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Few people talk about the benefits of nicotine. But on the topic that nicotine is harmful to the human body, we can talk for a long time, based on scientific facts, which scientists and others cite in their works. Cigarette packages also contain pictures that warn people about the health hazards of smoking.

Of course, there is some truth in this, people die from nicotine if they use it in excessive quantities, but we would like to talk about how nicotine is useful.

Is there any benefit to nicotine?

First, let's figure out why so much attention has been paid to the topic of the harmfulness of nicotine. Doctors have been studying this issue for many years and have brought great amount There is no evidence that nicotine is beneficial. But when a person smokes a cigarette, he simultaneously absorbs a lot of carcinogenic smoke, and nicotine has absolutely nothing to do with it.

On the contrary, if cigarettes contain very little nicotine, in this case they are harmful to human health, especially if the smoker is accustomed to inhaling deeply. Scientists have known about this for a long time, it’s just that now it’s not customary to talk about the beneficial properties of nicotine. What other arguments have been given about the benefits of nicotine for the human body?

Nicotine negatively affects people's taste and olfactory receptors. That is why those who smoke taste food completely differently; it seems bland to them. Thanks to this, appetite decreases, and, as a result, it goes away. excess weight. For people suffering from obesity, this fact is just a godsend. The only thing is that appetite increases very strongly when a person tries to quit smoking. Then the kilograms return at a rapid pace.

1. Nicotine and Alzheimer's disease

In 1992, Dr. James Da'Fan made a great discovery about the benefits of nicotine. He convinced the whole world that smoking is great preventive method in the fight against Alzheimer's disease. According to the scientist, those who smoke almost never suffer from dementia in old age.

By the way, it should be noted that the scientist’s conclusion is not refuted by American doctors. They found that nicotine, when it enters the human body, begins to actively disintegrate in it, turning into “nornicotine” - a substance thanks to which brain neurons do not die. But it should also be noted here that the resulting substance is toxic, so you should not abuse cigarettes just to save yourself from the fate of facing Alzheimer's disease in old age.

2. Nicotine against Parkinson's disease

American scientists have discovered another fact about how nicotine is beneficial for humans. A doctor named Harvey Checkoway from Washington has proven that people who smoke are 70% less likely to develop a disease such as Parkinson's disease, which progresses very slowly and develops into chronic pathology related to neurology.

As a rule, this diagnosis is made to elderly people. What is the benefit of nicotine in this case? The substance has a very beneficial effect on the genes of dopamine receptors, thanks to which old people can boast of good attention, they are always concentrated, but not for a long time. To maintain concentration, you need to constantly smoke a cigarette. But again, we must not forget about the toxicity of nicotine, which can simply destroy human health.

It turns out that nicotine alleviates the symptoms of schizophrenia because this substance has a good effect on a person’s thought process and inhibits the progression of the disease. If you read the composition of numerous drugs that are prescribed to schizophrenics, you can be convinced that nicotine is also included in it, because it is thanks to it that it is possible to stop the patient’s hallucinations, his apathy and indifference in everything.

3. The beneficial effects of nicotine on the digestive system

Doctors in the field of gastroenterology have discovered another fact about how nicotine is beneficial. According to them, this substance reduces peristalsis in the intestines. After a person smokes several cigarettes, gas formation in the organs digestive tract noticeably decreases, because mucus in some parts of the intestine, under the influence of nicotine, begins to be intensively produced, and due to this, the likelihood of the formation of ulcerative colitis in humans is reduced. Moreover, those who smoke never experience diarrhea.

But in addition to the unambiguous benefits of nicotine, it is necessary to mention its harm - it is it that provokes the active development of cancer. According to WHO, smokers are the most likely to become victims of cancer.

4. The benefits of nicotine for women's health

American scientists believe that the female hormone estrogen depends on the level of nicotine that enters the woman’s body. According to doctors from Dortmund, if a woman smokes, then she has:

• the risk of developing malignant tumors on the endometrium of the uterus is automatically reduced (due to the influence of nicotine, cells do not divide so quickly, especially cancerous ones);
• fibromatous nodes do not form on the uterus - that is, connective tissue does not grow because this process in the body is inhibited;
• Endometriosis never occurs in girls who started smoking in early age(this fact has not yet been scientifically proven, scientists are working in this direction to find a relationship);
• in pregnant women who smoke, nicotine prevents eclampsia - it does not increase arterial pressure, and preeclampsia - they do not develop gestosis, which can impair cerebral circulation in mother and child. All these are only indirect advantages, which it is better for pregnant women to forget about if it is important to preserve the health of their baby and protect him from the possibility of being born with numerous defects of internal organs.

To this day, it has not been possible to determine exactly why such significant things happen in the body of a woman who smokes. There is an assumption that when tobacco gets into the lungs, it disintegrates and a potassium salt (thiocyanate) is formed, which has a very high hypotensive property, that is, the ability to lower blood pressure.

In addition, scientists from the USA have established many more facts about how nicotine is beneficial for women’s health.

These include the following items:

• Nicotine relieves dysmenorrhea, meaning a woman can survive menstrual period without pain and other unpleasant symptoms that give her severe discomfort. This is achieved due to the effect of tobacco on prostaglandins, which are the sources of dysmenorrhea. However, if you are looking for a way to get rid of unpleasant symptoms during menstruation, then it is better to simply take some kind of painkiller than poison your body with tobacco smoke.
• It does not form in the mammary glands and on the cervix malignant neoplasms during the period when a woman reaches menopause, because nicotine inhibits uncontrolled cell division.

In addition to the benefits of nicotine, it is also necessary to mention its harm to the health of a woman, especially one who is carrying a child under her heart. If a pregnant woman smokes excessively, then she is highly likely to go into premature labor. In addition, a smoking mother runs the risk of giving birth to a sick baby.

5. The benefits of nicotine in stressful situations

Continuing to argue for the benefits of nicotine, doctors say that this substance helps a person cope with stressful situations in life. Every smoker knows that after smoking one or two cigarettes, the whole world seems kinder, nicer and happier. Why does this happen? This fact can be explained by certain physiological processes occurring in the human body after receiving a dose of nicotine:

• breathing at the moment of smoking becomes rhythmic and balanced (all this helps the person to calm down);
• the smoke emanating from a cigarette relaxes the mind (especially if the smoker, while smoking, is accustomed to observing the smoke rings that form when he exhales);
• at the moment of inhaling a cigarette, provided there is complete silence around, a person completely relaxes;
• nicotine activates mediators responsible for the production of the “hormone of happiness” (which is why all smokers, in the event of any problem or unpleasant situation, experience a craving for smoking and immediately run around the corner to smoke a few cigarettes).

Note that the noticeable improvement in the smoker’s mood at the moment of inhaling is short-lived. After some time, apathy returns again, a desire arises to smoke a cigarette again in order to fall into a state of euphoria, which a person likes so much and helps him cope with numerous difficulties in life.

6. Nicotine will prevent allergies

Famous scientists of mankind provide several scientifically proven arguments regarding why nicotine is also useful. In their opinion, this substance reduces the likelihood of a person developing allergies, because at the moment of smoking even one cigarette, mastocytes (cells that play a vital role in the body’s adaptation to the effects of a number of allergens) begin to actively grow.

For example, allergic ailments such as urticaria or hay fever are much easier for a smoker. Of course, a person who is prone to allergies cannot afford to escape from it by stocking up on thousands of cartons of cigarettes. This is too reckless and unreasonable action. In addition, do not forget that tobacco smoke itself can be an allergen. It is he who provokes the development of complicated diseases of the bronchopulmonary system in humans, for example, asthma.

Nicotine: more benefit or harm?

Based on all that has been said about the benefits of nicotine, it must be said that everything is completely ambiguous on this issue. You can’t afford to believe only those doctors who are convinced that smoking can only cause harm to human health, but you shouldn’t follow the lead of scientists who give dubious arguments about why nicotine is beneficial. Just stop believing in stereotypes and understand that nicotine can be a dangerous substance for humans, because it enters the body along with carcinogenic tobacco smoke, but in some cases it can also be beneficial, but short-term.

Still, a person who smokes absorbs not only nicotine and carcinogenic smoke, but also numerous dangerous substances that are part of it, and there are more than 400 of them. Naturally, they cause numerous factors in the human body that lead to the development of life-threatening ailments , some of them become simply incompatible with life.

Nevertheless, knowing all this, many doctors are smokers, and heavy smokers. How can this fact be explained? We won't talk about how stressful the job is here. medical personnel. It’s just not a problem for doctors to find a “golden mean” in smoking, so that their bodies receive benefits from nicotine, and not just harm. They believe that if you smoke within “reasonable limits,” you don’t have to worry about ruining your health.

What does it mean, within “reasonable limits”:

• You cannot smoke more than 4 cigarettes per day (this applies to men of large build);
• Sick people and women, especially pregnant women, should not smoke more than 2 cigarettes per week.

We still want to urge you to the fact that smoking is a vice that needs to be gotten rid of urgently. Still, it does more harm than good. Your health will definitely suffer if you smoke constantly. It cannot be considered a miracle cure or psychotropic drug. If you want to live a long time, not get sick, and not constantly visit hospitals and other medical institutions, then you should definitely give up the habit of smoking. This way you will not only save your life and protect your loved ones from carcinogenic smoke, which they will also have to breathe, but also significantly save money to spend on something more useful.

Since the end of the 17th century, humanity has known what nicotine is. It belongs to the alkaloids. It is found in abundance in plants from the nightshade family. The highest harmful concentrations of nicotine are observed in tobacco leaves and shag. The alkaloid is a toxic substance. It contains toxic psychotropic components and is similar in action to a drug. Due to widespread tobacco smoking, the mortality rate among the entire population of the planet has increased many times over.

The use of an alkaloid provokes pathologies of the cardiovascular system. This applies not only to smoking cigarettes and hookah, but also to the use of mixtures, weed, and chewing tobacco (nasvay). Nicotine is also present in electronic cigarettes.

Nicotine often leads to intoxication. The main danger of the substance lies in its ability to provoke cancer in humans. Due to the fact that smokers inhale and exhale smoke, the effects of factors that increase the risk of developing over 15 types of cancer are enhanced. It selects the lungs, stomach, and larynx as the main target organs and penetrates their tissues. The substance reduces the process of natural death of body cells, which leads to their degeneration into tumors.

Due to the effect of nicotine on the body, blood vessels grow in cancer cells. This phenomenon is confirmed by pathophysiology. This branch of medicine has established a pattern between smoking and the development of cancer in humans. The negative effects of nicotine on vision have been confirmed. It also slows down muscle growth and protein synthesis.

Alkaloid renders Negative influence on the health of pregnant women. He becomes the reason congenital pathologies in children. A child born to a smoking woman is more likely to develop type II diabetes. Children whose mothers smoked during pregnancy are more likely to develop respiratory disorders and neurobehavioral defects.

Proven fact negative impact alkaloid on the reproductive system. It worsens the quality of sperm in men, becoming a factor in the subsequent development of infertility.

The effect of nicotine on the human body causes paralysis of the nervous system. Doses of 0.5 to 1 mg/kg are sufficient to stop breathing, cardiac arrest and death. Frequent exposure of the alkaloid to the body means the formation of persistent not only physical but also mental dependence.

The substance affects the brain and central nervous system. The alkaloid stimulates the production of serotonin, endorphins, dopamine, norepinephrine and aminobutyric acid. These substances contribute to the formation of pleasure, peace and happiness in the smoker. This artificial stimulation underlies the development of depression, schizophrenia and other disorders in humans. In terms of the power of influence on the human psyche, nicotine is similar to alcohol.

Impact on the body

The alkaloid negatively affects all health indicators. It harms the heart and blood vessels, gastrointestinal tract, brain, respiratory organs, and reproductive system. Nicotine smoke has a negative effect on the condition of the skin and accelerates the aging process. Tobacco causes deep wrinkles to appear faster on the dermis of the face. The alkaloid also reduces immunity in humans.

Gastrointestinal tract

Tobacco smoke affects all elements, from teeth to intestines. Smokers experience the following phenomena in the gastrointestinal tract:

• increased salivation;
• constant irritation of the oral mucosa;
• frequent bleeding gums;
• yellowing of teeth, thinning of their enamel;
• development of periodontitis;
• decreased appetite (use of the alkaloid replaces food intake);
• excessive production of hydrochloric acid by the stomach;
• release of stomach contents into the esophagus, leading to contraction of its muscles and the formation of erosions and ulcers in it;
• slowing down the process of digesting food;
• deterioration of liver function;
• violation of normal weight;
• failure in the intestines in the form of loss of essential minerals and vitamins;
• the appearance of diarrhea and constipation.

Due to the intake of nicotine, stomach cramps occur. Against the background of oxygen starvation of the blood, the organ begins to contract, and severe irritation occurs in its mucous membranes. The consequence of smoking is the development of gastritis, which is one of the precursors of stomach cancer. Due to nicotine addiction, ulcers and gastroesophageal reflux often occur.

Cardiovascular apparatus

Tobacco alkaloids provoke an increase in blood viscosity. This creates a risk of blood clots. Nicotine also affects the blood supply to tissues. Its influence contributes to increased blood pressure. Smokers often develop arterial hypertension. Frequent signs of nicotine addiction are arrhythmia and rapid heartbeat.

A side effect of tobacco use is the active formation of cholesterol plaques on the walls of blood vessels. All this leads to an increased risk of developing myocardial infarction and stroke. Nicotine also causes coronary artery disease. With a long history of smoking, a person begins to progress to heart failure. The alkaloid leads to a lack of iron in the blood, which causes anemia.

State of the brain and central nervous system

There are several known options for how the neurotoxins present in nicotine affect the central nervous system. Small doses of the substance are its stimulants, leading to stimulation of receptors. But this effect of smoking is short-term. Prolonged supply of nicotine to the brain can give rise to the development of an acute lack of oxygen. Against the background of its deficiency, a person’s risk of sudden death from a stroke increases.

Smoking harms the activity of the central nervous system, which leads to the following changes and characteristic symptoms:

• constant irritability;
• lethargy;
• headaches turning into migraines;
• drowsiness.

Due to a disruption in cerebral circulation, smokers develop atherosclerosis.

Respiratory system

IN medical science the alkaloid is considered one of the most common mechanisms of occurrence lung cancer in smokers. A common consequence tobacco use leads to the development of malignant neoplasms in the oral cavity and larynx, requiring urgent surgery.

Important! In men who smoke, the incidence of respiratory cancer is 17.2% higher than in those who do not have this habit. Among women, the figure is 11.6%. Among non-smokers of both sexes, the incidence of lung cancer is 1.3%. Statistics reflect data for recent years.

The main harmfulness of nicotine manifests itself in provoking chronic bronchitis and asthma. The reason lies in the excessive production of sputum, which accumulates in the respiratory tract. They begin to clear themselves through coughing every time a person smokes.

People who abuse tobacco are more likely to experience respiratory infections in the form of laryngitis, sore throat and pharyngitis. For the majority of smokers, a typical case is emphysema. The most common consequence of long-term cigarette use is the development of chronic pulmonary obstruction.

Reproductive system

The use of smoking weed, tobacco mixtures, vaping, electronic cigarettes, and marijuana leads to a distortion of spermatogenesis in men. Against this background, the quality of seminal fluid deteriorates. This circumstance serves as an active factor in the development of impotence and infertility.

During pregnancy in women, nicotine leads to the following consequences:

• increased risk of sudden fetal death (especially at the embryonic stage);
• development of asphyxia in the womb;
• provoking premature birth during any period of pregnancy;
• probable retardation of adolescents in physical and intellectual development, frequent illnesses during growing up.

A nursing mother who continues to smoke transfers all the toxic components of tobacco to her newborn along with breast milk, which can cause severe poisoning in him. The alkaloid also disrupts hormonal background among representatives of the fairer sex, which is reflected in work failure thyroid gland. Because of it, estrogen compensation is reduced, which is the main factor in the development of female infertility. Nicotine also worsens heredity in subsequent generations.

The main harm of cigarettes on the human body is the formation of a drug addiction similar to it. At the same time, abstinence (independent refusal of the habit of one’s own free will) is significantly difficult due to the persistent mental and physical need for smoking. When treating addiction, it is necessary to prescribe special anti-nicotine medications and sedatives. However, they do not guarantee complete cessation of addiction. You can quit the habit by sewing a special capsule under the skin or fixing an anti-nicotine patch on it.

Cigarette smoke causes disruption in the functioning of absolutely all structures. The most vulnerable systems are the respiratory, cardiovascular, digestive and reproductive systems. The smoker's skin and hair suffer significantly from the effects of nicotine tar. A bad habit reduces immune defense; it provokes cancer more often than other addictions. Smoking is also one of the factors in the development of tetanus, for which it is necessary to be vaccinated.

Useful video

Nicotine addiction will be discussed below:

In contact with

Nicotine is the best known and one of many alkaloids found naturally in tobacco. Nicotine itself is present in many other nightshade plants, such as eggplants and peppers, but in minimal quantities. The effect of pure nicotine isolated from tobacco products or cigarettes is significantly different from the effect of tobacco itself, and in any case should be considered as the effect of a separate substance. Essentially, nicotine has multiple mechanisms of action. The first is that it mimics the action of the neurotransmitter acetylcholine and can directly activate acetylcholine receptors, which can then induce an increase in catecholamines such as adrenaline and dopamine. This mechanism underlies both the potential addiction to nicotine and the fat burning mechanism. Nicotine may also act as an anti-estrogen compound by directly inhibiting aromatase and one of the two estrogen receptors, which may underlie some of the side effects associated with chronic nicotine use, especially in women. Finally, nicotine by its nature causes oxidative stress, but at a level that is hormesis for the cell. This refers to the mimicking action of acetylcholine mentioned earlier and the anti-inflammatory effect. It is very likely that, due to its mechanisms of action on the body, nicotine is a fat burner, since as a result of its effects, the level of adrenaline increases, which then acts on beta-adrenergic receptors (the molecular target of ephedrine). Increased adrenaline levels mediate a significant but short-lived increase in metabolic rate in a moderate nicotine user. It is believed that increasing the rate of lipolysis (breakdown fatty acids) is not associated with adrenaline, but indirectly by other mechanisms, possibly causing oxidative stress. Increased levels of catecholamines also underlie many of the cognitive benefits of nicotine (mostly related to increased alertness and focus), while mimicking the effects of acetylcholine may contribute to the inherently nootropic effects. In relation to addiction, one can say that the risk of addiction is determined by the relationship between how much nicotine a person takes (the higher the amount, the greater the risk) and the speed at which nicotine reaches the brain (the faster the concentration of nicotine in the brain increases, the stronger the effects are felt and the higher risk of addiction). Dependence is not an inherent characteristic of nicotine, as evidenced by the results of nicotine therapy used to curb cigarette addiction. Gum and patches have less potential for addiction than cigarettes due to the speed at which nicotine reaches the brain. IN short term, due to increased catecholamine levels, the potential side effects of nicotine are similar to the acute side effects of other stimulants such as , or . In the long term, nicotine may rival ephedrine in its side effect profile, as they both suppress catecholamine secretion levels over time (yohimbe and caffeine lose their effectiveness within two weeks or less).

Nicotine: methods of use (recommended dosage, active quantities, other details)

Nicotine can be introduced into the body in several ways (excluding cigarettes, which are not recommended due to the risks that significantly outweigh the benefits of this method of taking nicotine):

An inhaler that allows you to quickly feel the effects of nicotine (and which inherently carries more risk than other methods due to the speed at which nicotine enters the body);

A nicotine patch that delays absorption for about an hour after application. The patch allows you to maintain a constant level of nicotine in the blood serum, but causes a smaller cognitive leap (minimal risk potential, minimal nootropic potential);

Chewing gum, the advantages and disadvantages of which are somewhere in between compared to the methods described above.

There is currently no evidence regarding the “optimal dose” of nicotine for a non-smoker. A non-smoker would be wise to follow the same directions as when taking stimulants, that is, start with small doses and increase gradually. This involves purchasing two milligram gummies or a quarter of a 24 milligram patch to start and then increasing to a level that seems minimal effective dose. At the moment there is no designated threshold level when the risk becomes too great, since this level is individual. When using nicotine in nicotine replacement therapy (to curb the craving for smoking), it is sufficient to follow the instructions for using the product. The amounts described in these instructions may be excessive for a non-smoker.

Sources and structure

Cigarettes and other sources

Nicotine is the main alkaloid in tobacco (minor alkaloids are nornicotine, anatabine, anabasine) and is present in tobacco leaves as a pesticide that kills insects that try to feed on them (the phytoalexins resveratrol and caffeine have a similar origin). Nicotine accounts for up to 1.5% of the total weight of commercial cigarette tobacco and 95% of its total alkaloid content. The average cigarette contains 10-14 mg of nicotine, but only 1-1.5 mg reaches the bloodstream after smoking. Most of the alkaloids found in tobacco are found only in tobacco and are structurally similar to nicotine, including myosmin, N"-methylmyosmin, cotinine, nicotirine, nornicotirine, nicotine N"-oxide, 2, 3"-bipyridyl, and metanicotine. Myosmin is not unique. alkaloid of tobacco and is quite widespread in the human diet, as is nicotine, which is present in small quantities in plants of the nightshade family (2-7 mcg/kg of vegetables).The average amount of nicotine that a person receives through vegetables from the nightshade family is at the level 1.4mcg per day, 95 percent of the population gets no more than 2.25mcg of nicotine from the vegetables they eat. This is about 444 times less than the amount of nicotine contained in one cigarette. Nicotine is the main alkaloid in tobacco. It is also present in plants of the nightshade family, such as eggplant, potatoes and tomatoes, but in such small quantities that it cannot cause the neurological effects that smoking does.

Pharmacology of nicotine

Absorption when smoking

Under normal conditions, nicotine is a weak base with a pKa = 8.0 and in acidic environments, where nicotine is usually in an ionized state, it cannot easily penetrate membranes. Smoke from warm air-dried cigarettes (pH 5.5-6.0) is in most cases acidic, so nicotine cannot easily pass through the oral mucosa. Some amount of nicotine can still pass through the mucous membrane, because Nicotine tar drops may have a higher pH level, but the majority of absorption in the case of tobacco smoking occurs in the respiratory tract. Nicotine can pass through the oral mucosa at elevated pH levels. This refers to air-cured tobacco, which is commonly used in pipes and cigars (different from the already mentioned warm air-cured tobacco of North American cigarettes). The nicotine in such tobacco is usually non-ionizing and can pass through the oral mucosa. In the mouth, nicotine can pass through the oral mucosa if the environment (tobacco smoke) is alkaline. This environment is typical for pipe tobacco, cigars and nicotine gum. In the lungs, nicotine is absorbed when it comes into contact with the alveoli. The rate of absorption is believed to be high due to the large area of ​​the alveoli and because the pH in the lungs is 7.4, which facilitates the transport of nicotine across the membrane. Nicotine is rapidly absorbed in the lung tissues.

Suction (other types)

Chewing tobacco, nicotine gum, and snuff have special pH-increasing substances added to help facilitate the passage of nicotine through the oral mucosa. The same substances are added to the nicotine patch to improve the absorption of nicotine by the skin. The overall bioavailability of nicotine in nicotine gum is less than with inhalation and is approximately 50-80%. Less bioavailability is due to the absorption of nicotine in the intestine, which enters there along with swallowed saliva under conditions of first-pass metabolism. Nicotine patches vary in absorption depending on the brand, although any patch usually delivers nicotine into the bloodstream within an hour of being applied. Residues of nicotine (10% of the patch content) still enter the bloodstream after the patch has been peeled off. This nicotine enters the bloodstream from the skin soaked in nicotine.

Pharmacokinetics in the bloodstream

Some studies of cigarette smoking show that Tmax (the time to reach the maximum concentration of nicotine in the blood) coincides with the end of smoking the cigarette, while for chewing tobacco and snuff the corresponding time is slightly longer (difficult to titrate), and chewing nicotine gum does not achieve this same maximum concentration nicotine in the blood, as with an equivalent dose of nicotine obtained from smoking cigarettes or using chewing tobacco. The first maximum effect of cigarette nicotine on the nervous system occurs within 10-20 seconds after a puff, however, the exact amount of nicotine a person receives during this time may vary, since the puffs themselves can be different (they can be large or small, their speed can be different , may be affected by how much air is diluted in the puff), although the average amount of nicotine reaching the systemic circulation for a typical smoker who prefers average North American cigarettes is 1-1.5 milligrams. Smoking cigarettes leads to a very rapid increase in the concentration of nicotine in the bloodstream. It is assumed that chewing gum, containing 6 milligrams of nicotine, increases the level of nicotine in the blood by 15-20 nanograms/milliliter, while smoking a cigarette can increase this level by 15-30 nanograms/milliliter.

Distribution

A pH level of 7.4 in the blood indicates that nicotine is in a state where the ratio of its ionized to non-ionized part is 69:31, and its binding to blood plasma proteins is less than 5%. The average steady-state volume of distribution of nicotine is 2.6 liters/kg. Nicotine is widely distributed throughout the body. Organs with the greatest affinity for nicotine are the liver, kidneys, spleen and lungs; the smallest is adipose tissue. This was determined through autopsies of smokers. The concentration of nicotine in skeletal muscles and in the blood is the same. In smokers, compared to non-smokers, nicotine may bind to brain tissue with greater affinity and have an increased ability to bind to the receptor. Nicotine accumulates in body fluids, especially saliva and gastric juice, due to ion scavenging, and can also accumulate in breast milk at a ratio of 2.9:1 (milk:plasma). In addition, it readily crosses the placental barrier and can accumulate in the amniotic fluid in concentrations slightly higher than serum concentrations and can penetrate the fetus.

Neurokinetics

Due to the rapid passage of smoke into the lungs, as well as rapid absorption into them, nicotine can be contained in the brain tissue 10-20 seconds after a cigarette puff, which is faster than with an intravenous injection. The rapid delivery of nicotine to the brain, as well as the addictive potential of nicotine (reward context), and, in addition, the ability of the smoker to control the smoking process in accordance with their own preferences, make cigarettes the most dangerous method nicotine use from the point of view of addiction. The volume of distribution of nicotine in plasma (100% is taken as the volume of distribution in non-brain plasma) is about 20% for the whole brain (negligible, as shown by the primate study in which this value was obtained) with a predominant distribution in the previsual field ( 29%) and amygdala (39%) and less widespread in the white matter (10%). However, the study that produced these findings used an aromatase inhibitor for the assessment, whereas in primates the distribution of aromatase rivals that reported above (although in humans large amounts of aromatase are found in the thalamus). Nicotine intake through cigarette smoking is, from a neurological point of view, the most effective method introduction of nicotine into the body due to its pharmacokinetics and the ability of the smoker to control the nicotine entering the body in accordance with individual needs.

Metabolism

Nicotine undergoes extensive metabolism through various pathways, but the main route of nicotine metabolism is through cotinine (70-80%). Despite the fact that 10-15% of all nicotine metabolic products excreted in urine is cotinine, the main metabolism occurs through cotinine, and cotinine itself undergoes further metabolization. The direct conversion of nicotine to cotinine occurs through the participation of an intermediary. This mediator is ionized nicotine-Δ1"(5")-iminium, the conversion of nicotine into which occurs thanks to the P450 enzyme CYP2A6. Further conversion to cotinine occurs due to cytoplasmic aldehyde oxidase. Cotinine can subsequently be glucuronidated and excreted in the urine as cotinine glucuronide, or can be transformed into cotinine-N-oxide or trans 3-hydroxycotinine (which can then also be glucuronidated and excreted in the urine). It should also be noted that nicotine itself can be glucuronidated and excreted in urine as nicotine glucuronide. This process occurs with 3-5% of the total amount of nicotine that enters the human body. It is believed that in addition to 10-15% of nicotine metabolized through cotinine and 3-5% of nicotine metabolized by glucuronidation, the remaining metabolic products are trans-3-hydroxycotinine (the most significant metabolite, 33-40% of metabolism), cotinine glucuronide (12-17 %) and trans 3-hydroxycotinine glucuronide (7-9%). The main route of nicotine metabolism is through cotinine. Cotinine is then either excreted unchanged in detectable amounts or it is further metabolized. Both nicotine or cotinine and cotinine metabolites can undergo glucuronidation (attachment of glucose to a molecule). Another phenomenon responsible for 4-7% of metabolism is nicotine N-oxide, which results from the reaction of nicotine with flavin monooxidase 3 (FMO3), and produces primarily the trans isomer nicotine N-oxide. It is a product of the urinary tract and can be found in urine or reduced back to nicotine in the intestines. This metabolite, together with the alkaline nicotine glucuronide (3-5% of all nicotine entering the body), is responsible for the bulk of what remains from metabolism through cotinine.

Enzyme interactions

It appears that the aromatase enzyme (CYP1A1/2) is inhibited by nicotine, with an IC50 value of 223+/-10µM, and since nicotine is twice as potent as its metabolite cotinine, the two together may inhibit aromatase more potently. High doses of androstenedione can reverse the aromatase inhibition of nicotine and cotinine. Other aromatase inhibitors found in tobacco include myosamine (IC50 33+/-2µM; 7 times more potent inhibitor than nicotine), anabasine, N-n-octanoylnornicotine (comparable to aminoglutethimide), and N-(4-hydroxyanedecanoyl)anabasine. Nicotine inhibits aromatase. However, it is a relatively weak inhibitor when considering the concentrations required to inhibit 50% of enzyme activity. Other substances found in tobacco are more potent aromatase inhibitors. In one study using intravenous injections of nicotine in baboons (at levels similar to the nicotine content of a cigarette; 0.015-0.3 mg/kg), inhibition of aromatase in the brain was observed.

Neurology

Neurophysiology

Injections of nicotine (in smokers) increase neural activity in the frontal and cingulate regions of the brain, as well as in the nucleus accumbens and amygdala, areas of the brain involved in processes associated with addiction.

Attention and reaction time

A meta-analysis of nicotine and its effects on the brain in humans showed that there is ample evidence that nicotine enhances attention (both the ability to respond instantly and to various external stimuli). This meta-analysis was more focused on studying nicotine per se, since previous studies had focused more on smokers and examined the effects of nicotine on the brain only after cessation of use. Another meta-analysis focused only on laboratory studies healthy people and excluded smokers who quit nicotine or those who were not included in the double-blind study compared with placebo. This meta-analysis pooled data from 41 studies and analyzed measures of immediate response (accuracy and reaction time) as well as response to stimuli (accuracy and reaction time), 76% of trials, and the meta-analysis itself were not associated with the tobacco industry (were independent ). Nine of these studies examined the accuracy of immediate reactions, and 8 of these studies plus 5 others examined reaction time. Only 5 (unique) studies examined stimulus response accuracy as well as stimulus reaction time, in addition to the other six studies. A significant and positive effect was observed for instantaneous response accuracy (g=0.34, z=4.19, p less than 0.001), instantaneous reaction time (g=0.34, z=3.85, p less than 0.001) and stimulus reaction time (g=0.30, z= 3.93, p less than 0.001). Non-significant improvements were observed for stimulus response accuracy (g=0.13, z=0.47, p less than 0.6). A strict linear dependence was observed regarding these parameters. Relative improvements in attention scores were observed with varying doses of nicotine in a dose-dependent paradigm. Improvements were observed in directing and maintaining attention to stimuli, accuracy, and when switching attention between stimuli, but improvements in accuracy of attention switching may not be as significant.

Anxiety and depression

In a study of patients with mild cognitive decline (non-smokers), use of nicotine patches at a dose of 15 mg daily for 6 months was associated with improvements in subjective anxiety scores, a measure of the anxiolytic effects of nicotine. The same study did not demonstrate significant improvement in subjective depression scores. One study using nicotine in non-smokers noted that a 2mg dose of nicotine (nicotine gum) caused increased activity in areas of the brain associated with negative perception compared to placebo. Thus, it is hypothesized that nicotine may increase anxiety.

Aphrodisiac

One study comparing regular and non-nicotine cigarettes found that cigarettes containing nicotine had a negative effect on sexual effects as measured through the bloodstream (penis diameter measurements were taken). Thus, it is hypothesized that nicotine may act as an anaphrodisiac. Two more recent studies in nonsmoking men and women found that nicotine may reduce sexual stimulation (induced by watching pornographic films or self-stimulating) without significantly affecting other mood parameters; men have also reported decreased erections after taking nicotine.

Nootropic effects

A meta-analysis of nicotine found that nicotine causes improvements in memory, especially short-term memory. A 6-month study of patients with mild cognitive impairment (over 55 years of age reporting memory lapses) found that daily use of 15 mg nicotine patches (release over 16 hours) was associated with improvements in memory, attention and psychomotor speed. reactions.

Fatigue

Nicotine has been shown to reduce brain fatigue in individuals with increased impulsivity (and decreased self-control), with little effect in individuals with decreased impulsivity.

Reward mechanism

In a study of non-smokers, 14 mg nicotine patches (two 7 mg patches) increased reward response to non-drug stimuli. The study used a sophisticated computer imaging test. Users given nicotine responded better to reward-related stimuli, and their reward mechanism lasted longer than the control group. The same conclusion was reached by researchers who gave smokers money after the test. Similar results were found in animal studies where nicotine administration was associated with an increase in reward response to non-drug stimuli. Nicotine cessation was associated with decreased reward responding.

Impulsiveness

In a study of smokers with problem gambling, it was noted that although taking 4 mg of nicotine (via an inhaler) suppressed cravings for cigarettes, there was no effect on problem gambling compared to placebo. When examining nicotinic acetylcholine receptors (which nicotine activates), using transdermal nicotine patches (7mg) and assessing impulsivity using three different tests, nicotine was observed to improve measures related to impulsivity in a group with increased baseline levels of impulsivity (lower self-control), with no significant effect on individuals low in impulsivity. At the same time, different indicators of reaction time were observed, the best indicators were recorded in the group with reduced impulsivity.

Neuroscience (Addiction)

Mechanisms

The current prevailing theory of the mechanisms of nicotine dependence is the activation of nicotinic acetylcholine receptors (nAChRs) on mesocorticolimbic dopaminergic neurons, which serve to enhance the response to rewards and motivation, as well as to non-pharmacological stimuli. The nootropic effect of nicotine also manifests itself through these mechanisms. Secondary to the activation of α4ß2 and ß2 nicotinic acetylcholine receptors on dopaminergic neurons, they depolarize, causing an increase in neuronal firing. Direct activation of α4ß2 nicotinic acetylcholine receptors directly excites these dopaminergic neurons. All of these mechanisms result in the influx of dopamine into the nucleus accumbens, which is also associated with the addictive mechanism underlying the action of substances such as heroin and cocaine. Inhibition of this dopaminergic process results in a reduction in nicotine-related cravings. Activation of a7 nicotinic acetylcholine receptors increases excitation through the nucleus accumbens from the ventral tegmental area (VTA), as well as in two other regions known as the pedunculopontine tegmental nucleus (PPT) and laterodorsal tegmental nucleus (LDT), as binding to presynaptic a7 nicotinic acetylcholine receptors increases glutaminergic activity and provides long-term potentiation. Unlike α4ß2 and ß2 receptors, which desensitize quite quickly after activation, α7 nicotinic acetylcholine receptors desensitize slowly, which ensures their long-term potentiation through an increase in glutaminergic signaling. In many cases, the inhibitory potential of GABAergic neurons is reduced. GABAergic neurons, which are expressed mainly in the ventral tegmental area, and when normal conditions They resist the excitation of glutaminergic neurons and express mainly α4ß2 receptors. When smokers chronically ingest nicotine and maintain elevated levels of nicotine in their bodies, these receptors are desensitized and their effects are reduced due to decreased α4ß2 activation, leading to a dramatic increase in α7 nicotinic acetylcholine receptors and glutaminergic neuron activation. Activation of dopaminergic neurons is directly related to many of the short-term effects of nicotine in this brain region, and activation of a7 nicotinic acetylcholine receptors on neurons other than this brain region strengthens the neuronal network and is a mechanism of long-term addiction. Dependent smokers exhibit increased dopamine release, which was absent in non-smokers in this study. When comparing nicotine per se and tobacco from cigarettes in dependent smokers who were pre-given a 4 mg nicotine lozenge versus placebo, and then when comparing smoking a cigarette without nicotine in both groups, it was shown that smoking cigarettes, regardless of their nicotine content, was associated with feelings of pleasure and decreased cravings, and that pre-administration of nicotine reduced the number of puffs and subsequently reduced cravings. Other studies have also confirmed these findings for nicotine-containing cigarettes.

Kinetics

One aspect of the reward mechanism of nicotine use is the speed at which nicotine reaches the brain and is associated with perceived reward. When smoked, nicotine can reach neural tissue within 10-20 seconds, faster than intravenous injections, which is comparable to intranasal nicotine. A rapid increase in neural nicotine concentrations is one of the factors of addiction. Other methods of nicotine administration that avoid such a rapid and rapid Cmax in neural tissue (gum, patches, sublingual tablets and lozenges) are associated with a lesser degree of dependence, however low rate addiction when consuming such products is also associated with the amount of absorbed dose of nicotine. The rate at which nicotine reaches the brain and the total concentration of nicotine reaching the brain are predictors of addictive potential. High doses and rapid absorption (from cigarette smoking) are associated with greater addiction than sustained-release forms of nicotine (gum, patches). One study of nicotine in smokers who wanted to quit noted that in a group that used nicotine gum (2mg or 4mg; n=127), 15mg transdermal patch (15mg; n=124), nasal spray (n=126) ) or nicorette inhaler (n=127) with ad libitum use of the products noted that among users who had not smoked for at least 3 weeks and completed a 12-week study, all methods were equally effective, relative to the number of smokers who continued their cessation smoking and average enjoyment or satisfaction over that time period. Dependence rates during nicotine replacement therapy were assessed by how many people continued to use nicotine 3 weeks after the end of the study (37% in the spray group, 28% in the gum group, 19% in the inhaler group, and 8% in the patch group), and on subjective dependence indications during this time period (33% inhaler, 22% gum, 20% nasal spray, 0% patch). When considering these endpoints According to the study, the use of nicotine gum is associated with lower rates of subjective dependence than the inhaler and nasal spray combined. The patch was associated with the lowest rates of dependence. Nicotine replacement therapy itself is associated with the development of addiction, which is related to the rate and total amount of nicotine consumed. The level of addiction is lower than that of smoking cigarettes.

Effect of nicotine on men and women

Nicotine cravings are associated with sexual dimorphism, since women require a smaller dose of nicotine to develop addiction, and smoking cessation is more difficult for women than for men. These differences have a biological basis, as studies of laboratory animals also show such differences. Low doses of nicotine (bordering the level at which rats may not self-administer nicotine, which is an indicator of addiction) have a greater effect on females than males. It was shown that females were willing to travel longer distances to obtain a dose of nicotine, compared to males. It is believed that hormones circulating in the body may play a role in these differences, since exogenous progesterone is associated with reduced cravings and the enjoyment of smoking. Additionally, there has been some correlation of nicotine with the estrous cycle as it relates to the development of nicotine addiction, as women report increased cigarette use during menstruation. This phenomenon is independent of menstrual symptoms (eg, smoking to relieve menstrual symptoms). However, some studies have failed to demonstrate this association. Particular sensitivity to smoking cessation develops during menstruation and some time after its end. These interactions may underlie the ability of nicotine to interfere with estrogen signaling in neural tissue by directly inhibiting the beta subunit of the estrogen receptor and inhibiting aromatase.

Nicotine and the development of addiction

19.8% of the American population smoke cigarettes (not nicotine per se) (2007 data), and although 45% of smokers tried to quit (2008), only 4-7% succeeded. During smoking cessation, one of the common side effects reported by respondents was difficulty concentrating. One of the most common reasons for smoking resumption was the subjective nootropic effects of nicotine. For these reasons, nicotine has long been studied in relation to the development of dependence on tobacco cigarettes.

The cardiovascular system

Heart rate

When a 21-year-old man took 6 mg of nicotine gum, there was an increase in heart rate, as well as an increase in diastolic and systolic blood pressure 30 minutes after use. The same study in women also showed an increase in heart rate, but did not show a significant increase blood pressure. A 6-month study using nicotine patches at a dose of 15 mg showed a significant reduction in blood pressure, with a mean increase of 9.6 mmHg in the placebo group. in 6 months. In the group using nicotine patches, a decrease in systolic pressure of 4 mmHg was observed.

Interactions with glucose metabolism

Inflammation and glucose metabolism

Secondary to the anti-inflammatory effects of nicotine, nicotine may enhance insulin sensitivity if the mechanism of insulin resistance is related to inflammation, and in rats nicotine affects insulin without affecting body weight.

Research

Cigarette smoking per se may have a negative effect on glucose metabolism. Long-term use of nicotine gum correlates with insulin resistance. In this regard, the effect of nicotine per se is very interesting in terms of research. When looking at the effects of nicotine in isolation in healthy smokers, it was noted that use of a 14mg nicotine transdermal patch increased insulin resistance and blood glucose levels. Nicotine infusions in non-smokers had no effect on baseline glucose uptake levels in healthy individuals (10.9+/-0.3mg/kg LBM), and in type II diabetics uptake was impaired by approximately 32+/-6%. Thus, nicotine has been shown to have different effects on healthy individuals and diabetic patients. These data support previous research that suggests that nicotine use in diabetics worsens insulin resistance, while a study using snuff noted that in healthy individuals, tobacco per se was not associated with the development of insulin resistance, as opposed to smoking; thus, a compound found in cigarettes rather than snuff may be associated with the development of insulin resistance, and this compound is not nicotine per se. In this study, where smokers were divided into “healthy” and “diabetic” groups, the division was based on circulating levels of glucose, insulin and HbA1c (elevated in diabetics); The nicotine dose was 0.3 µg/kg/min, and simulated cigarette smoking. 6.3. Insulin sensitivity after smoking cessation It is known that weight gain, usually fat, is common after smoking cessation; this is due to both decreased metabolism and increased caloric intake, although it may also be due in part to increased insulin sensitivity after smoking cessation. Nicotine patches have no effect on increasing insulin sensitivity after smoking cessation.

Obesity

It is known that cigarettes can stimulate lipolysis (fat burning). This effect can also be reproduced by intravenous administration of the same doses of nicotine; When comparing monozygotic twins, the weight of smoking brothers/sisters was 2.5-5.0 kg less than the weight of non-smoking brothers/sisters. Although weight can be influenced by a variety of factors, stimulation of lipolysis and excitation of the cholinergic neuron in adipose tissue are direct fat-burning effects that occur through nicotinic acetylcholine receptors.

Mechanisms

Nicotine may enhance AMP-dependent kinase activity in adipocytes, which is associated with increased lipolysis in a time- and concentration-dependent manner. Since the increase in AMP-dependent kinase and lipolysis were inhibited by N-acetylcysteine, they were mediated by pro-oxidative effects. Oxidative stress is known to regulate AMP-dependent kinase, particularly peroxynitrate (a pro-oxidative derivative of nitric oxide), and these effects were observed at circulating nicotine levels achieved through smoking a single cigarette (6nM, increasing to 600nM). However, activation of AMP-dependent kinase does not induce lipolysis with nicotine (as the inhibitor, compound C, successfully inhibited AMP-dependent kinase but did not abolish lipolysis). The increase in lipolysis with nicotine is due to nicotine inhibiting fatty acid synthase (by 30% at 100 nM), which may be secondary to peroxynitrate, and a possible increase in catecholamines, such as epinephrine, that are released in response to nicotine stimulation ( which was shown after intravenous use). The study notes that 7.2ng/ml nicotine (levels achieved after smoking a cigarette) increased epinephrine and norepinephrine levels by 213+/-30% and 118+/-5%, respectively. Glycerol release (144-148%) was inhibited by a cholinergic agonist (acting at the acetylcholine receptor) and was reduced by 60% by propanolol (a beta-adrenergic antagonist involved in the release of catecholamines). A reduction in nicotine-induced lipolysis has also been observed in other studies with concomitant beta-adrenergic receptor blockade. Nicotine acts on acetylcholine receptors, releasing epinephrine and norepinephrine, which then act on beta-adrenergic receptors (the molecular target of adrenaline and ephedrine), affecting fat burning processes. This is not the only, but the most important mechanism of action of nicotine. Activation of nicotinic acetylcholine receptors on fat cells is associated with decreased secretion of pro-inflammatory TNF-a, and this receptor (namely a7nAChR) is negatively correlated with body fat mass; People with a body mass index (BMI) of 40 or higher have up to 75% less mRNA and protein content than people of normal weight. Activation of nicotinic acetylcholine receptors on fat cells mediates anti-inflammatory effects in the fat cell, and decreases the secretion of pro-inflammatory cytokines.

Metabolism

In healthy people, nicotine gum containing 1-2 mg of nicotine increases the metabolic rate by 3.7-4.9%. These figures increase even more with the simultaneous use of 50-100 mg of caffeine in chewing gum, without the dose dependence observed with caffeine addiction. The rate of fat oxidation does not change when taking nicotine compared to the control group. The measurements were carried out for 180 minutes, during the first 25 minutes the subjects chewed gum.

Research

In rodents, nicotine can reduce fat weight when fed either a high-fat diet or a regular diet. In both cases, blocking of this effect was observed when taking the acetylcholine receptor antagonist mecamylamine; One study showed that selective inhibition of the α4ß2 receptor (using varenicline) could only partially inhibit fat loss. In experiments on rats, it was shown that the fat burning effect is observed with controlled food intake, without reducing calories. These studies, however, use very high doses of nicotine (2-4mg/kg, one study used doses up to 4.5mg/kg, equivalent to 2.5 packs of cigarettes). These changes were observed at doses of 0.5 mg/kg orally and were dose-dependent, but their statistical significance may decrease over time (as effectiveness decreases). In one study of male smokers (unresponsive to the effects of nicotine) who were given 4mg nicotine gum or an equivalent dose via cigarette or inhaler, there was no increase in lipolysis over 180 minutes, nor was there an increase in epinephrine levels. Regarding metabolic rate, several studies have observed increased metabolism in rats when given isolated nicotine. People who smoked cigarettes experienced an increase in metabolic rate of approximately 210 kcal per 24 hours compared to non-smokers. This increase in metabolic rate may be mediated by simply increasing the amount of epinephrine and norepinephrine, with a half-life of 3.5 minutes (similar to the active half-life of adrenaline receptors). The increase in lipolysis does not show an obvious half-life. Animal studies show a significant increase in lipolysis and metabolic rate, which decreases over time (at low doses, nicotine is not very different from placebo, and only at high doses is lipolysis observed). The increase in metabolism may simply be due to an increase in the amount of catecholamines (adrenaline and norepinephrine). One study using nicotine patches in 55-year-old men and women found that after 91 days of nicotine use there was a 1.3kg weight loss (0.13kg in the placebo group). However, when measured again after 6 months, the difference disappeared. Human studies show that using nicotine in isolation for long periods of time is not effective for weight loss.

Weight gain

Quitting the habit of smoking cigarettes is often accompanied by weight gain, mainly fat mass, which is associated with a slower metabolism and increased food consumption. Nicotine itself (to a small extent) may help reduce weight gain after quitting smoking, but results have been mixed and this cannot be proven with certainty. Nicotine gum, for example, may not counteract weight gain after quitting smoking (2 mg gum; no dose limit). One study demonstrated benefits when using 2-4 mg gum in a specific regimen. A dose-dependent effect is possible (which was not confirmed later in experiments with nicotine patches). Compounds that may help prevent weight gain after quitting smoking include naltrexone, dexfenfluramine and phenylpropanolamide, as well as fluoxetine.

Skeletal muscles

Mechanisms

Nicotine has been shown to be able to activate mTOR when incubated in skeletal muscle culture, possibly mediating the decrease in insulin sensitivity associated with smoking (as mTOR activation induces IRS-1 and suppresses insulin signaling).

Effect of nicotine on inflammatory processes

Mechanisms

Nicotine exhibits anti-inflammatory properties by acting as a cholinergic agonist by activating the a7 nicotinic acetylcholine receptor (a7nAChR) at immune cells, in particular, dendritic cells and macrophages. This pathway is naturally regulated by the neurotransmitter acetylcholine, released from vagus nerve, which inhibits the ability of immune cells to respond to TNF-a and reduces its release from immune cells. It was also later demonstrated that nicotine can inhibit NF-κB activation in LPS-activated macrophages and also affect splenocytes. It appears that activation of the nicotinic receptor by either nicotine itself or the neurotransmitter acetylcholine can suppress inflammatory responses on immune cells and reduce the secretion of pro-inflammatory cytokines. Activation of a7nAChR by nicotine increases the release of JAK2 and STAT3, which in turn causes the release of tristetraproline (TTP), which destabilizes TNF-a and interferes with its action. TTP is a low-efficiency cytoplasmic regulator of inflammation, and its absence causes arthritis in rats. Another possible mechanism of action of nicotine is the inhibition of high mobility group 1 proteins, which may be a possible mechanism for reducing the clinical signs of sepsis.

Ulcerative colitis

Epidemiological studies have shown that smokers have a reduced risk of developing ulcerative colitis. The relative risk is 0.6 (0.4-1.0) when compared with non-smokers. People who quit smoking have a twofold increased risk of developing UC compared to smokers (1.1-3.7). Similar data have been found in other studies, however, these figures do not extend to other gastrointestinal diseases such as Crohn's disease (sometimes associated with an increased risk) and inflammatory disease intestines. It was noted that ulcerative colitis develops more often in those who quit smoking than in those who currently smoke. These paradoxical effects are secondary to the fact that nicotine acts as an anti-inflammatory alkaloid. Even when consuming nicotine through cigarettes, there is an inverse relationship with the development of ulcerative colitis.

Nicotine and cancer

Metabolites

N′-nitrosonornicotine (NNN), a nitrosamine found in tobacco, a metabolite of nornicotine, may have carcinogenic potential. NNN was found in the urine of people who quit smoking and used nicotine patches or gum. It has been suggested that some individuals may produce NNN ecdogenously from nicotine. One study using 21mg nicotine patches for 24 weeks after smoking cessation noted that urinary NNN levels dropped to levels close to the detection limit (0.005pmol/ml-0.021pmol/ml). The study also noted that 40% of passive smokers (out of 10) had urinary NNN levels of 0.002 pmol/ml, and although these two studies (the latter of which was well-designed) noted a significant increase in urinary NNN levels, at least , one study showed no increase with nicotine replacement therapy (using patches).

Lungs

Activation of the α7 acetylcholine receptor promotes anabolic effects such as Akt phosphorylation and Src activation. Activation of the nicotinic receptor increases cytoplasmic markers of pro-inflammation (5-LOX, COX-2 and NF-kB translocations). Nicotine at a concentration of 100 nM cannot induce proliferation, but may exhibit anti-apoptotic effects. Cholinergic receptors act as a cell survival signaling pathway in lung cancer, which also applies to acetylcholine.

Interaction with hormones

Testosterone

Nicotine and its metabolite cotinine negatively affect testicular structure and circulating testosterone levels, and may reduce the number of androgen receptors expressed (rat study, prostate measurements). Some of these mechanisms are secondary to testicular oxidation (including damage and enzyme depletion), but some suppression may be secondary to cholinergic agonism in the testes. Similar mechanisms operate for nicotine and cotinine. One study using doses of 0.5 mg/kg and 1 mg/kg via gavage (into the stomach) for 30 days noted a decrease in testicular weight associated with nicotine use. There was no clear effect on prostate hypertrophy. A decrease in circulating testosterone levels was observed in a dose-dependent paradigm, but returned to normal after 30 days of nicotine withdrawal. In a study using a lower dose, 0.6 mg/100 g, for 12 weeks, there was also a decrease in testicular weight and suppression of circulating and testicular testosterone levels. The amino acid taurine was able to halve the decline in testosterone levels at a dose of 50 mg/kg body weight. A greater effect was observed when using human human chorionic gonadotropin. Nikitin can reduce the release of 17ß-HSD and 3ß-HSD and StAR expression to 60% of the control group. These effects may be reduced by taking taurine and normalized by taking human chorionic gonadotropin. Finally, another study using mice aged 20 weeks ( average age), when taking nicotine in low doses (0.0625 mg/kg body weight) after a short initial phase, noted that, after 90 days, there was a suppression of testosterone levels from 898.4 ng/ml in the control group to 364 ng/ml (59.5% reduction). ) in the nicotine group, which was associated with abnormal cell organization in the prostate. Similar results have already been obtained previously. This is thought to be due to decreased androgen levels, although the exact cause is still unknown. In a rat study, suppression of testosterone levels was observed with nicotine at psychologically relevant doses, which is partly due to receptor activation (muscarinic cholinergic) and, in chronic situations, testicular damage due to oxidation; the damage was partially reduced by the use of antioxidants. One study of men considered nicotine dependent while smoking 15.48 mg nicotine (equivalent to serum levels of 20 ng/mL or higher) showed no change in circulating testosterone levels when measured over two hours, although there was a trend towards a decrease. Another study in Medline was a cohort study of men aged 35-59 years (n=221) who were daily smokers before the study. Circulating testosterone levels were assessed in these men after a year of abstinence. Measurements of baseline testosterone levels were shown to be similar one year after smoking cessation. A larger study in older men (n=375, age 59.9+/-9.2 years) shows that smoking is associated with increased testosterone levels. Other studies show no significant difference between groups, or even a trend towards more high levels testosterone in smokers (4.33+/-0.53ng/ml in non-smokers, 4.84+/-0.37ng/ml in smokers).

Estrogen

In experiments with baboons, nicotine was shown to be an aromatase inhibitor in vivo after injections of nicotine into baboons at concentrations of 0.015-0.03 mg/kg (plasma levels reached 15.6-65 ng/ml), as after smoking a cigarette. These data contradict previous studies showing that nicotine is a potent aromatase inhibitor in vitro. This may explain why women who smoke heavily are often susceptible to estrogen deficiency disorders (osteoporosis, menstrual disorders, early menopause) and explain the increased levels of circulating testosterone in smokers of both sexes (which has not been demonstrated in short-term studies). The ability of nicotine (and related nicotine alkaloids) to inhibit the aromatase enzyme may cause a shift toward androgens rather than estrogens over time. The degree of change observed in these studies may be greater than with nicotine alone due to the presence of other alkaloids in tobacco. In a study of estrogen levels in rat serum, it was shown that circulating estradiol levels decreased over an average of 4 estrous cycles compared with controls 4 days later. Some differences were observed in the degree of reduction. Estrogen partially protects against damage resulting from ischemia (lack of oxygen) and reperfusion (reintroduction of oxygen), and this protection is suppressed by long-term nicotine use. A later study identifying the mechanisms underlying this noted that rats given nicotine hydrogen tartrate at a dose of 4.5 mg/kg (to produce effects identical to chronic cigarette smoking) for 16 days before cerebral ischemia experienced increased damage caused by ischemia when consuming nicotine (oral contraceptives, harmless individually, acted in synergy with nicotine, increasing the damage). These effects were thought to be mediated by estrogen inhibition of intracellular estrogen signaling, and since these effects were also seen with 1 µM ICI 182780, it was argued that nicotine inhibits estrogen receptors and CREB phosphorylation, which mediates the neuroprotective effects of estrogen (by inhibiting NADPH oxidase and reducing pro-oxidation in cage); Nicotine reduces the amount of ER-ß protein but not ER-a, and this inhibition of ER-ß has also been implicated in reducing neuronal plasticity and mitochondrial loss in neurons.

Luteinizing hormone

In rats, when given nicotine at a dose of 0.6 mg/100 g body weight for 12 weeks, levels of luteinizing hormone and follicle-stimulating hormone are reduced by 40% and 28%, respectively. In one human study, when assessing LH levels for two hours after administration of 15.48 mg nicotine (via smoking in dependent smokers), it was noted that LH levels increased within 14 minutes of cigarette smoking and were highly correlated (r=0.642) with serum levels nicotine

Prolactin

Cigarette smoking in dependent smokers is associated with an increase in prolactin levels within 6 minutes of cigarette smoking. Levels remain elevated for another 42 minutes and then return to normal within 120 minutes.

Interaction with other substances

Nicotine and caffeine

The combined use of caffeine and nicotine (coffee and cigarettes) is very popular; Smokers are also much bigger coffee drinkers than non-smokers. When used together in large doses, nicotine and caffeine exhibit a thermogenic effect (440 mg of caffeine and 18.6-19.6 cigarettes per day). This thermogenic effect is further enhanced by exercise, but one study indicates that this phenomenon is only observed in men. One study noted that using 50-100mg coffee and 1-2mg nicotine gum produced greater appetite suppression than nicotine alone. Use of this combination in high doses (100 mg caffeine and 2 mg nicotine) may be associated with nausea. One study showed that caffeine (250 gm) administered to 4-week caffeine-naïve smokers with nicotine infusions resulted in a decrease in the perceived stimulant effects of nicotine compared to placebo. In people who do not smoke but consume caffeine, there is no significant interaction between caffeine and nicotine. One study (self-reported) noted that caffeine did not increase nicotine addiction potential when both were used in adequate doses. These results, however, contradict another study in which participants were asked to decide how much money they were willing to spend on caffeine or nicotine injections. This study showed that caffeine's ability to reduce the "negative" effects of nicotine stimulated increased addiction. Nicotine replacement therapy (to reduce nicotine cravings) has no effect on caffeine withdrawal or caffeine dependence.

Nicotine and alcohol

Alcohol (ethanol) is a popular drink in society. Alcohol is popular among people who smoke, and vice versa. In addition, the use of nicotine stimulates alcohol consumption, especially in men. In a study evaluating the combined use of alcohol and nicotine, it was noted that nicotine (10 µg/kg) significantly suppressed subjective perception alcohol intoxication(alcohol level in exhaled air is 40-80 mg%), but increases alcohol-related memory deficits. The sedative effect of alcohol may be reduced by nicotine consumption. Nicotine can increase the euphoria of drinking alcohol. This decrease in short-term memory has been reported previously, with the group taking the combination of alcohol and nicotine performing worse than both the placebo group and the group taking alcohol alone. Alcohol, nicotine, or a combination of these substances do not have a significant effect on attention scores.

Nicotine and N-acetylcysteine

N-acetylcysteine ​​(NAC) is a bioactive form of the amino acid cysteine ​​(found in large quantities in whey protein) that has been studied as a substance that may reduce nicotine addiction. The theory about the role of NAC in addiction is based on glutamate transmission. Failure during drug withdrawal addictive, is associated with a decrease in basal concentrations of extracellular glutamate. This results in decreased activation of presynaptic mGluR2/3 receptors, which normally suppress glutamate signaling, and an increase in glutamate signaling; Although most studies have been conducted in cocaine models, these receptors are also activated in nicotine addiction. Stimulating these receptors reduces the “positive” effect of nicotine. Increasing extracellular glutamate levels reduces withdrawal symptoms. NAC may reduce withdrawal symptoms, increase extracellular glutamate levels, and to some extent suppress addiction to cocaine and heroin in rats. One double-blind study of smokers (15 or more cigarettes per day) who quit smoking abruptly and then took either placebo or NAC twice daily for a total dose of 3,600 mg did not show a reduction in nicotine cravings when taking NAC. The reduction in side effects was small and did not reach statistical significance. However, when the subjects were invited back to the laboratory and asked to smoke (which signaled the end of the trial), the subjects who were given NAC reported a significant decrease in the enjoyment of smoking compared to the control group. On a scale of 1 to 100, the placebo group rated the enjoyment of smoking a cigarette as 65.58+/-24.7 and NAC as 42.6+/-29.02 (35.1% less). This reduction in positive effects may apply more to people who smoke than to those who quit. One study (double-blind) noted that NAC at a dose of 2,400 mg per day for 4 weeks in smokers did not reduce the number of cigarettes smoked per week per se, but social situations(smoking combined with drinking) there was a significant decrease in the number of cigarettes smoked; these effects were more pronounced when using NAC for 4 weeks or more.

Nicotine and St. John's wort

St. John's wort is a dopamine antidepressant being investigated as an anti-nicotine addiction compound due to its positive effects in mice and mechanically reducing addiction through modulation of catecholamines (dopamine, norepinephrine, epinephrine). Buproprion (an antidepressant) is an effective smoking cessation aid. The first open-label (non-blind) trial of St. John's wort for nicotine addiction found that St. John's wort at a dose of 900 mg daily for three months was associated with a 24% abstinence rate at the end of the study. This was followed by another double-blind study of St. John's wort 300 mg and 600 mg three times daily (total dose 900 mg or 1800 mg; 0.3% hypericin) for 12 weeks against placebo, in which St. John's wort showed no significant difference from placebo.

Nicotine and modafinil

Modafinil is a prescription drug for narcolepsy with nootropic effects that is being studied as a treatment for reducing nicotine dependence. In one blinded study, modafinil not only failed to reduce withdrawal symptoms, but actually increased negative nicotine withdrawal symptoms. When modafinil was taken for 8 weeks at a dose of 200 mg in the morning, the dropout rate was 44.2% in the placebo group and 32% in the modafinil group (not significant). Modafinil use is also associated with a significant increase in depressive symptoms and bad mood, without affecting positive mood and desire to smoke.

Nicotine and taurine

Taurine is a nonessential amino acid that contains a sulfur group. Taurine reduces (but not completely) the decrease in testosterone and other hormones (luteinizing hormone, follicle-stimulating hormone) observed with nicotine use in rats. Taurine has been studied for this purpose because it is the most abundant free ß-amino acid in the male reproductive system and exhibits protective effects against the effects of nicotine on cardiac tissue, as well as the bladder and urinary tract, due to its antioxidant properties.

Nicotine and ephedrine

In one study using nicotine (0.2 mg/kg) in rats, which did not find any negative effects on cardiac tissue when nicotine was taken in isolation, small toxic signs were found when taking a combination of caffeine and ephedrine in the presence of nicotine; This study used fairly large doses of ephedrine (30 mg/kg) but adequate doses of caffeine (24 mg/kg) and nicotine. A dose of 0.2 mg/kg in mice is approximately equivalent to a dose of 3 mg in a 90 kg human.

Safety and toxicity

A study using nicotine patches at a dose of 15 mg for 6 months in otherwise healthy people aged 55 years with slight memory impairment found that total negative effects significantly increased with nicotine (82) than with placebo (52), but neither effect was characterized as “severe.” The study also reported a decrease in blood pressure and an increase in cognitive performance when taking nicotine.

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List of used literature:

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Nicotine is one of the most famous alkaloids. It is he who is mentioned when talking about the dangers of smoking, saying that just one drop of the substance can easily kill a large horse. But is it?

What is nicotine and how poisonous is it? Is it possible to be poisoned by this alkaloid at home and how to help the victim if poisoning has occurred?

Chemists classify nicotine as alkaloids—nitrogen-containing substances of plant origin. This group also includes caffeine, quinine, strychnine, cocaine and some other organic compounds.

Many of them have a common feature - the ability to influence processes occurring in the body. Some alkaloids are considered poisons and at the same time medicines, it all depends on the amount of the substance. Nicotine can also be a medicine, but it is much more often referred to as a dangerous toxin.

The chemical formula of this substance is C 10 H 14 N 2. In appearance it is a clear oily liquid, which darkens and becomes yellowish-brown during storage. The smell of the substance is pungent and the taste is burning. The density of nicotine is practically no different from that of water, so it mixes well with it. With acids it forms salts, which are also highly soluble in water.

Nicotine is a poison that is extremely dangerous for insects and cold-blooded animals. Therefore, a century ago it was used as an insecticide. Later it was proven that this substance is also dangerous for humans and other warm-blooded creatures. Therefore, it was replaced by more harmless artificial derivatives, such as imidacloprid or acetamiprid.

Where can you find nicotine

Everyone knows that nicotine is in tobacco, but it is also found in other plants of the nightshade family, for example, in the familiar tomatoes and peppers. But its concentration there is low, so it does not threaten humans. There are traces of nicotine in other plants, for example, horsetail, clubmoss or sedum.

Nicotine alkaloids can also be found in coca leaves. More of this substance than in tobacco can be found only in a plant very close to it - shag.

But the human body normally does not contain nicotine. He does not take part in normal metabolic processes. Theoretically, under the influence of certain enzymes, this substance can turn into nicotinic acid. It is known as vitamin PP, the deficiency of which causes pellagra. But the human body does not have enzymes that can metabolize this toxin and convert it into a vitamin.

Although nicotine is a completely alien substance human body, it is very easily absorbed through the lungs from tobacco smoke, from the digestive tract when swallowed, and even through the skin upon contact with a sufficiently concentrated solution. Once in the blood, this alkaloid quickly spreads throughout the body.

It easily penetrates the blood-brain barrier, the placenta and other barriers. Therefore, smoking during pregnancy is strictly contraindicated; the toxin penetrates into the baby’s blood.

After inhaling cigarette smoke, nicotine reaches the brain within 4-7 seconds. Its maximum concentration is observed approximately 10 minutes after smoking. Its reduction by half occurs only after half an hour. At the same time, the alkaloid leaves the brain.

Nicotine is excreted very slowly by the body. It disappears from the blood in about 2-3 hours. But the products of its breakdown can be detected in the body for another day and a half to two days. The fact is that in the liver, nicotine is broken down into cotinine and nicotine-N-oxide. These substances are excreted by the kidneys, and cotinine can be detected in urine using a test even two days after smoking a cigarette.

After penetration into the blood, this alkaloid affects the nerve endings, which determines its effect. In low concentrations, it acts on acetylcholine receptors, causing the following effects:

• Increased adrenaline production;
• Increase in blood pressure and vasoconstriction;
• Increased heart rate;
• The entry into the blood of glucose stored in the liver in the form of glycogen;
• The release of substances in the brain that form a psychostimulating effect.

After this, slight dizziness appears, which for some is accompanied by almost imperceptible derealization, for others it resembles flying. For many people, a cigarette helps them concentrate and collect themselves. But this doesn't always happen. Often the first cigarette smoked causes nausea, headache and disgust.

If you increase the dose of nicotine, nerve synapses will begin to be inhibited, which can trigger the appearance of unpleasant symptoms. Although it is this effect that makes cigarettes the main sedative for many people.

Nicotine is considered to be a drug. Indeed, if you smoke a lot and for a long time, psychological and physical dependence develops. But it has not yet been established whether it is caused by nicotine or other substances in cigarette smoke. For many people, addiction develops only psychologically or does not appear at all.

Toxic effects of nicotine

Pure nicotine is a strong poison. Just 0.5–1 mg/kg of this substance is enough to kill a person. To assess its toxicity, it is worth saying that the lethal dose of the well-known potassium cyanide is much less and is 1.7 mg/kg. But while smoking most of of the toxin contained in tobacco flies away with the smoke and only about 20-30% enters the lungs.

Considering that cigarettes rarely contain more than 0.8 mg of nicotine, it is difficult to get serious poisoning from smoking.

Cases of fatal poisoning from smoking have been recorded in medicine. But these were competitions or bets between smokers and they “smoked” with cigarettes or pipes.

To significantly worsen your health, sometimes it is enough to smoke several cigarettes in a row. But you shouldn’t attribute all unpleasant symptoms to the effects of nicotine. There are others in tobacco harmful substances that can have a negative impact on human health. Common symptoms of nicotine poisoning include:

• Paleness and dizziness;
• Heart rhythm disturbances;
• Excessive agitation or apathy;
• Chills and cold sweat;
• Blurred vision and ringing in the ears;
• Nausea, drooling and vomiting;
• Diarrhea;
• Weakness.

In the most dangerous situations convulsions may begin.

It should be noted that although the likelihood of nicotine poisoning from smoking is minimal, this habit cannot be considered harmful. Long-term exposure to small doses of the toxin leads to damage to almost all body systems - respiratory, cardiovascular, digestive, etc. Smokers are at risk of developing gastritis, atherosclerosis, arrhythmia and coronary disease heart, lung cancer and many other diseases.

Intoxication with the alkaloid nicotine can be acute or chronic. The first type occurs in those who have not smoked before (or almost never smoked) and suddenly received a large dose of the substance. All the symptoms described above usually appear in them. Chronic poisoning occurs in experienced smokers.

Smokers rarely suffer from nicotine toxicity. This can happen if you smoke for a very long time and a lot. In such a situation, the toxin settles on the mucous membranes respiratory tract and it heats up there. Having reached critical quantity, it causes poisoning. Usually, experienced smokers do not immediately notice unpleasant symptoms and therefore delay going to the hospital, aggravating the situation.

You can become seriously poisoned by nicotine if you swallow it. Adult chewing tobacco users usually control the amount they consume. But a child, having found a cigarette or tobacco, can taste it and get seriously intoxicated. Sometimes symptoms of poisoning appear very quickly in acute form, so the child has to be saved in a hospital setting.

You can get severe nicotine poisoning, even fatal, by drinking an insecticide containing it. But you are unlikely to be able to find a suitable composition, since they have long been considered obsolete.

Passive smoking can also cause poisoning if you have to spend a lot of time in a smoky room. Previously, tobacco factory workers often suffered from this. But modern precautions have eliminated this possibility.

How to help a person with nicotine poisoning

It is not easy to independently determine that a person has been poisoned by nicotine. Therefore, it is better to call doctors immediately.

While waiting for an ambulance, you can try to rinse your stomach if the substance was swallowed and then drink enterosorbent. If the toxin entered through another route, it is enough to provide the victim with a comfortable position and peace. In case of severe tremors or convulsions, it is necessary to ensure that the patient does not harm himself.

You should not give the victim any medications other than enterosorbents. It is difficult for a non-professional to predict how this or that drug will affect a person’s condition. It is better to just stay with him and try to support him until the doctors arrive.

Treatment of poisoning

In most cases, no treatment is required for those who are poisoned. Gradually all the unpleasant symptoms go away, leaving only an aversion to tobacco.

If poisoning occurs with concentrated nicotine, for example, in an insecticide, such intoxication is treated in a hospital setting. Usually maintenance therapy and cleansing of the body is required.

The benefits of nicotine

The toxicity of many substances depends on their concentration and method of application. This also applies to nicotine. Tablets, chewing gum and patches with this substance help you quit smoking.

There are also studies being conducted in which nicotine is used as a treatment for ADHD, Alzheimer's and Parkinson's diseases, shingles and many others. Perhaps, over time, nicotine will become the basis for new drugs and begin to benefit humanity.