https://www.selleckchem.com/products/at-406.html This study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels. To examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage. These 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifyi score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other. These findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation. ClinicalTrials.gov Identifiers NCT02232737, NCT02250664, NCT02250534. ClinicalTrials.gov Identifiers NCT02232737, NCT02250664, NCT02250534. Mortality rates used to evaluate and improve the quality of hospital care are adjusted for comorbidity and disease severity. Comorbidity measured by International Classification of Diseases codes do not reflect the severity of the medical condition that requires clinical assessments not available in electronic databases, and/or laboratory data with clinically relevant ranges to permit extrapolation from o