Effects of reduced nicotine content cigarettes on individual withdrawal symptoms over time and during abstinence

Exp Clin Psychopharmacol. 2018 Jun;26(3):223-232. doi: 10.1037/pha0000179. Epub 2018 Mar 5.


In the United States, the Food and Drug Administration (FDA) has initiated a public dialogue about reducing the nicotine content of cigarettes. A reduced-nicotine standard could increase withdrawal symptoms among current smokers. We examined the impact of switching smokers to cigarettes that varied in nicotine content on withdrawal symptoms over 6 weeks. A secondary analysis (N = 839) of a 10-site, double-blind clinical trial of nontreatment-seeking smokers was completed. Participants were instructed to smoke study cigarettes, containing 0.4 to 15.8 mg of nicotine/g of tobacco, for 6 weeks and were then abstinent overnight. Using latent growth curves, trajectories of individual withdrawal symptoms were compared between the reduced nicotine content (RNC) conditions and a normal nicotine content (NNC) condition. Path analyses compared symptoms after overnight abstinence. Relative to NNC cigarettes, participants smoking RNC cigarettes had increased anger/irritability/frustration and increased appetite/weight gain during the initial weeks, but the symptoms resolved by Week 6. Individuals who were biochemically verified as adherent with using only the 0.4 mg/g cigarettes had higher sadness levels (Cohen's d = .40) at Week 6 compared with the NNC condition, although symptoms were mild. After a post-Week 6 overnight abstinence challenge, some RNC conditions relative to NNC condition exhibited reduced withdrawal. Individuals who were biochemically confirmed as adherent to the lowest nicotine condition experienced only mild and transient symptom elevations. Thus, a reduced-nicotine standard for cigarettes produced a relatively mild and temporary increase in withdrawal among nontreatment-seeking smokers (ClinicalTrials.gov No. NCT01681875). (PsycINFO Database Record

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cigarette Smoking / epidemiology
  • Cigarette Smoking / psychology*
  • Cigarette Smoking / trends*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotine / chemistry
  • Self Report
  • Smoking Cessation / methods
  • Smoking Cessation / psychology*
  • Substance Withdrawal Syndrome / diagnosis*
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / psychology*
  • Tobacco Use Disorder / diagnosis
  • Tobacco Use Disorder / epidemiology
  • Tobacco Use Disorder / psychology
  • Weight Gain / drug effects
  • Weight Gain / physiology


  • Nicotine

Associated data

  • ClinicalTrials.gov/NCT01681875