title: Quitting cigarette smoking produces minimal loss of chronic tolerance to nicotine.
abstract: BACKGROUND
  Long-term exposure to nicotine is associated with chronic tolerance to its acute effects, adaptation that may lead to tobacco dependence. The time course for loss of this tolerance after cessation of exposure is not known in humans but could relate to risk of smoking relapse.
  
  
  OBJECTIVE
  We examined changes in responses to nicotine as a function of days, weeks, or years of smoking cessation in formerly dependent smokers to determine at what point sensitivity to nicotine is reinstated (i.e., loss of tolerance).
  
  
  METHODS
  Acute subjective, cardiovascular, performance, and reinforcing (self-administration) effects of nicotine nasal spray (0-20 microg/kg) were assessed prospectively in men and women smokers before and then day-by-day (study 1) or 3 weeks (study 2) after stopping smoking. A smoking resumption period (study 1) and a group of non-quitting smokers (study 2) were included to control for the passage of time. These effects were also compared cross-sectionally between those who had quit for 1-4 years and those who had for 6-19 years in a separate sample of long-time ex-smokers to determine whether lengthier abstinence causes greater loss of tolerance (study 3).
  
  
  RESULTS
  No clear loss of tolerance was observed on any measure in studies 1 or 2, suggesting that chronic tolerance is fully maintained for at least weeks after quitting smoking. Sensitivity to nicotine's effects was also not different as a function of years quit in study 3.
  
  
  CONCLUSIONS
  Chronic tolerance to nicotine is not lost within several weeks of quitting smoking and may not change even after years of abstinence from tobacco use.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. perkinska@msx.upmc.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Perkins
authors.forename: D
authors.initials: D
authors.lastname: Gerlach
authors.forename: M
authors.initials: M
authors.lastname: Broge
authors.forename: M
authors.initials: M
authors.lastname: Sanders
authors.forename: J
authors.initials: J
authors.lastname: Grobe
authors.forename: C
authors.initials: C
authors.lastname: Fonte
authors.forename: C
authors.initials: C
authors.lastname: Cherry
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Jacob
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000704:Analysis of Variance; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D011446:Prospective Studies; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000523:psychology; D016540:Smoking Cessation / Q000523:psychology*
chemical_list: D009538:Nicotine