SCIENCE CHINA Life Sciences • IN-SIGHT •

May 2010 Vol.53 No.5: 631–632 doi: 10.1007/s11427-010-0107-3

A revolutionary approach for the cessation of smoking LIU JianKang1,2* 1

Institute of Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Xi’an Jiaotong University School of Life Science and Technology, Xi’an 710049, China; 2 Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536, USA Received March 5, 2010; accepted March 31, 2010

Citation:

Liu J K. A revolutionary approach for the cessation of smoking. Sci China Life Sci, 2010, 53: 631–632, doi: 10.1007/s11427-010-0107-3

It is well known that smoking is harmful to our health. It is estimated that 1.3 billion people are smokers worldwide and 5.4 million deaths are caused by tobacco smoking each year. In China, about 1.2 million people die because of smoking each year, which is 2000 people per day. As is already known, smoking has been associated with many diseases, including cardiovascular disease, osteoporosis, loss of fertility, macular degeneration, neurodegeneration and a number of cancers, especially lung cancer. Chronic smoking reduces the human life span by an average of 7 years and disease-free life by up to 14 years [1]. Therefore, tobacco smoking is the second major cause of death and the fourth most common risk factor for disease worldwide. About 85% of smokers are nicotine addicted [2]. Nicotine addiction is the main impediment preventing cessation of cigarette smoking. Therefore, cigarette smoking has been classified as a chronic disease with frequent relapsing. It is known that genetic and environmental factors both contribute to smoking initiation and smoking persistence [3]. Smoking cessation has numerous immediate and major health benefits, including a very significant reduction in mortality. Nonpharmacological approaches to smoking cessation include educational, motivational and behavioral interventions, but they are generally ineffective for individual smokers [3]. By contrast, pharmacotherapies approved for smoking cessation have proven to be more effective. The most common approaches include nicotine replacement therapy, bupropion, varenicline and other antidepressants, clonidine, an α2-adrenergic and imidazoline agonist, or combination therapy of bupropion and nicotine [3]. However, all these therapies have limited effectiveness. For example, the quit rate for nicotine replacement therapy is 17% (range 12%–34%) at 6–12 months when administered with limited behavioral therapy [4]. The side effects are of serious concern with these approaches. For example, various nicotine replacement therapies can cause orogastric irritation and diarrhea (nicotine gum), nasal irritation and bronchospasm in asthmatics (nicotine nasal spray), oropharyngeal irritation and bronchospasm in asthmatics (nicotine inhaler), and insomnia and skin irritation (nicotine patch). Bupropion causes insomnia, lowered seizure threshold, and an increased suicide rate, and varenicline can induce insomnia, vivid dreams and nausea [3]. Therefore, researchers and smokers are both interested in finding more effective approaches with fewer side effects. Rimonabant, a cannabinoid receptor antagonist, initially marketed as an antiobesity drug, has been shown to increase abstinence at 1 year by 60% vs. placebo [5]. Another approach is administration of nicotine vaccines, which stimulate the production of antibodies against nicotine and have demonstrated efficacy in phase 2 trials [6]. Compared with all of the above approaches, Zhao and his collaborators have found a simpler but more effective way to achieve smoking cessation without any side effects [7]. They developed a cigarette filter incorporating green tea components (with L-theanine as the major active component). In one clinical trial, they showed that after 2 months, use of this filter reduced the number of cigarettes smoked per day by 52%. Thirty-one percent of smokers were able to completely quit smoking.

*Corresponding author (email: [email protected]) © Science China Press and Springer-Verlag Berlin Heidelberg 2010

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May (2010) Vol.53 No.5

In another clinical trial, 3-months use of the cigarette filter reduced cigarette consumption by 48% in the first month, by 83% in the second month, and by 91% in the third month. The average number of cigarettes smoked declined from 24.5 to 3 per day in the third month. These results are extraordinary because they are better than any other approach available, either pharmacologic or non-pharmacologic. Therefore, we think it is a revolutionary approach to smoking cessation. Green tea drinking has long been known to have beneficial effects on human health. L-Theanine is an amino acid found uniquely in green tea. L-Theanine has been reported to be a relaxing agent, improving learning and memory; behavioral studies in animal models demonstrate it exerts neuroprotective effects, possibly through its antagonistic effects on group 1 metabotropic glutamate receptors [8]. L-Theanine is also capable of counteracting excitotoxicity and/or mitochondrial radical formation [9]. As a major component of green tea, L-theanine may interact with caffeine, another important component of green tea, to enhance performance in terms of attention switching and the ability to ignore distraction; this is likely to be reflective of higher-level cognitive activity and may be sensitive to the detrimental effects of overstimulation [10]. Neurochemical studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, kainate and NMDA receptors. Zhao and his collaborators did a mechanistic study in animals and found that L-theanine in a cigarette filter could significantly inhibit both the preference for nicotine in mice and the release of dopamine; similar effects are produced by inhibitors of nicotine acetylcholine receptors (nAChRs). It is the interaction of nACHRs and nicotine that causes nicotine addiction [11]. They also demonstrated that their cigarette filter significantly reduced the toxicants in smoking and the smoking-induced acute and chronic toxicity. The question arises as to whether enough of the major active components in the filter can enter the human body to become effective. Zhao and his collaborators have used special equipment to collect the gases emitted by the cigarette and tested them by HPLC. They found that one cigarette with the filter attached released 65 μg of L-theanine. In addition, they also showed that the L-theanine blood levels could be as high as 10 μg mL−1 when plasma was exposed to the smoke of 7 cigarettes. These results clearly suggest that the heat of the burning cigarette can drive enough L-theanine out of the filter by distillation so that an effective amount can enter the respiratory tract and blood circulation. Because the active components of the green tea extract mainly work on the brain, a second concern is whether the active component can penetrate the blood brain barrier. It has been shown that once L-theanine has entered the blood circulation, it can easily pass through the blood brain barrier and arrive at the target areas in the central nervous system [10]. An important problem with smoking cessation approaches is the high relapse rate following cessation therapy. For example, whether or not nicotine replacement therapy was used in the initial quitting attempt, one in three quitters relapses within 4 years [12]. Whether this green tea cigarette filter can overcome the relapse problem is not yet known; however, there is a great possibility that this approach may lower the relapse rate or increase the number of smokers who quit permanently, due to its unique mechanism. In summary, Zhao and his collaborators have developed a simple but revolutionary approach for smoking cessation. The wide application of this approach will benefit and have great impact on human health, the economy (especially the tobacco industry) and the environment. It is known that green tea extract contains more than 450 kinds of compounds. Therefore, in addition to L-theanine, there must be other important components that have an effect on nicotine addiction, either alone or synergistically with L-theanine. These should be studied further.

The author thanks Dr. Edward Sharman at the University of California, Irvine for his critical reading and comments. This work was supported by Xi’an Jiaotong University plans 211 and 985.

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