Background: There is a hypothesis that substances present in, or derived from, tobacco smoke inhibit monoamine oxidase (MAO) in the brains of smokers, reducing the degradation of catecholamine neurotransmitters involved in central reward pathways and acting synergistically with nicotine to increase its addictive effects.
Objective: The objective of this review was to evaluate the evidence for a role of MAO inhibition by tobacco-derived substances in tobacco dependence.
Investigational plan: Relevant studies on the effects of tobacco use on MAO levels or activity in humans were identified by electronic searches.
Results: The identified data show a clear association between smoking and lower density of MAO-A and MAO-B binding sites in the brains of smokers and strong evidence that MAO is inhibited by a substance or substances in, or derived from, tobacco smoke. There was little evidence to support the hypothesis that low MAO levels/activity is a predictive factor for tobacco use. Substances that inhibit MAO in in vitro assays have been isolated from tobacco leaves and tobacco smoke; however, no single substance has been shown to be absorbed from tobacco smoke and to inhibit MAO in the brains of human smokers. Nevertheless, it is possible that MAO inhibition in smokers could result from additive or synergistic effects of several tobacco-derived substances. MAO inhibition potentiates the reinforcing effects of intravenous nicotine in rodents; however, no data were identified to support the hypothesis that MAO inhibitors in or derived from tobacco or tobacco additives affect tobacco dependence in human smokers.
Implications: This comprehensive review describes the available evidence for the role of MAO inhibition in tobacco dependence and points the way for further research in this field. In view of the large number of MAO inhibitors identified in tobacco and tobacco smoke, identification of the putative inhibitors responsible for the lower level/activity of MAO in smokers may be impractical. Future studies must address whether the lower level/activity of MAO observed in smokers is also seen in users of other tobacco products and if this change is implicated in their dependence-inducing effects.
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