The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial

Abstract

Background: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders.

Methods: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine.

Results: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004).

Conclusion: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health.

Trial registration: TRN: NCT01928758, registered August 21, 2013.

Fig 1. CONSORT participant flow diagram.

Fig 2

2A-2D. Changes in plasma cotinine, exhaled CO, daily cigarette consumption, and FTND nicotine dependence score among completers (n = 143) smoking either Usual Nicotine Content (n = 74) cigarettes or Reduced Nicotine Content (n = 69) cigarettes. * indicates statistically significant between group difference at Visit 10, controlling for Visit 4 baseline.

Fig 3

3A-3D. Changes in OASIS, QIDS, PSS, and NNAL^# among completers (n = 143) smoking either Usual Nicotine Content (n = 74) cigarettes or Reduced Nicotine Content (n = 69) cigarettes. * indicates statistically significant between group difference at Visit 10, controlling for Visit 4 baseline. # urine NNAL measured in randomly selected subgroup (n = 26 on RNCs and n = 25 on UNCs, evenly stratified by site and by study group), who provided urine samples at randomization (v4) and at the end of the randomized phase of the trial (v10).

Fig 4. The proportion of participants initially randomized to reduced nicotine content or usual nicotine content cigarettes who had quit smoking cigarettes at visit 11, and at visit 12.

*p<0.01 for comparison between proportion randomized to RNC and UNC group who reported no cigarettes smoked in the previous week with exhaled CO<10ppm.