Mehmet Sofuoglu, Yale University:

Primary Outcome Measures:
  • DEQ [ Time Frame: 3 years to complete ]
    ratings DEQ among smokers

Estimated Enrollment: 64
Actual Study Start Date: January 4, 2017
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nicotine
subjects will be randomly assigned to one of the five doses of nicotine (0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg). At the beginning of each experimental session, subjects will first sample the assigned nicotine dose and placebo (saline) condition that are randomly labeled as A or B. which may be nicotine or saline. This procedure will allow subjects to sample the nicotine and saline that will be available during that session. In addition, subjective and physiological responses to the sample nicotine dose and saline will be assessed.
Drug: Nicotine
(0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg).
Other Name: IV nicotine
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: Saline
5cc's of saline give at least once.
Other Name: Placebo

Detailed Description:

Aim #1: To assess the threshold reinforcing dose and dose-effect curve for IV NSA at low doses in young adult LITS.

Hypothesis #1A: The threshold reinforcing doses for IV NSA will be between 0.0125 to 0.1 mg/70 kg.

Hypothesis #1B: The dose-effect curve for NSA will differ between males and females with relatively flat curve in female smokers.

Aim #2: To assess the threshold and dose-effect curve for the positive and negative/aversive subjective effects of IV nicotine at low doses and its relationship to nicotine reinforcement.

Hypothesis #2 A: The threshold for the positive effects will be between 0.0125 to 0.1 mg/70 kg, for the negative/aversive effect it will be ≥ 0.1 mg/70 kg.

Hypothesis #2B: Nicotine reinforcement will be positively correlated with the positive and negatively correlated with the negative/aversive subjective effects of IV nicotine.

Exploratory Aims: To examine the influence of nicotine clearance rate on nicotine reinforcement threshold and dose-effect curve.


Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria: 1) Female and male smokers, aged 18 to30 years, who have been smoking for at least a year, and a life-time consumption of at least 100 cigarettes; 2) smoke more frequently than once a week and ≤5 cpd; 3) FTND score <3 indicating no or minimal evidence for nicotine dependence; 4) urine cotinine levels >100 ng/mL indicating smoking status and a level <1000 mg/mL consistent with nicotine intake of LITS; 5) not seeking treatment at the time of the study for nicotine dependence; 6) in good health as verified by medical history, screening examination, and screening laboratory tests; 7) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion criteria: 1) history of major medical illnesses that the physician investigator deems as contraindicated for the subject to be in the study; 2) requirement of any form of regular psychotropic medication (antidepressants, antipsychotics, or anxiolytics) or psychiatric diagnosis and treatment for psychiatric disorders including major depression, bipolar disorder, schizophrenia in the past 6 months; and 3) current dependence to alcohol or any other recreational or prescription drugs and; 4) daily use of smokeless tobacco products or exclusive daily use of e-cigarettes (non-daily users will be included).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01495819

United States, Connecticut
Department of Veterans Affairs Recruiting
West Haven, Connecticut, United States, 06516
Contact: Lance Barnes    203-937-4823   
Contact: Marcedes Coffman, M.A.    203-932-5711 ext 4841   
Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.         
Sponsors and Collaborators
Yale University
Principal Investigator: Mehmet Sofuoglu, M.D,Ph.D. Yale University
  More Information

Responsible Party: Mehmet Sofuoglu, Principle Investigator, Yale University Identifier: NCT01495819     History of Changes
Other Study ID Numbers: 1010007514
Study First Received: December 7, 2011
Last Updated: July 12, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Mehmet Sofuoglu, Yale University:
vitals associated with smoking

Additional relevant MeSH terms:
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action processed this record on September 19, 2017