Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
| Status: | Completed |
|---|---|
| Conditions: | Smoking Cessation, Tobacco Consumers |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/21/2016 |
| Start Date: | July 2012 |
| End Date: | August 2015 |
The purpose of the study is to learn more about tobacco dependence and nicotine metabolism
in African-Americans and whites, by studying to see if how fast a person metabolizes
nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent
they are on smoking cigarettes. The investigators believe that people with a faster rate of
metabolism may have more severe nicotine withdrawal symptoms and also may have a harder time
trying to quit smoking.
in African-Americans and whites, by studying to see if how fast a person metabolizes
nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent
they are on smoking cigarettes. The investigators believe that people with a faster rate of
metabolism may have more severe nicotine withdrawal symptoms and also may have a harder time
trying to quit smoking.
Our studies will use the nicotine metabolite ratio (NMR) (the ratio between the nicotine
metabolites 3'hydroxycotinine and cotinine)as a simple and clinically feasible biomarker for
the rate of nicotine metabolism. The investigators hypothesize that a faster rate of
metabolism leads to faster elimination of nicotine from the body and a more rapid
dissipation of brain tolerance to nicotine in the interval between cigarettes, leading in
turn to (1) more severe nicotine withdrawal symptoms and (2) greater subjective reward from
the cigarette smoked following deprivation. These effects would help to explain why smokers
with faster rates of nicotine metabolism have a poorer response to smoking cessation therapy
when compared to those with slower rates of metabolism.
The investigators will explore the relationship of the NMR to the endophenotypes of
withdrawal, craving and reward, with the assumption that these factors are likely
intermediaries for the mechanism linking nicotine metabolism to tobacco dependence and
smoking cessation rates with pharmacotherapy. Our study design uses a brief (6 hour)
interval of smoking abstinence followed by a "reward" cigarette to elicit the subjective
responses relating to withdrawal and reward. Because smoking behavior and severity of
nicotine dependence vary by race and sex the investigators will also compare the
relationship between NMR and withdrawal and reward in African American vs white smokers and
in men vs women.
Secondary analyses will examine whether nicotine half-life mediates the observed effects of
NMR on primary response measures.
metabolites 3'hydroxycotinine and cotinine)as a simple and clinically feasible biomarker for
the rate of nicotine metabolism. The investigators hypothesize that a faster rate of
metabolism leads to faster elimination of nicotine from the body and a more rapid
dissipation of brain tolerance to nicotine in the interval between cigarettes, leading in
turn to (1) more severe nicotine withdrawal symptoms and (2) greater subjective reward from
the cigarette smoked following deprivation. These effects would help to explain why smokers
with faster rates of nicotine metabolism have a poorer response to smoking cessation therapy
when compared to those with slower rates of metabolism.
The investigators will explore the relationship of the NMR to the endophenotypes of
withdrawal, craving and reward, with the assumption that these factors are likely
intermediaries for the mechanism linking nicotine metabolism to tobacco dependence and
smoking cessation rates with pharmacotherapy. Our study design uses a brief (6 hour)
interval of smoking abstinence followed by a "reward" cigarette to elicit the subjective
responses relating to withdrawal and reward. Because smoking behavior and severity of
nicotine dependence vary by race and sex the investigators will also compare the
relationship between NMR and withdrawal and reward in African American vs white smokers and
in men vs women.
Secondary analyses will examine whether nicotine half-life mediates the observed effects of
NMR on primary response measures.
Inclusion Criteria:
- African-American or Caucasian
- Age 18-70 years
- Regular smoker of 5 or more cigarettes per day
- Saliva cotinine of 100 ng/ml or greater
Exclusion Criteria:
- Obese (BMI > 38) or underweight (BMI < 17)
- Major systemic or psychiatric condition
- Medications that are inducers of CYP2A6
- History of alcohol abuse
- Positive drug urine tox test
- Pregnancy or breast feeding
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