Nicotine and nonnicotine factors in cigarette addiction

Psychopharmacology (Berl). 2006 Mar;184(3-4):274-85. doi: 10.1007/s00213-005-0250-x. Epub 2005 Dec 16.


Rationale: A great deal of research supports the role of nicotine in cigarette addiction. However, the effectiveness of nicotine replacement therapy (NRT) as a smoking cessation treatment has fallen short of initial hopes. A key reason may be that NRT does not address nonnicotine components of smoking reinforcement. These include constituents that provide reinforcing sensory stimulation, components that minimize excessive irritation from inhaled nicotine and other pharmacologically active compounds in cigarette smoke.

Objective: Studies using various paradigms to dissociate nicotine from other components of smoking are summarized.

Results: Nonnicotine components provide many rewarding effects, often surpassing the direct effects of nicotine. Substitutes for the sensory effects of smoking may be effective in relieving craving for cigarettes and in facilitating smoking cessation. Moreover, techniques for devaluing smoking-related cues may decrease craving and enhance subsequent abstinence. Promising approaches for devaluing smoke cues include extinction-based treatments employing denicotinized cigarettes and the use of nicotinic agonist and/or antagonist treatment during the weeks leading up to a quit attempt. Recent studies suggest that incorporating these approaches into a treatment program may significantly increase smoking abstinence rates. Preliminary findings also suggest that replacement of the effects of monoamine oxidase inhibitors contained in cigarette smoke may enhance quit rates.

Conclusions: While current NRT methods have been the mainstay of smoking cessation treatment and will likely continue to serve a useful role, the next stage of progress will likely entail the development of tools designed with recognition of the importance of nonnicotine components of cigarette smoking.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Association Learning / drug effects
  • Cues
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Nicotine / administration & dosage*
  • Perception / drug effects
  • Sensation / drug effects
  • Smoking / psychology*
  • Smoking Cessation / psychology*
  • Tobacco Use Disorder / psychology*
  • Tobacco Use Disorder / rehabilitation
  • Treatment Outcome


  • Nicotine