24 August 2012

The harm of smoking in all details

"The joys of nicotine are not available in everyday life"
There is no pronounced intoxication from nicotineAbout the fact that nicotine addiction is drug addiction, about the positive effect of nicotine on cognitive processes and thinking, about why cigarette smoke is inhaled with the lungs and cigar smoke with the mouth, and about the genetic predisposition to nicotine addiction in a lecture on "Gazeta.

Ru" says Pavel Beschastnov, a psychiatrist, psychotherapist, narcologist, director of the scientific and methodological center of the consulting company "Contact Expert".

Nicotine: basic informationNicotine addiction is in fact a common drug addiction, not much different from alcohol, heroin, amphetamine or any other.

After such a dashing statement, it is worth slowing down a little and marking such a moment. In Russia, even in academic and scientific literature, the words "drug addiction" and "substance abuse" are easily used, while in Western sources these terms have not been used since the 60s: the expressions "drug abuse", "substance dependence", "addiction" are used (and the word "addiction" is also gradually coming out of appeals). Currently, "drug addiction/substance abuse" is a common everyday philistine vocabulary, the terms have no clinical meaning. In Western medicine, these words are not used, for example, Wikipedia does not even have such an article – "narcomania", and from the Russian article "drug addiction" the English analogue throws out "substance dependence". Therefore, some assumptions, simplifications and quotation marks should be kept in mind. It's not drug addiction or substance abuse – it's addiction.

So. Tobacco smoking is an addiction as an addiction. The only caveat is that there is no pronounced intoxication from nicotine, there is no deformation of personality and there is no social degradation, therefore smoking is traditionally considered as a bad habit, and not as a disease. But in fact, addiction is like addiction. One good thing: nicotine is practically harmless. It can cause trouble with acute overdoses (which in practice happens extremely rarely), at long distances, with chronic abuse, the harm to health is doubtful or absent.

Tobacco smoking accounts for most of the nicotine consumed in the world. In addition to nicotine, tobacco smoke contains from 2500 to 4000 different compounds. Almost all of them are toxic, carcinogenic and extremely dangerous. The main array of the adverse effects of tobacco smoking known to us is just the result of inhaling these combustion products of tobacco leaf and resins, but not nicotine itself. That is, such a "division of labor": dependence on nicotine – harm from all others.

The gaseous mixture makes up 95% of the total mass of tobacco smoke, it contains about 500 compounds, including nitrogen, ammonia, carbon monoxide, carbon dioxide, prussic acid and benzene. In the gas fraction, a suspension of solid particles flies – 5% of the mass of smoke and about 3,500 compounds, mainly nicotine plus several less significant alkaloids of the nicotine series: nornicotine, anatabine, anabazine. Everything else is aromatic hydrocarbons, nitrosamines, aromatic amines: there are thousands of them, and all are toxic and carcinogenic.

In light cigarette tobacco, the pH value of hydrogen, which characterizes its acidity, is 5.5. Nicotine is presented there in ionized form, it is not absorbed in the oral cavity, but is absorbed into the lung tissues. In black tobacco (pipe and cigar), nicotine is not ionized and has an alkaline reaction (pH 8.5), therefore it is able to be absorbed in the oral cavity. That is why cigarette smoke is inhaled with the lungs, and cigar smoke is inhaled with the mouth.

The peak concentration in blood plasma is reached quickly, nicotine reaches the brain within 10-19 seconds (for chewing tobacco and nicotine patches, the plateau is reached much longer, about half an hour). The body assimilates about 90% of nicotine from cigarette smoke, the half-life is 2 hours, the full cycle of metabolism is 6 hours.

A third of the received nicotine is excreted unchanged, the rest diverges in different ways, mainly (80% of the metabolized nicotine) through conversion to katinin. Katinin is an active metabolite of the nicotine series, but its effect is much weaker. In general, the products of nicotine metabolism have no significant effect on the body and are of no interest to us.

How nicotine worksThe point of action of nicotine is the nicotine acetylcholine receptor.

Acetylcholine receptors are one of the most important receptors in all vertebrates (including humans). They are muscarinic and nicotinic. The N-cholinergic receptor (nACh receptor) consists of five proteins. These proteins come in four groups – alpha, beta, gamma and delta, we are primarily interested in alpha and beta. Each of these proteins, in turn, exists in varieties – seven types of alpha subunits and four types of beta. Thus, by combining five proteins from this set, we obtain many subspecies of the nACh receptor. At least five variants are presented in the human brain – nicotine acts on everything, but with different intensity. The receptor consisting of three alpha4 and two beta2 subunits has the highest sensitivity to nicotine. These receptors are mainly located on the bodies of dopamine neurons involved in the reward system (the area of the VTA brain tire and the nucleus accumbens NACcore), and it is through them that the mechanism of nicotine addiction is realized.

In humans, alpha4beta2 receptor proteins are encoded on the fifteenth chromosome, there is a variant of this genetic cluster in which the predisposition to nicotine addiction is significantly higher. In addition, in mice with blocked alpha4 and beta2-coding genes, nicotine consumption in the experimental model is significantly reduced.

Is nicotine good on its own? Good is not the right word. Nicotine is a miracle how beautiful. By themselves, H-cholinergic receptors are not excitatory, but they modulate and affect other activating neurotransmitters. Nicotine provokes the release of dopamine and glutamate (the main excitatory neurotransmitter of the brain), to a lesser extent – serotonin and catecholamines (adrenaline and norepinephrine). Thus, nicotine has a positive effect on cognitive processes and thinking, concentration and attention, stabilizes the emotional background, increases resistance to stress factors, has an anti-anxiety effect, accelerates reaction, improves selective auditory and visual sensitivity.

Currently, many drugs of this class are in development. Marketers of pharmaceutical companies call them "acetylcholine modulators" in order to avoid bad connotations with tobacco, but in fact they are derivatives of the good old alkaloids of the nicotine series. It is assumed that they can be useful in the treatment of hyperactivity and attention deficit disorder in adolescents and adults, the treatment of Alzheimer's disease, Parkinsonism, some forms of epilepsy, ulcerative colitis, depressive and anxiety disorders.

Non-smokers who were given to inhale nicotine water vapor (relative to placebo) showed better results on complex tests and tasks, demonstrated higher indicators in concentration, task completion speed, selective attention and working memory.

The catch is that all these joys are not available in everyday life. Non-smokers are not available because they do not smoke, and there are no other sources of nicotine. Smokers are not available because they smoke and their receptors are blocked.

Nicotine only in small doses stimulates the N-cholinergic receptor. When the concentration is increased, sensitivity to it decreases up to complete blockade of the receptor, which is why nicotine is neurotoxic and can lead to death in overdose. The N-cholinergic receptor is a ligand–dependent ionotropic receptor acting as a proton channel. He is very fast and very sensitive. Quick reaction, quick desensitization, quick access to the plateau of tolerance.

Therefore, the first cigarette in the morning stands out so much: in 10-12 hours without smoking, the receptors return to their original position. All the subsequent ones have no special effect – we plant them one after the other, just to avoid withdrawal syndrome. For the same reason, unlike all other drugs, tobacco has no obvious intoxication and altered consciousness. The receptors reach a plateau much earlier than a pronounced psychoactive effect is achieved, and a further increase in the concentration of nicotine in plasma affects only the somatic component: due to the release of adrenaline and norepinephrine, small arterioles narrow (and not everywhere, for example, the vessels of the skin and brain narrow, and the vessels of skeletal muscles, on the contrary, expand), the central and peripheral pressure, pulse increases (up to threatening tachyarrhythmias and acute heart failure), the peripheral sympathetic nervous system is overexcited (due to this, nausea and vomiting develop during nicotine overdoses).

Thus, the psychostimulating, subjectively pleasant action grows only for some time, after which it is completely blocked by the increasing unpleasant manifestations of general somatic overexcitation.

Ideologically, caffeine acts in a similar way. But at the same time, caffeine acts by a different mechanism, is not directly related to the reward/punishment system, because coffee is much less likely to cause clinical dependence.

Caffeine is not a drug. And nicotine is a drug. The fact that you can't "get stoned" with cigarettes should not mislead us. This fact affects only the legal status of tobacco – you can smoke at home and at work, driving, on the street, in a restaurant and anywhere. If a Marlboro man had been demolished as a "white Chinese", he would have had the appropriate legal status. But, as you know, the receptors are not aware of the provisions of the Criminal Code of the Russian Federation.

To set dependence on a chemical substance , you need to dial three or more signs from the following seven:
1) change in tolerance and reactivity (yes);
2) withdrawal syndrome (yes);
3) regular and uncontrolled use (yes);
4) pathological attraction and / or unsuccessful attempts to stop or reduce the intake (yes);
5) most of the time, effort and money is spent on searching and using (no);
6) social maladjustment (no);
7) continued use, despite the perceived harm (is).

Thus, tobacco smoking scores five points out of seven. As already mentioned, the peculiarity of this addiction is the absence of any gingerbread and the presence of only a whip. Because there is no euphoria in use, but there is plenty of dysphoria in abstinence.

Nicotine addiction has a clear and obvious withdrawal syndrome. It is manifested by anxiety, irritability, emotional lability and affective instability, anxiety, tension, obsessive thoughts and desires, compulsive and uncontrolled attraction to nicotine, as a consequence, behavior aimed at acquiring the substance. In smokers, in a two-day separation from nicotine, the excitation of brain structures characteristic of all other drug addictions, such as cocaine and amphetamine, is recorded on f-MRI. The brain is somewhat different in alcohol and opium withdrawal, because there is a physical component in addition to the mental one (somatovegetative in alcoholics and painful in heroin addicts).

Moreover, tobacco has the highest addictive potential among all known substances. For those who occasionally use, the probability of forming an addiction within a year is more than 30% – higher than that of heroin, higher than that of cocaine, and higher than that of alcohol. Persistent three-year remission is obtained only in 5% of self-quitters and in 21% of those who quit with medical and psychological help.

Interestingly, approximately the same figures – 5% independently and 20-25% with external help – are called in different manuals for all violations related to the lack of control over impulsive behavior (not only with addictions, but also, for example, with eating disorders).

Another interesting fact. Unlike marijuana, no one is trying to pin schizophrenia on tobacco. But the vast majority of schizophrenics smoke (from 77% to 89%, according to various estimates). Apparently, in this way they are trying to smooth out the internal tension. Another explanation is that all schizophrenics take neuroleptics. All neuroleptics to a greater or lesser extent can cause unpleasant side effects associated with the blockade of acetylcholine receptors, and, apparently, nicotine somewhat facilitates the manifestations of neurolepsia.

In addition, nicotine reduces body weight. Due to the constant activation of catecholamines, it accelerates metabolism, accelerates lipolysis (destruction of adipose tissue), increases the utilization of glucose by tissues. A smoker weighs on average 4-5 kg less than a non-smoker. That when quitting smoking, weight begins to gain, this is common knowledge – everyone is aware. At the same time, due to the withdrawal syndrome, constant discomfort and the "neurotic jamming" caused by it, rarely anyone manages to limit their weight gain to only "metabolic" four kilos.

The harm of smokingThat smoking is harmful, thousands of words have been said about it.

In general, these words are true. Five to six million deaths annually around the world. One corpse every 9 seconds. In Western countries, according to the results of a long anti-smoking campaign, the number of smokers has decreased slightly, mainly among men, but in general, the figures are steadily growing across the planet. Russia is one of the most smoking countries in the world.

Smoking dramatically increases the risks of lung diseases, such as obstructive bronchitis of the smoker, emphysema of the lungs, laryngeal cancer, lung cancer. No, it's not ecology or pollution. Or rather, ecology (so in the text – VM), too, but this is an insignificant fraction. 90% of lung cancers and 95% of laryngeal cancers are tobacco. On the other hand, the incidence of lung cancer in men is 65-70 per 100 thousand per year. Russia is one of the most smoking countries on the planet, 62% of adult men smoke. That is, among these hundred thousand, about 60 thousand smoke. That means one chance in a thousand. Not to say that it was very impressive. After 60-65 years, cancer risks rise sharply and reach a peak for 70-79 years – 530 per 10,000 per year, which is already a more severe chance. But show me a man who, living in Russia, plans to pass 79 years, and we will smile approvingly at him in chorus.

At the same time, nicotine itself does not have any effect on the respiratory system at all. Bronchitis, emphysema, oncology, apnea are not nicotine, these are all the other joys that are contained in cigarette smoke. Similarly, cardiovascular diseases in smokers are products of combustion and tar. Heart attacks, strokes, atherosclerosis of blood vessels, hypertension, arrhythmias – smoking increases the risks, absolutely, undoubtedly and reliably. Obliterating endarteritis (spontaneous gangrene) in general, except in smokers, almost do not occur and are treated only by amputation of the legs.

And again, nicotine does not affect the chronic pathology of the cardiovascular system, or it affects very little. Acute, with overdoses – yes, it affects, it was mentioned above. A drop of nicotine will still kill a horse if we assume that a drop weighs 30–50mg. A lethal dose of nicotine for a person of 0.5 mg/kg is about one cigarette per kilogram of body weight. In practice, it is unrealistic to smoke three-four-five packs at the same time. A pathological condition caused by acute nicotine intoxication is an exceptionally rare case, which is usually associated not with tobacco, but with an overdose on nicotine replacement therapy – nicotine patches or electronic cigarettes.

As for chronic heart diseases, nicotine replacement therapy is allowed even after a heart attack. The cardiac risks in people who have completely given up nicotine are approximately equal to the risks in patients taking substitution therapy.

If we are to conduct anti-nicotine propaganda, then, in my opinion, it is worth pedaling more cosmetic defects caused by smoking. In smokers, the turgor (tense state of the membranes of living cells) of the skin decreases, the skin looks older, drier, acquires an unhealthy color, wrinkles appear earlier. The tooth enamel cracks and the gums are affected, tobacco resins are deposited on them, which gives the teeth a characteristic yellow color. Bad breath, from fingers, hair and clothes. Reduced taste sensitivity. A sharp decrease in the ability to distinguish odors. All these are obvious and well-known defects that any non-smoker evaluates unambiguously negatively and, at best, is ready to tolerate. At the same time, "anti-nicotine propaganda" is also not quite the right word here, because nicotine is again not guilty of all these horrors.
Let's summarize the above. Tobacco smoking by its mechanism is a completely classic drug addiction. All drug addictions have their own nuances and peculiarities, including tobacco smoking has its own specifics – this is primarily the social acceptability of drug addiction and a kind of separation of narcotic and toxic agents.

That is, smoking is practically not accompanied by objective neurotransmitter reinforcement, does not deliver significant subjective pleasure and is supported mainly by negative feedback mechanisms implemented through a pronounced withdrawal syndrome. All the troubles from tobacco are personal problems of a person, to a lesser extent – the passive smokers around him, in general, the harm to society is not very significant, which makes this addiction socially acceptable. In addition, nicotine is directly a narcotic substance, which is distinguished by the highest addiction with relatively low harmfulness to health, but at the same time with the traditional method of consumption – through inhalation of tobacco smoke, an incredible amount of various substances enters the body that do not have addictive potential at all, but have a huge harm to health.

A little about the treatmentThree drugs are used to treat nicotine addiction.

1. Bupropion. He's a wellbutrin. He's a ziban. It is not officially supplied to the Russian Federation, you can buy it from pirate smugglers. This is generally a very good, but a kind of antidepressant, a blocker of dopamine reuptake. That is, the drug acts on the same dopamine pathway as nicotine, only from the other end. Facilitates nicotine withdrawal. At the same time, as an antidepressant, it corrects mood disorders associated with withdrawal syndrome. And also promotes weight loss, treats sexual dysfunction. They can't get "stoned": some talented individuals tried – nothing good came out. It is difficult to guess why Roszdravnadzor disliked this drug.

2. Vareniklin, aka champix. Partial activator of alpha4beta2 n-cholinergic receptors (the ones that are the main suspects in the formation of addiction). It competes with nicotine for this receptor – thus, it suppresses the mechanism of nicotine reinforcement and relieves discomfort with nicotine hunger. Which of the drugs is the most effective is a philosophical question, different studies say different things. Most of the voices are in favor of vareniklin, but this is because Pfizer is a rich office and hires the best troubadours. There is also an ancient respiratory analeptic cytisine, which is sold under the name tabex as a treatment for nicotine addiction.

3. And, of course, from the troubles caused by the absence of nicotine in the body, the presence of nicotine in the body helps well, i.e. nicotine replacement therapy – nicotine patch, nicotine chewing gum, nicotine inhalers. The problem with the patch and gum is that the concentration increases slowly and smoothly, there is no nicotine peak, as when smoking. In this sense, a nicotine inhaler, known as an electronic cigarette, is much more convenient: it looks like a cigarette, there is no need to break the behavioral stereotype, the subjective sensations of good inhalers are almost identical to ordinary smoking. The difficulty is that this is a gadget, and capricious, and it needs to be dealt with and found out what's what, which not everyone has the desire for. Another problem is that electronic cigarettes were invented by the Chinese, absolutely every single device is produced by the Chinese (well, actually not all: some premium products are also produced in other countries, but this is a drop in the bucket and does not have a significant impact on the situation). Given the peculiar attitude of the Chinese to copyright, large Western offices do not show much interest in the development and implementation of these devices. Well, we should not forget that this is actually not a treatment. If the patch can still be considered as a way to facilitate quitting smoking and jump over the abyss in two jumps, then an electronic cigarette is just a way to switch from a dirty drug to a clean drug. All options make sense depending on our ultimate goals – do we want to get rid of nicotine addiction or do we want to leave addiction and remove only the collateral damage.

What else should be understood? Smoking, like all addictions, is a complex pathology. Like all addictions, this problem is not solved purely by medication. A pulmonologist will not cure you of smoking, just as a nutritionist will not cure you of obesity. Well, that is, someone, of course, will cure, and someone will be able to quit altogether. That is, in practice, everything happens: people are different, motivations are different, stenicity is also different for everyone, so I don't want to categorically assert anything. But personally, I don't see much point in purely medical intervention without psychotherapeutic interventions. Foreign doctors have detailed manuals on cognitive behavioral therapy for addicts in general and for nicotine addiction in particular.

In general, citizens have a request for help in the fight against smoking. Every single smoker knows that the Ministry of Health warns. Most of the smokers (about 70%) have tried to quit smoking or do not try, but express such a desire in words. That is, there is a request. How motivated and serious he is is another question. But he is.

List of literature:
1). Nicotine in Psychiatry: Psychopathology and Emerging Therapeutics, 2000
2). Nicotine psychopharmacology, 2009
3). Prevention of coronary heart disease: smoking, 2005
4). Nicotine and nonnicotine factors in cigarette addiction, 2006
5). The neuronal pathways mediating the behavioral and addictive properties of nicotine, 2009
6). Nicotine dependence and genetic variation in the nicotinic receptors, 2009
7). Nicotine dependence subtypes among adolescent smokers: examining the occurrence, development and validity of distinct symptom profiles, 2010
8). Tobacco habit: historical, cultural, neurobiological, and genetic features of people's relationship with an addictive drug, 2011
9). Neuronal Mechanisms Underlying Development of Nicotine Dependence: Implications for Novel Smoking-Cessation Treatments, 2011
10). Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons, 2011
11). The Dopamine Hypothesis of Drug Addiction and Its Potential Therapeutic Value, 2011
12). Impact of Genetic Variability in Nicotinic Acetylcholine Receptors on Nicotine Addiction and Smoking Cessation Treatment, 2011
13). Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction, 2012
14). Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury, 2012.

Portal "Eternal youth" http://vechnayamolodost.ru24.08.2012

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