The impact of tobacco smoking on human health is a favorite topic for journalists. There are thousands of brochures, articles and books about how smoking is harmful and how to get rid of nicotine addiction. As a rule, the authors limit themselves to a consideration of the psychological aspect or focus the reader's attention solely on the grave medical consequences of smoking. And as a rule, no one describes the mechanism of nicotine addiction or the interaction of tobacco with the body at the molecular level. I will try to address this shortcoming in the literature on smoking.
A little about the history of tobacco
Everyone knows that the use of tobacco was taught to Europeans by the American Indians. Shortly after Columbus' expeditions at the end of the 15th century, the Spaniards began to cultivate tobacco. Tobacco owes its scientific name (lat. Nicotiana) to the French ambassador to Portugal, Jacques Nico, the famous tobacco popularizer of the second half of the 16th century. Niko's authority was so great that tobacco quickly became used not only for entertainment purposes, but also in medical practice. Thus, in 1571, the Spanish physician Nicolas Monardez wrote a book on medicinal plants in which he claimed that tobacco cured 36 diseases.
Everyone knows that the use of tobacco was taught to Europeans by the American Indians. Shortly after Columbus' expeditions at the end of the 15th century, the Spaniards began to cultivate tobacco. Tobacco owes its scientific name (lat. Nicotiana) to the French ambassador to Portugal, Jacques Nico, the famous tobacco popularizer of the second half of the 16th century. Niko's authority was so great that tobacco quickly became used not only for entertainment purposes, but also in medical practice. Thus, in 1571, the Spanish physician Nicolas Monardez wrote a book on medicinal plants in which he claimed that tobacco cured 36 diseases.
The fight against tobacco use began in the 17th century. King James I of England was one of the first to implement anti-tobacco policy. In a treatise "A counterblaste to tobacco" in 1604 he called tobacco "a custom disgusting to the sight, disgusting to the smell, harmful to the brain and dangerous to the lungs". The treatise was followed by a 40-fold increase in tobacco duty. In the Ottoman Empire, smoking was forbidden in 1633 by decree of Sultan Murad IV and was punishable by death, but the prohibition was soon replaced by a tax. In many other European and Asian countries there were for quite a long time obstacles to the spread of tobacco, as well as various penalties up to execution.
In 1828, scientists from Heidelberg isolated nicotine in its pure form and concluded that it was a strong poison. Shortly thereafter, nicotine was used as an insecticide. Cigarettes appeared around the same time, but were still less popular than cigars. Despite the global spread of tobacco, tobacco smoking is not yet recognized as a worldwide problem. So, by 1889 only 140 cases of lung cancer were documented worldwide. In the same year, English physiologist John Newport Langley described the effect of nicotine on nerve ganglion conduction: nicotine blocked impulse transmission in the sympathetic nervous system.
At the beginning of the 20th century, cigarettes became a major tobacco product, and the world's largest tobacco companies were based in the United States. In 1912, oncologist Isaac Adler first pointed out the link between smoking and lung cancer. Lung cancer remained a rare disease until World War I, after which smoking became a widespread habit due to the inclusion of cigarettes in army rations.
In the 1930s, the link between smoking and lung cancer as well as reduced life expectancy was rigorously proven. Yet tobacco continued to grow in popularity at an unprecedented rate. It was not until the 1980s that nicotine addiction was globally recognized, followed by restrictions on advertising and distribution of tobacco products. It was in the 1980s that health authorities around the world began to fight tobacco use, despite which the tobacco industry is still thriving and growing every year.
In the 1930s, the link between smoking and lung cancer as well as reduced life expectancy was rigorously proven. Yet tobacco continued to grow in popularity at an unprecedented rate. It was not until the 1980s that nicotine addiction was globally recognized, followed by restrictions on advertising and distribution of tobacco products. It was in the 1980s that health authorities around the world began to fight tobacco use, despite which the tobacco industry is still thriving and growing every year.
How does nicotine addiction occur?
Tobacco would certainly not have become so popular if it did not cause addiction. However, the mechanism of nicotine's effect on the nervous system became known relatively recently. To understand this mechanism, we first need to know how nerve impulses are transmitted.
As a result of energy-dependent withdrawal of three Na+ ions from the cell in exchange for input of two K+ ions, neurons create an electrochemical gradient on their membrane - the cell is polarized (negative charge is accumulated inside, and positive charge - outside). When the cell is stimulated, depolarization occurs: channels open in the cell membrane, equalizing the Na+ concentrations on both sides of it.
Opening of channels in one place triggers chain depolarization in the whole cell. If the sodium channels remained open, the neuron would be permanently depolarized. However, this is not the case, because the sodium channels open only for a few milliseconds, and they are followed by opening of other channels, removing K+ from the cells, which promotes repolarization. The wave-like opening of sodium and potassium channels is called the action potential (AP).
Tobacco would certainly not have become so popular if it did not cause addiction. However, the mechanism of nicotine's effect on the nervous system became known relatively recently. To understand this mechanism, we first need to know how nerve impulses are transmitted.
As a result of energy-dependent withdrawal of three Na+ ions from the cell in exchange for input of two K+ ions, neurons create an electrochemical gradient on their membrane - the cell is polarized (negative charge is accumulated inside, and positive charge - outside). When the cell is stimulated, depolarization occurs: channels open in the cell membrane, equalizing the Na+ concentrations on both sides of it.
Opening of channels in one place triggers chain depolarization in the whole cell. If the sodium channels remained open, the neuron would be permanently depolarized. However, this is not the case, because the sodium channels open only for a few milliseconds, and they are followed by opening of other channels, removing K+ from the cells, which promotes repolarization. The wave-like opening of sodium and potassium channels is called the action potential (AP).
Action potential transfer from one neuron to another is different from intracellular transfer. When the action potential reaches the contact of two neurons, the excited cell receives not Na+ but many Ca2+ ions, which signal the release of neurotransmitters into the intercellular gap. Neurotransmitters, binding with ion channels (receptors) on the membrane of the receiving cell, trigger an action potential in it.
Nicotine is structurally similar to and mimics one of the most common neurotransmitters in the body-acetylcholine (ACh)-which is why some cellular ACh receptors became known as nicotinic receptors.
When the body relies on externally supplied nicotine instead of ACh, addiction occurs. More specifically, nicotine addiction is caused by the substitution of ACh in the tegmentum, also known as the pleasure center. When there is a natural concentration of Atsch, the arousal and suppression of the pleasure center are balanced.
But with regular nicotine use, neurons adapt: there are fewer nicotinic receptors in synapses, which lead to suppression of the tegmentum (α4β2), when the number of receptors leading to its activation (α7) remains the same. It is also worth considering that nicotine is very stable and therefore leads to a much more prolonged stimulation of the pleasure center than ACh, which degrades in synapses in a matter of milliseconds.
When the body relies on externally supplied nicotine instead of ACh, addiction occurs. More specifically, nicotine addiction is caused by the substitution of ACh in the tegmentum, also known as the pleasure center. When there is a natural concentration of Atsch, the arousal and suppression of the pleasure center are balanced.
But with regular nicotine use, neurons adapt: there are fewer nicotinic receptors in synapses, which lead to suppression of the tegmentum (α4β2), when the number of receptors leading to its activation (α7) remains the same. It is also worth considering that nicotine is very stable and therefore leads to a much more prolonged stimulation of the pleasure center than ACh, which degrades in synapses in a matter of milliseconds.
Stimulation of the tegmentum is a key moment in the formation of addictions of various kinds and behavior in general. But the pleasurable sensations caused by nicotine are only one side of the coin. We shouldn't forget the withdrawal syndrome, which causes most smokers who decide to quit to relapse again and again.
Withdrawal syndrome consists of loss of concentration, anxiety, depression, insomnia, and increased appetite when quitting nicotine use. You often hear that cigarettes help with stress, but stress and withdrawal syndrome are very similar in terms of physiology, which makes you question the sedative properties of nicotine. To date, it is not known exactly how nicotine withdrawal leads to withdrawal syndrome. Nevertheless, it is clear that an important role in its emergence is played by the center of discontent - habenula - which suppresses tegmentum when we don't get what we want. This part of the brain is also highly dependent on nicotine receptors, and it is likely that neuroadaptation occurs there as well, leading to unpleasant feelings when nicotine is scarce.
Withdrawal syndrome consists of loss of concentration, anxiety, depression, insomnia, and increased appetite when quitting nicotine use. You often hear that cigarettes help with stress, but stress and withdrawal syndrome are very similar in terms of physiology, which makes you question the sedative properties of nicotine. To date, it is not known exactly how nicotine withdrawal leads to withdrawal syndrome. Nevertheless, it is clear that an important role in its emergence is played by the center of discontent - habenula - which suppresses tegmentum when we don't get what we want. This part of the brain is also highly dependent on nicotine receptors, and it is likely that neuroadaptation occurs there as well, leading to unpleasant feelings when nicotine is scarce.
Physiological effects of nicotine
Nicotine can be consumed in many ways, but smoking cigarettes is the most common. While smoking, most of the nicotine is burned in the flame, but the small amount of nicotine inhaled is compensated for by the giant surface area of the lungs, through which it is absorbed into the bloodstream. When chewing tobacco, nicotine concentrations in saliva are up to 6 orders of magnitude higher than concentrations in lung fluids after a single cigarette.
Nicotine entering the body in one way or another stimulates nicotine receptors not only in the brain but also in all other tissues. In the lungs, nicotine stimulates mucosal cell division by activating the corresponding receptor. Excessive cell division, combined with DNA damage caused by tobacco carcinogens, can lead to lung carcinoma. Similar phenomena have been observed in cells throughout the body, causing nicotine consumption (not even through smoking) to increase the risk of breast, uterine and digestive tract cancers.
Nicotine can be consumed in many ways, but smoking cigarettes is the most common. While smoking, most of the nicotine is burned in the flame, but the small amount of nicotine inhaled is compensated for by the giant surface area of the lungs, through which it is absorbed into the bloodstream. When chewing tobacco, nicotine concentrations in saliva are up to 6 orders of magnitude higher than concentrations in lung fluids after a single cigarette.
Nicotine entering the body in one way or another stimulates nicotine receptors not only in the brain but also in all other tissues. In the lungs, nicotine stimulates mucosal cell division by activating the corresponding receptor. Excessive cell division, combined with DNA damage caused by tobacco carcinogens, can lead to lung carcinoma. Similar phenomena have been observed in cells throughout the body, causing nicotine consumption (not even through smoking) to increase the risk of breast, uterine and digestive tract cancers.
The effects of tobacco smoke and nicotine on the immune system are extremely interesting. Depending on frequency, smoking history, and individual differences, tobacco smoke can both stimulate and suppress the immune system. For example, tobacco smoke is rich in reactive oxygen species that cause chronic lung inflammation, meaning it generally stimulates the immune system. Although some studies have shown that tobacco smoke activates immune T cells, this does not mean that tobacco is good for immunity: medical statistics show that smokers suffer more often and more seriously from colds, pneumonia and tuberculosis than nonsmokers. In addition, other studies, which focus more on antiviral immunity, have shown that tobacco smoke reduces the body's resistance to viruses.
Smoking also affects the course of autoimmune diseases. Smoking is known to aggravate rheumatoid arthritis, Crohn's disease and contribute to pulmonary emphysema. More recently, people have begun to understand the reasons for this: activated T cells begin to produce antibodies to elastin, a structural protein of the lungs, arteries and skin. Such antibodies target the smoker's own immune system. The autoimmune aspect is one example of the irreversible health effects of tobacco smoke, because once created, the antibodies will continue to be synthesized even years after quitting smoking.
Smoking also affects the course of autoimmune diseases. Smoking is known to aggravate rheumatoid arthritis, Crohn's disease and contribute to pulmonary emphysema. More recently, people have begun to understand the reasons for this: activated T cells begin to produce antibodies to elastin, a structural protein of the lungs, arteries and skin. Such antibodies target the smoker's own immune system. The autoimmune aspect is one example of the irreversible health effects of tobacco smoke, because once created, the antibodies will continue to be synthesized even years after quitting smoking.
One often hears that smoking leads to cardiovascular diseases. To a large extent, these diseases are provoked by the factors already mentioned: oxidative stress and inflammation.
Active oxygen forms contained in tobacco smoke reduce the activity of the enzyme responsible for relaxing blood vessels and lowering blood pressure - NO synthase. This enzyme produces nitric oxide NO, which reacts with reactive oxygen species to form the toxic molecule peroxynitrite. Thus, by reducing NO levels, smoking leads to hypertension, the main cause of coronary diseases. Smoking causes impotence by the same mechanism: NO deficiency leads to vasoconstriction and reduction of blood flow in all organs.
Active oxygen forms contained in tobacco smoke reduce the activity of the enzyme responsible for relaxing blood vessels and lowering blood pressure - NO synthase. This enzyme produces nitric oxide NO, which reacts with reactive oxygen species to form the toxic molecule peroxynitrite. Thus, by reducing NO levels, smoking leads to hypertension, the main cause of coronary diseases. Smoking causes impotence by the same mechanism: NO deficiency leads to vasoconstriction and reduction of blood flow in all organs.
Another problem that only male smokers can face is the loss of the male Y chromosome. Swedish scientists have found that the blood of smokers contains 3-4 more cells that have lost this strictly male part of the genome. This phenomenon may be related to the general genetic instability caused by the mutagens of tobacco smoke, and very likely contributes to the development of cancer.
Chronic lung inflammation in smokers activates white blood cells throughout the body, including the blood. Against the background of this inflammation, there is a decrease in the number of endothelial progenitor cells, which provide repair of damaged blood vessels and increase blood clotting.
How do you beat nicotine addiction?
In developed countries, half of all smokers try to quit every year, but only 2% succeed. This low success rate is due to the fact that smokers usually decide to quit suddenly and try to do so without resorting to aids.
The most popular way to treat nicotine addiction is nicotine replacement therapy. It is based on the idea that taking nicotine in controlled, steadily decreasing doses will eventually lead to recovery from addiction. The first drug for such therapy was nicotine chewing gum produced in 1971 by the Swedish company Nicorette.
Today, pharmacies sell dozens of products from different firms, based on the same mechanism of action: nicotine patches, inhalers, lozenges, sprays and, of course, gum. A number of studies have shown that nicotine replacement therapy is twice as effective as a placebo and would help three percent more smokers quit.
Chronic lung inflammation in smokers activates white blood cells throughout the body, including the blood. Against the background of this inflammation, there is a decrease in the number of endothelial progenitor cells, which provide repair of damaged blood vessels and increase blood clotting.
How do you beat nicotine addiction?
In developed countries, half of all smokers try to quit every year, but only 2% succeed. This low success rate is due to the fact that smokers usually decide to quit suddenly and try to do so without resorting to aids.
The most popular way to treat nicotine addiction is nicotine replacement therapy. It is based on the idea that taking nicotine in controlled, steadily decreasing doses will eventually lead to recovery from addiction. The first drug for such therapy was nicotine chewing gum produced in 1971 by the Swedish company Nicorette.
Today, pharmacies sell dozens of products from different firms, based on the same mechanism of action: nicotine patches, inhalers, lozenges, sprays and, of course, gum. A number of studies have shown that nicotine replacement therapy is twice as effective as a placebo and would help three percent more smokers quit.
Much less known are other, sometimes much more effective, smoking cures.
One such medicine is citicin, an alkaloid of the plant. This plant has been known to traditional medicine for centuries, and during World War II people began to consider it as a substitute for tobacco. Citizine appeared on the market even earlier than nicotine gum - in 1964, it began to be produced in Bulgaria under the brand name Tabex.
Citizine, like nicotine, can bind to nicotine receptors in the brain. But, firstly, it binds to them more strongly, that is, it keeps nicotine out, and secondly, it activates them more weakly. Thus, citizine prevents the reinforcement of addiction, even if the person continues to consume nicotine. If the person has stopped smoking and is experiencing discomfort, then citicin stimulates the pleasure center enough to eliminate the withdrawal syndrome, but not enough to form a new addiction.
One such medicine is citicin, an alkaloid of the plant. This plant has been known to traditional medicine for centuries, and during World War II people began to consider it as a substitute for tobacco. Citizine appeared on the market even earlier than nicotine gum - in 1964, it began to be produced in Bulgaria under the brand name Tabex.
Citizine, like nicotine, can bind to nicotine receptors in the brain. But, firstly, it binds to them more strongly, that is, it keeps nicotine out, and secondly, it activates them more weakly. Thus, citizine prevents the reinforcement of addiction, even if the person continues to consume nicotine. If the person has stopped smoking and is experiencing discomfort, then citicin stimulates the pleasure center enough to eliminate the withdrawal syndrome, but not enough to form a new addiction.
This drug is not widely used outside of Central and Eastern Europe. According to data from 2011, citizine is 3.5 times more effective than nicotine replacement therapy. However, it should be taken into account that, in general, less research has been conducted on citizine than on other drugs, which actually prevents its distribution in the world.
Varenicline, a drug from Pfizer, a major pharmaceutical corporation, has a similar mechanism of action and has been available since 2006. Varenicline has passed rigorous clinical trials and is sold worldwide. Its efficacy in long-term therapy is slightly higher than that of analogues, while the drug itself costs considerably more than nicotine gum and citizine.
Varenicline, a drug from Pfizer, a major pharmaceutical corporation, has a similar mechanism of action and has been available since 2006. Varenicline has passed rigorous clinical trials and is sold worldwide. Its efficacy in long-term therapy is slightly higher than that of analogues, while the drug itself costs considerably more than nicotine gum and citizine.
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Another common remedy for nicotine addiction is bupropion. This drug has been available since 1989 and is primarily positioned as an antidepressant. Its ability to make it easier to quit smoking is only a side effect: bupropion binds nicotine receptors in the brain but does not activate them. This substance is comparable in effectiveness to nicotine replacement therapy.
Conclusion
The action of all the described drugs is based on the binding of nicotine receptors in the brain. In recent years, a fundamentally different approach to the treatment of nicotine addiction has been actively developed - nicotine vaccination.
Vaccines of this kind can help not only from nicotine addiction, but also from any other chemical addiction (except alcohol). Usually the body does not produce antibodies against small molecules of psychoactive substances, so in vaccines these molecules are combined with larger proteins, which cause an immune response.
There have already been successful trials of nicotine, methamphetamine, cocaine, and opiate vaccines. With vaccination, the side effects of the treatment are much weaker and the effect is more stable than with drug therapy. But there are disadvantages: the vaccine has no effect at all on a quarter of addicts. In addition, anti-nicotine vaccination can be discouraged by its duration: the course consists of 4-5 injections over three months.
The genetic approach to nicotine addiction research has recently become very popular. Massive genome studies of smokers have already identified thousands of mutations that affect the likelihood of starting or quitting smoking and determine the severity of nicotine addiction. The findings can help create new cessation products or help choose the most effective ones already available.
The genetic approach to nicotine addiction research has recently become very popular. Massive genome studies of smokers have already identified thousands of mutations that affect the likelihood of starting or quitting smoking and determine the severity of nicotine addiction. The findings can help create new cessation products or help choose the most effective ones already available.
