A Smoking Intervention Study Using Scheduled Gradual Reduction With Varenicline to Help With Cessation

Smoking remains an intransigent public health concern. There is ample evidence that
non-pharmacological factors, such as environmental triggers (e.g., sight or smell of a
cigarette), can give rise to strong classically-conditioned urges to smoke (termed
'cue-reactivity' [CR]), and that exposure to smoking cues can contribute to cessation
failure. One promising intervention that may address CR is scheduled smoking with gradual
reduction (SGR). Under SGR, individuals smoke only at fixed intervals, and over several
weeks, systematically decrease their cigarettes consumed each day. The approach is
postulated to: 1) provide 'practice' coping with environmentally-triggered cravings that
occur during the inter-cigarette intervals, yielding increased self-efficacy to quit, and 2)
weaken the associations between cues and smoking. Accumulating evidence has also shown that
the smoking cessation drug, varenicline (VN), substantially ameliorates cravings and
enhances cessation, significantly outperforming other drugs. Interestingly, recent animal
research suggests that VN may operate at least partially by dampening conditioned drug
cravings. A combination therapy consisting of SGR+VN might thus lead to significantly
enhanced cessation, simultaneously attacking cravings using both pharmacological and
non-pharmacological approaches. Because the beneficial effects of SGR and VN may be at least
partially due to enhanced management of conditioned cravings, it is possible that that they
will be particularly efficacious for smokers with high levels of CR. Using both laboratory
experimental techniques and a prospective intervention design in this R34 application, we
propose to provide initial data to: 1) test the hypothesis that a combination of SGR+VN will
enhance cessation, 2) explore the possibility that SGR and VN might be particularly
efficacious among smokers with higher levels of CR, and 3) explore potential mechanisms
underlying treatment effects. Findings from this study would set the stage for larger
efficacy and effectiveness trials of SGR alone and in conjunction with VN, as well as
efforts to target SGR and/or VN toward the subgroups that would benefit the most (e.g.,
smokers with high levels of CR, carriers of specific smoking-related genotypes).

Inclusion Criteria:

- Current cigarette smoker

- Averages at least 10 cigarettes/day for 5 or more years

- DSM-IV diagnosis of Nicotine Dependence

- Breath carbon monoxide > 6 ppm

- Motivated to quit: score > 8 on Contemplation Ladder

- Age > 18 years

Exclusion Criteria:

- Current illicit substance use

- Other tobacco use (e.g., cigar, pipe)

- History of psychosis

- Past or current cardiovascular disease

- Impaired renal functioning

- Pregnancy

- Nursing

- Current treatment for smoking cessation

- Clinically significant depressive symptoms (CES-D > 16)

- Current suicidal ideation