The purpose of this study is to determine the efficacy, acceptability and unintended
consequences of very low nicotine content cigarettes (VLNCC) in smokers with current or past
year substance use disorders (SUD). The primary aim of this study is to determine whether 6
weeks of VLNCC compared to normal nicotine content cigarettes (NNCC) will result in more
smoking cessation over 6 months and reduce cigarette use, cotinine, and biomarkers of
toxicity. We will also assess the effects of VLNCC versus NNCC cigarettes on frequency of
substance use and substance cravings (drugs and alcohol) because this is relevant to the
safety of these products among smokers with SUD. Secondary aims are to study effects on
cigarette craving, nicotine withdrawal and dependence, and depressed mood. Methods: Random
assignment to VLNCC versus NNCC of up to 312 smokers with SUD will be balanced by gender,
degree of tobacco dependence, and recent drug and alcohol use. All smokers will be provided
with smoking counseling. Assessments over 6 months will assess effects both during the 6
weeks of using research cigarettes and after return to usual cigarettes. The importance is in
determining the viability and safety of this public health strategy in terms of effects on
both smoking and other substance use in a highly addicted population, which is essential to
determine before the FDA implements this policy.