Smoking cessation: how effective are nicotine substitutes?

January 23 2009

Nicotine is generally regarded as the main component responsible for the addictive properties of tobacco. However, a CNRS and College de France research team directed by Jean Pol Tassin, Inserm research director, has just proved that nicotine alone is not sufficient to trigger tobacco-dependence in smokers. Other compounds in tobacco are essential to induce addiction. This discovery also explains why the nicotine substitutes used to aid smoking cessation are ineffective in the long-term. This study has just been published in the advanced on-line edition of the Journal of Neuroscience.

Nicotine is only addictive when it is associated with certain components of tobacco. This main result derived from the research carried out by Jean Pol Tassin is a new step forward in understanding the mechanisms of drug dependence.

During these last two years, this team of researchers showed that drugs such as cocaine, amphetamines, morphine, or alcohol cause a dissociation (or “uncoupling”) (1) between noradrenergic and serotoninergic neurons (2). The first are responsible for awareness of external events, the other for controlling impulses. Dependant persons feel environmental stimuli more intensely (including a desire for the product) and loose the capacity to control their impulses. Normally, these two neuronal circuits mutually control each other. However, the uncoupling between the two causes an imbalance which seems to be responsible for the addiction process and dependant persons are unable to check their craving for the product.

Nicotine, unlike other drugs, does not cause this decoupling. To try and understand why tobacco still has a very strong addictive power, the researchers investigated its other compounds. In this new study, the scientists proved that it is the combination of nicotine and other products contained in tobacco called monoamine oxidase (MAO) inhibitors that causes this decoupling. More precisely, they showed that MAO inhibitors enhanced the addictives properties of nicotine as they inhibit the action of a natural protection that serotoninergic neurons have with respect to nicotine: the serotoninergic 5-HT1A receptor. The effect of nicotine on serotonin release is so intense that “feedback control” blocking serotonin release occurs in a few fractions of a second. This “feedback control” phenomenon is only possible that when these 5-HT1A receptors play their protective role. Without this protection, serotoninergic neurons are activated by nicotine, they are uncoupled and trigger the addiction process.

“80% of nicotine patch users start to smoke again”. To conclude this study, the authors therefore explain why current smoking cessation therapies fail in a large number of cases. Candidate smoking cessation aids such as chewing-gums and patches are effective at the start of treatment, as long as the effects of MAO inhibitors persist. However, after several weeks of withdrawal, the absence of tobacco (and therefore MAO inhibitors), allows the return of natural protection. Nicotine alone is not sufficient as a replacement product.

For Jean Pol Tassin “These studies may help improve approaches to the treatment of nicotine dependence. They also question the efficacy of current tobacco replacement therapy and show why users of nicotine patches and chewing-gums start to smoke again after only a few weeks in more than 80% of cases. A new composition combining nicotine and products blocking the natural protection due to the 5-HT1A receptors would be a more effective tobacco substitute. This may be used in a new strategy in withdrawal therapy."

(1) Un nouveau mécanisme explicatif de la pharmacodépendance
(2) These neurons synthesize and release two neurotransmitters, noradrenaline or serotonin: the first helps control attention, emotions, sleep, dreaming and learning and the second has different functions such as the control of temperature, sleep, mood, appetite and pain.

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"Inhibition of Monoamine Oxidases Desensitizes 5-HT1A Autoreceptors and Allows Nicotine to Induce a Neurochemical and Behavioral Sensitization"

Christophe Lanteri,1,2 Sandra Jimena Hernandez Vallejo,2,3 Lucas Salomon,1,2 Emilie Lucie Doucet,1,2 Gerard Godeheu,1 Yvette Torrens,1 Vanessa Houades,1 and Jean-Pol Tassin1

(1) Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7148, Collège de France
(2) Université Pierre et Marie Curie, Université Paris 06, 75005 Paris, France
(3) Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S893, Equipe 9, Faculté de Médecine Pierre et Marie Curie, Site Saint-Antoine, 75012 Paris, France

Journal of Neuroscience, 21 January 2009

Researcher’s contact
Jean Pol Tassin
Phone: 33 1 44 27 12 31

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