New Research Sheds Light On Why It's So Hard To Quit Smoking

New research suggests that certain people may be genetically predisposed to find it harder to quit smoking. StepanPopov/Shutterstock

Kicking the habit of smoking is not always an easy thing to do, although prospective quitters may be interested to hear about a recent flurry of research into the science of cigarettes, which could help reveal new pathways for overcoming their addictiveness. Over the past few days, two studies regarding the effects of nicotine have been published, both of which could have implications for those wishing to devise appropriate quitting strategies.

The first of these appeared in the journal eLife, and sheds new light on the ways in which two neurotransmitters, glutamate and acetylcholine, interact in order to generate nicotine dependence. Both have previously been identified as key players in this process. For instance, acetylcholine plays a role in the regulation of heart rate and physical arousal, and is mimicked by nicotine, which binds to acetylcholine receptors. Glutamate, meanwhile, has been noted for its role in driving drug-seeking behavior in animal studies involving a number of different addictive substances.

Researchers from the Laboratory of Molecular Biology at The Rockefeller University genetically engineered mice so that they were unable to synthesize acetylcholine in a region of the brain known as the habenula. As a consequence, they noted a significant decrease in glutamate transmission between nerve cells in these mice, which were subsequently found to be resistant to nicotine dependence.

This suggests that acetylcholine may regulate glutamate transmission, indicating that if acetylcholine levels can be manipulated, nicotine dependency could be avoided.

A second paper, which appeared on the same day in the journal Translational Psychiatry, may contain clues as to why some people find it much harder to quit smoking than others. The study reviewed the results of 23 previous scientific investigations into nicotine addiction and smoking cessation, involving a total of 11,075 participants. Since dopamine is known to play a major role in substance dependence by activating the brain’s reward centers, researchers sought to determine if variations in the genes involved in dopamine synthesis might influence the addiction process.

They noticed a clear correlation between the presence of certain genes and the difficulty with which people were able to terminate their habit – although this pattern was only observed in Caucasian subjects, and did not apply to those of other ethnicities. The gene involved was DRD2/ANKK1, which regulates the density and availability of dopamine, and exists in a number of different variations. The team found that roughly two-thirds of white smokers had the A2/A2 form of this gene, while the remainder had either A1/A1 or A2/A2.

By extracting data from the 23 studies under investigation, the researchers discovered that, on the whole, those with the A2/A2 variation of the gene were considerably more likely to quit smoking and remain abstinent for a period of up to 12 months. However, the study authors also concede that, since relapse can occur at any point after this time period, it may not be possible to say categorically that a person has quit smoking for good.

Regardless, New Scientist reports that the team behind the study insist that their results can be used to help people tailor their attempts to give up smoking depending on their genetic makeup. For instance, those who carry the A1/A1 or A1/A2 forms of the gene may wish to consider “more aggressive strategies” than those with the A2/A2 form.

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