Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.