Addiction & Criminology

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Short Communication - Addiction & Criminology (2025) Volume 8, Issue 2

Genetic Variations in Nicotine Metabolism: Why Some People Smoke More

Qiuda Thai *

Queensland Alliance for Environmental Health Sciences, The University of Queensland, Australia

*Corresponding Author:
Qiuda Thai
Queensland Alliance for Environmental Health Sciences, The University of Queensland, Australia
E-mail: q.thai@uq.edu.au

Received: 03-Mar -2025, Manuscript No. AARA-25-163809; Editor assigned: 04-Mar-2025, PreQC No. AARA-25-163809 (PQ); Reviewed:18-Mar-2024, QC No. AARA-25-163809; Revised:23-Mar-2025, Manuscript No. AARA-25-163809 (R); Published:30-Mar-2025, DOI:10.35841/aara-8.2.260

Citation: Thai Q. Genetic variations in nicotine metabolism: Why some people smoke more. Addict Criminol.2025;8(2):260

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Introduction

Nicotine addiction varies significantly among individuals, with some people smoking heavily while others are light or occasional smokers. While environmental factors such as peer influence and stress contribute to smoking behaviors, genetic variations in nicotine metabolism play a crucial role in determining how quickly nicotine is processed and how addictive it becomes. The enzyme cytochrome P450 2A6 (CYP2A6) is primarily responsible for nicotine metabolism, and differences in the CYP2A6 gene affect smoking intensity, addiction levels, and the ability to quit. Understanding these genetic variations can help in designing personalized smoking cessation programs and improving public health strategies [1].

When a person smokes, nicotine is rapidly absorbed into the bloodstream and travels to the brain, where it stimulates the release of dopamine, reinforcing the pleasurable effects of smoking. Nicotine is then metabolized in the liver, primarily by CYP2A6, into cotinine, which is further broken down into trans-3′-hydroxycotinine (3HC) before being excreted in urine [2].

The nicotine metabolite ratio (NMR) the ratio of 3HC to cotinine—indicates the speed of nicotine metabolism. High NMR (Fast Metabolizers): These individuals break down nicotine quickly, leading to shorter nicotine effects and stronger cravings, which result in higher cigarette consumption [3].

Low NMR (Slow Metabolizers): Nicotine remains in the system longer, reducing the need for frequent smoking, making them less prone to heavy smoking. Individuals with a fully functional CYP2A6 gene metabolize nicotine rapidly, leading to higher smoking intensity. They tend to smoke more cigarettes per day to maintain nicotine levels, making them more nicotine-dependent [4].

Those with defective or partially active CYP2A6 variants metabolize nicotine more slowly. As a result, they experience prolonged nicotine effects, leading to lower cigarette consumption and higher success rates in quitting [5].

Some people have partial or complete deletions of the CYP2A6 gene, significantly reducing their ability to metabolize nicotine. Individuals with these mutations often find smoking unpleasant and are less likely to become habitual smokers. These genetic differences explain why some individuals naturally avoid smoking or smoke less frequently [6].

CYP2A6 genetic variations are not evenly distributed across populations: East Asians (Chinese, Japanese, Korean populations) tend to have a higher prevalence of slow-metabolizing CYP2A6 variants, leading to lower smoking rates [7].

Europeans and Africans have a higher proportion of fast-metabolizing CYP2A6 variants, making them more susceptible to smoking-related health risks. Because nicotine metabolism influences smoking behavior, it also affects how individuals respond to smoking cessation treatments: Fast metabolizers often struggle with standard nicotine patches or gum because nicotine clears too quickly from their system. They may need higher doses of nicotine replacement therapy or alternative medications like varenicline (Chantix) to quit successfully [8].

Slow metabolizers respond better to NRT as nicotine stays in their system longer, making lower doses of nicotine patches or lozenges more effective. Bupropion (Zyban) works better for slow metabolizers because their nicotine levels remain stable, allowing them to control cravings more effectively [9].

Varenicline (Chantix) is more effective for fast metabolizers since it directly targets nicotine receptors, reducing cravings and withdrawal symptoms. Given the strong genetic influence on smoking behavior, genetic testing for CYP2A6 variants could help healthcare providers develop personalized smoking cessation plans. A precision medicine approach could: Identify whether a smoker is a fast or slow metabolizer. Recommend appropriate nicotine replacement doses or alternative medications [10].

conclusion

Genetic variations in nicotine metabolism, particularly those related to the CYP2A6 enzyme, play a crucial role in smoking behavior and addiction. Fast metabolizers tend to smoke more frequently due to rapid nicotine clearance, while slow metabolizers experience prolonged nicotine effects, making them less likely to develop severe addiction. These genetic differences influence smoking cessation success, with fast metabolizers requiring higher doses of nicotine replacement therapy or alternative medications. Recognizing the role of genetics in nicotine addiction can lead to personalized treatment strategies, improving quit rates and reducing smoking-related health risks.

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