Effects of Quitting Study A Test of Pre-clinical Findings

Study design We will recruit until we have 70 current smokers who want to quit at two sites
(Univ of Vermont and Dartmouth Medical School). We will also recruit a comparison group of
70 long-time former smokers to assist in interpretation of the results. In the first week,
smokers will smoke their usual number of cigs/day. They will then quit and are to remain
abstinent for 4 weeks. We will use a schedule of escalating monetary contingencies based on
breath and saliva and/or urine samples to encourage abstinence. We will obtain dependent
measures twice/week. The primary measures of reward responsivity will be the percent
choosing the hard task and the amount of responding for a monetary reward on the EEfRT task
and the score on our Rewarding Events scale. Other outcomes will be delay discounting
results and self-reports of anhedonia and apathy.

The study will run for 1 week pre-cessation (2 visits) and then for 4 weeks post-cessation.
Measures and biochemical verifications will occur twice/wk. Former smokers will attend once
a wee for four weeks.

For the first week of abstinence, the cutoff for nonsmoking will be CO <8 ppm. For the
remaining weeks, abstinence will be verified with a score of 0 (<10 ng/ml of cotinine) on a
test strip in a saliva or urine sample plus a CO <8 ppm.

At the initial session, completion of baseline surveys will describe the sample and also
measure plausible moderators such as depression.

We believe the most direct test of reward sensitivity is an evaluation of the influence of
abstinence on operant responding for a reward. Thus, we have chosen performance on the
Effort Expenditure for Rewards Task (EEfRT), which examines responding as a function of
response cost, reward magnitude and probability of reward, as one of our primary outcomes.

For a self-report measure we will use our Rewarding Events (RE) scale that asks both about
occurrence of presumed rewarding events and their anticipated pleasantness. Our RE scale
will ask participants to rate 58 items on frequency in the last week as well
perceived/expected pleasantness of events.

Secondary measures include the 18-item Apathy Evaluation Scale (AES), the Temporal
Experience of Pleasure (TEPS), Minnesota Nicotine Withdrawal Scale-Revised (MNWS), and a
measure of delay discounting (DD).

Inclusion Criteria:

For all participants:

- 18 yrs old or older

- able to read and understand verbal English fluently

- citizen or resident alien

- agree to abstain from illegal drugs during the study

For current smokers:

1. currently smoke >10 cigarettes daily for > 1 yr

2. want to quit smoking for good via abrupt cessation without treatment

3. willing to quit 7-14 days from study entry and not reduce before quitting

4. no reduction in cigs/day by >25% in the last month

5. agree to no use of non-cigarette tobacco, non-tobacco nicotine, marijuana, illegal
drugs, electronic cigarettes, or smoking cessation medications during the study

6. have carbon monoxide (CO) level > or = 8 ppm at the time of consent

7. no current use of prescribed psychoactive medications, including smoking cessation
products.

For former smokers:

1. smoked >10 cigarettes daily for > 1 yr

2. quit at least 1 yr ago

3. use of cigarettes or e-cigarettes 5 or fewer times in past year

4. no tobacco or nicotine-containing product in last month

5. agree to no use of non-cigarette tobacco, non-tobacco nicotine, marijuana, illegal
drugs, electronic cigarettes, or smoking cessation medications during the study

6. have carbon monoxide (CO) level < 8 ppm at the time of consent

7. no current use of prescribed psychoactive medications, including smoking cessation
products.

Exclusion Criteria for all participants:

- History of hand or wrist problems that could be exacerbated by study participation or
interferes with completion of tasks

- current (last year) mood or alcohol/drug-related psychiatric disorder or any
neurological condition that could influence reward sensitivity; e.g. Parkinsonism

- used marijuana 2 or more times in the last month

- problems with the use of alcohol or illegal drugs in the last 6 months

- currently pregnant

- use of smokeless tobacco

- lacking the use of one or both hands