Reduced Nicotine Cigarettes in Smokers With Mood and Anxiety Disorders

The overall aim of this project is to evaluate the effect of progressive nicotine reduction
in cigarettes on smoking behavior, toxin exposure and psychiatric symptoms in smokers with
comorbid mood and/or anxiety disorders.

To do so, we will randomly assign 200 adult smokers with a unipolar mood and/or anxiety
disorder within the past year to smoke research cigarettes that will contain either a) Usual
Nicotine Content (UNC): nicotine content similar to their preferred usual brand of
cigarettes, or b) Reduced Nicotine Content (RNC): nicotine content per cigarette is
progressively reduced from approximately 11.6 mg to 0.2 mg per cigarette over 18 weeks. All
subjects will participate in baseline periods prior to double-blind randomization to assess
normal smoking behavior and then to establish ability to tolerate research cigarettes prior
to randomization.

A total of 280 participants will be enrolled in the study at two sites with the aim of
randomizing 200 who complete the baseline phase. 100 participants will be enrolled in the
randomized phase at Penn State Hershey and 100 at the Massachusettes General Hospital site.
Participants will be started on the study protocol during Baseline I and Baseline II but will
be removed from the study if they are not able to comply with the protocol. We expect that
approximately 40 participants at each site drop out from the study prior to randomization
(due to inability to comply with study protocol).

It is our hypothesis that nicotine intake, as measured by plasma cotinine concentration, will
decline as a function of cigarette nicotine content in the RNC group. Further, it is our
hypothesis that by gradually reducing the nicotine content of the cigarettes in a step-wise
fashion, there will not be significant increases in biomarkers of tobacco smoke exposure,
severity of nicotine withdrawal symptoms, mood and anxiety symptomatology or protocol
non-adherence over time in the experimental group (RNC) as compared with the UNC control
group.

Inclusion Criteria:

- Smoke >4 cigarettes/day for at least a year

- No quit attempt in prior month

- Not planning to quit smoking within next 6 months

- Plan to live in local area for next 8 months

- Meet diagnostic criteria for a current or lifetime Anxiety Disorder or Mood Disorder
as determined by the Mini-international Neuropsychiatric Interview

- Read and write in English

- Women not pregnant or nursing and taking steps to avoid pregnancy

- Able to understand and consent to study procedures

Exclusion Criteria:

- Unstable or significant medical condition such as Chronic obstructive pulmonary
disease D or kidney failure

- Use of non-cigarette nicotine delivery product in the past week or smoking cessation
medicine in prior month

- Currently reducing or planning to reduce cigarette consumption in next month

- Uncontrolled serious psychotic illness or substance abuse or inpatient treatment for
these in the past 6 months

- Current suicide risk on clinical assessment

- Aged <18 or >65

- History of difficulty providing blood samples (fainting, poor venous access)

- Unwilling to remain on one flavor of cigarette (regular or menthol) for the duration
of the trial