Nicotine Reinforcement and Aversion in Young Adult Light Smokers
| Status: | Recruiting |
|---|---|
| Conditions: | Smoking Cessation, Psychiatric, Tobacco Consumers |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 30 |
| Updated: | 9/13/2018 |
| Start Date: | January 4, 2017 |
| End Date: | December 2020 |
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
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
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.
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.
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).
We found this trial at
1
site
West Haven, Connecticut 06516
Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D.
Phone: 203-937-4823
Click here to add this to my saved trials
