What Nicotine Does to the Brain, and the Science of Smoking Cessation
By William Pollard
According to the Centers for Disease Control and Prevention, success rates for cessation remain low, with only 7.5% of smokers managing to quit smoking entirely. The need to increase motivation levels and help smokers quit is a popular topic among health authorities — especially in recent years after active smokers were found to be at higher risk of COVID–19 deaths (Patanavanich et al., 2023). This emphasizes the urgency of addressing cigarette addiction as the general population becomes more vulnerable to infectious diseases.
Quitting remains a struggle even for smokers who understand the harmful effects of smoking because there are physiological factors driving its addictiveness. Let’s discuss this more thoroughly below.
Quitting remains a struggle even for smokers who understand the harmful effects of smoking because there are physiological factors driving its addictiveness.
Nicotine and the brain
The smoke produced by cigarettes contains formaldehyde, lead, ammonia, hydrogen cyanide, arsenic, and nicotine, among 7,000 other chemicals. A 2020 article from Neuropharmacology explains how nicotine activates specific receptors found in our peripheral and central nervous systems, called nicotinic acetylcholine (nACh) receptors (Wittenberg et al., 2020). When nicotine binds to nACh receptors after the inhalation of cigarette smoke, these receptors trigger acetylcholine release.
This makes users feel a buzz that boosts feelings of alertness and focus. Balkan and Pogum (2018) further explain that nACh receptors are expressed abundantly in the hypothalamus, stimulating the dopaminergic system and cholinergic neurons. This simultaneously bombards the brain with stronger concentrations of the stress hormone, cortisol, and the pleasure hormone, dopamine.
However, continued smoking can eventually lead to harmful levels of serotonin, dopamine, glutamate, and other neurotransmitters in the brain, which can eventually affect mood regulation and a person’s response to stress (Chaplin, 2021). When the rush of dopamine wears off, the brain associates its drop with severe feelings of anxiety and stress as elevated levels of cortisol linger in the body. This creates a cycle where users become more dependent on the source of their anxiety, smoking, in order to rid themselves of it temporarily.
…this creates a cycle where users become more dependent on the source of their anxiety, smoking, in order to rid themselves of it temporarily.
Otherwise, nicotine is well known to have serious somatic side effects in addition to being highly addictive. The chemical makes blood vessels narrow, which could reduce blood flow across the body, including to the brain. This is why nicotine causes headaches among chronic users (Sam, 2023). Research by LaRowe and Ditre (2020) explains that the nACh receptors modulate pain sensitivity in acutely abstinent tobacco smokers, and constant exposure to nicotine may therefore cause your pain receptors to become more sensitive over time. Headaches could thus become a regular side effect or even a prelude to a more severe problem, such as neuron degeneration or the thinning of the cerebral cortex in the brain, according to Brooks and Henderson (2021).
The science of cessation
The CDC estimates that approximately 30% to 50% of US smokers attempt to quit in any given year. To cater to this demand, health authorities have developed nicotine replacement therapies (NRTs), which nearly double the chances of quitting smoking, according to the American Cancer Society.
In smoking cessation, NRTs are used to slowly wean users off their dependence on nicotine. This is done by replacing cigarettes — thereby cutting off the user from the many other harmful chemicals associated with tobacco — with a tobacco-free alternative that contains nicotine in smaller, controlled amounts. Users start using NRTs with a dosage that is closest to their current intake of nicotine, which is then decreased in minuscule intervals.
In smoking cessation, NRTs are used to slowly wean users off their dependence on nicotine.
Throughout this process, nACh receptors are activated in smaller amounts each time. The brain becomes acclimated once again to functioning on and releasing regular amounts of dopamine in the body without the need for foreign chemicals. Meanwhile, because their nicotinic cravings are still being satisfied, users can more successfully overcome withdrawal symptoms. This has been tested by the team of Yasmin Zakiniaeiz and colleagues (2020), who found that the nicotine patch reduces striatal smoking-induced dopamine release compared to a placebo patch. This confirms that NRTs directly affect the brain’s reward centers by making the act of smoking less rewarding over time and, therefore, making it easier for chronic smokers to quit.
Today, NRTs come in multiple forms to cater to different user preferences and to help individuals associate the process of cessation with more pleasurable experiences. This can mean differences in how nicotine is delivered — coming in multiple formats like gums, patches, or even inhalers — or different flavors for oral NRTs, with all sorts of fruity and minty variations available on the market.
If you attempt smoking cessation, it is best to first consult with your healthcare provider in order to determine the most effective NRT for your lifestyle and maximize your chances of success.
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Written by William Pollard
Edited by Lauren Wagner
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References
Balkan, B., Pogun, S. (2018). Nicotinic Cholinergic System in the Hypothalamus Modulates the Activity of the Hypothalamic Neuropeptides During the Stress Response. Current Neuropharmacology,16(4), 371-387. https://doi.org/10.2174/1570159X15666170720092442
Brooks, A.C., Henderson, B.J. (2021). Systematic Review of Nicotine Exposure’s Effects on Neural Stem and Progenitor Cells. Brain Sciences, 11(2), 172. https://doi.org/10.3390/brainsci11020172
Chaplin, A. (2021). Depression: The Role of Chronic Inflammation. Retrieved from https://knowingneurons.com/blog/2021/07/05/depression-the-role-of-chronic-inflammation/
LaRowe, L.R., Ditre, J.W. (2020). Pain, nicotine, and tobacco smoking: current state of the science. Pain, 161(8), 1688-1693. https://doi.org/10.1097/j.pain.0000000000001874
Patanavanich, R., et al. (2023). Active Smokers Are at Higher Risk of COVID-19 Death: A Systematic Review and Meta-analysis. Nicotine & Tobacco Research, 25(2), 177-184. https://doi.org/10.1093/ntr/ntac085
Sam. (2023). Does Nicotine Use Lead to Headaches? Retrieved from https://prilla.com/us/blog/does-nicotine-use-lead-to-headaches
Wittenberg, R.E., et al. (2020). Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction. Neuropharmacology, 177. https://doi.org/10.1016/j.neuropharm.2020.108256
Zakiniaeiz, Y. et.al. (2020). Nicotine patch reduces striatal smoking-induced dopamine release compared to placebo patch. Journal of Nuclear Medicine, 61(1). https://jnm.snmjournals.org/content/61/supplement_1/1566/tab-article-info
