Nicotine Metabolism and Low Nicotine Cigarettes

This study examines the effects of smoking low nicotine cigarettes on smoking behaviors and
toxin exposure in fast and slow nicotine metabolizing smokers. We will recruit current
smokers (split between slow and rapid nicotine metabolizing smokers) for a 35-day protocol.
Participants will smoke their own brand cigarettes during a baseline 5 day period, followed
by a 15-day period of smoking low nicotine content cigarette level 1: 0.25 mg nicotine
content, followed by a 15-day period of smoking low nicotine content cigarette level 2: 0.08
mg nicotine content. This application is designed to provide empirical science to inform the
FDA on the effect smoking low nicotine content cigarettes will have on use patterns and harm
exposure.

Inclusion Criteria:

1. adults age 21-65.

2. smoking at least 10 cigarettes per day.

3. smoking daily for the last 5 years.

4. Provide a baseline breath CO reading equal to or greater than 10 parts per million.

5. smoke predominantly non-menthol filtered cigarettes (research cigarettes are only
non-menthol).

6. not currently using any other nicotine containing products such as cigars, smokeless
tobacco, nicotine replacement therapies (patch or gum).

7. are fluent in English and are capable of providing written informed consent, which
includes compliance with the requirements and restrictions listed in the combined
consent and HIPAA form.

Participants who meet the inclusion/exclusion criteria and attend an Intake Visit for
medical screening will be asked to provide a blood sample to determine NMR. Only those
individuals who are characterized as slow or rapid, based on NMRs ≤ .26, or ≥ .42, will be
eligible.

Exclusion Criteria:

1. use of any nicotine containing products other than cigarettes

2. current or impending enrollment in smoking cessation program

3. history in the last year or current treatment of substance abuse (other than nicotine
dependence)

4. positive drug screen for cocaine, methamphetamines or opiates for urine drug screen at
intake session

5. alcohol use greater than 25 standard drinks per week

6. current or planned pregnancy or lactating

7. history or current diagnosis of psychosis, bipolar disorder, mania, or schizophrenia

8. current major depression (history of major depression but in remission for a minimum 6
months is eligible).

9. serious or unstable disease within past year (e.g. cancer other than melanoma, heart
disease)

10. history or current diagnosis of COPD

11. history of stroke or heart attack

12. age less than 21 years- We wish to recruit smokers with well established smoking
patterns and will restrict recruitment to those over 21

13. age more than 65 years - smoking is often associated with cardiovascular and pulmonary
obstructive diseases that manifest later in life. As smokers develop these problems,
smoking behavior and biomarkers of harm may be affected therefore we will restrict
enrollment to those under age 65

14. provide baseline CO reading less than 10 at initial session

15. current use (or use within past 14 days) of any medication that affects the
biotransformation of nicotine, such as anticonvulsant drugs, rifampin, and disulfiram;
or any psychoactive medications which can affect smoking behaviors

16. any conditions viewed by the PI or study physician as creating a potential increased
risk to a participant due to their participation will be reasons for exclusion

17. at the discretion of the PI, any participants viewed as non-compliant will be excluded
from further participation

18. Smoke cigarettes with a filter size other than standard or slim sized as the
topography mouthpieces are sized for standard filters and have an adapter for slim
cigarettes only.