According to Health Canada, approximately 37,000 deaths each year in Canada can be attributed to tobacco use, racking up $4.4 billion in hospital bills. Although the adverse health effects of smoking are well-known—thanks in part to the government’s anti-smoking campaigns—many have difficulty quitting, despite a variety of available cessation drugs. New research demonstrates that this may have to do with smokers’ genetics.
A recent study at the Montreal Neurological Institute and Hospital (the Neuro) focuses on the role that genetics play in the ability to stop smoking, and that information can be used to help more people quit successfully. It is well established that nicotine is the driving agent in smoking addictions. Studies have shown that smokers can be grouped into two genetic categories: those who metabolize nicotine quickly, and those who metabolize it slowly.
Dr. Alain Dagher, a McGill researcher at the Neuro, is among those examining the implications of these genetic traits of smokers. A recent experiment he conducted sought to highlight the differences in response between fast and slow nicotine metabolizers, and how this variability could play a role in an individual’s struggle to quit smoking.
Nicotine is believed to work through the brain’s reward pathway. The reward pathway is the body’s way of encouraging good evolutionary behaviour. Activities like eating or having sex trigger the release of chemicals in the brain that give us a feeling of pleasure. Nicotine causes the brain to release the same chemicals.
A fast nicotine metabolism is characterized by a surge in blood nicotine level after smoking a cigarette; this is fleeting, and nicotine levels begin to normalize within minutes. A slow metabolism means nicotine levels stay constant throughout the day. Slow metabolizers have a mutation in the enzyme that breaks down nicotine; this means their body is less efficient at breaking down the chemical compound.
Fast metabolizers become conditioned to this pleasure hit over time, and their brain associates nicotine surges with cigarettes. The close association renders this subset of the smoking population more reactive to smoking cues, such as images of cigarettes.
However, in the case of slow metabolizers, “there is never an explicit pairing in the brain between smoking and nicotine levels” Dagher said, because the nicotine levels stay constant. This variability between these two genetic pools of smokers means different cues drive them to reach for a cigarette.
Dagher tested this hypothesis by exposing each metabolic group to a smoking video and measured participants’ brains’ response through a functional MRI. He found that fast metabolizers’ brains had more active responses to cigarette cues than those of slow metabolizers. The more intense the brain’s response to smoking cues, the less likely that a smoker will be able to quit successfully.
The image of a cigarette or a person smoking is therefore more likely to trigger the desire to smoke in a fast metabolizer, while the slow
metabolizer’s desire would stem from withdrawal symptoms when nicotine levels fall below a certain threshold.
Thus, fast metabolizers are more likely to relapse when exposed to smoking situations. These include exposure to images of cigarettes and stressful situations. In addition, fast metabolizers are unlikely to benefit from the majority of cessation products, such as Nicorette, which work by providing a slow release of nicotine into the blood stream.
“[Fast metabolizers] might benefit from behavioral therapy, where they learn how to deal with their cravings,” Dagher said.
Conversely, slow metabolizers, who smoke to maintain nicotine levels, might find cessation products helpful in their quest to quit.
Dagher believes that the future of smoking cessation involves tailoring a quitting regime to a patient’s genome. Identifying how they metabolize nicotine will help quitters succeed. According to Dagher, the nicotine metabolizing enzyme is “easy to test for, the test just isn’t widely available.”
