Addiction: causes of development

Causes of dependence

When drug addicts are asked why they take this or that substance, most respond that they want to get a "buzz". By this means an altered state of consciousness characterized by sensations of pleasure or euphoria. The nature of the sensations obtained varies considerably depending on the type of substances used. Some people report that they are taking drugs in order to relax, get rid of stress or depression. Very rarely there is a situation where the patient takes analgesics for a long time to get rid of chronic headache or back pain, and then loses control over their use. Nevertheless, if each case is analyzed more carefully, then one simple answer is impossible. Almost always you can find several reasons that led to the formation of dependence. These factors can be divided into three groups: related to the substance itself, the person consuming it (the "master"), and external circumstances. It resembles infectious diseases, when the possibility of infection of a person in contact with the pathogen depends on several factors.

[1], [2], [3], [4]

Factors related to the nature of the psychoactive substance

Psychoactive substances differ in their ability to immediately evoke pleasant sensations. With the use of substances that quickly cause an intense sense of pleasure (euphoria), dependence is formed more easily. Formation of dependence is associated with the mechanism of positive reinforcement, due to which a person has an urge to take the drug again and again. The stronger the ability of the drug to activate the mechanism of positive reinforcement, the higher the risk of abuse. The ability of the drug to activate the mechanism of positive reinforcement can be assessed on an experimental model. To this end, laboratory animals are provided with intravenous catheters through which the substance must enter. The catheters are connected to an electric pump, the work of which the animals can regulate through a special lever. As a rule, animals such as rats and monkeys tend to more intensively administer those drugs that cause dependence in humans, and the ratio of their activity is approximately the same. Thus, with the help of such an experimental model, the ability of the drug to induce dependence can be assessed.

The reinforcing properties of drugs are associated with their ability to raise the level of dopamine in certain areas of the brain, especially in the nucleus accumbens (AE). Cocaine, amphetamine, ethanol, opioids and nicotine are able to increase the level of extracellular dopamine in the PO. Using microdialysis, it is possible to measure the level of dopamine in extracellular fluid in rats that move freely or take narcotic drugs. It turned out that both in obtaining sweet food, and at the opportunity to perform sexual intercourse in the brain structures, there was a similar increase in the content of dopamine. On the contrary, drugs that block dopamine receptors tend to cause unpleasant sensations (dysphoria); neither animals nor people independently take these drugs repeatedly. Although the causal relationship between the level of dopamine and euphoria or dysphoria is not completely established, the results of studies of drugs of various classes testify to this relationship.

Multiple independent factors that influence the onset and continuation of the use of psychoactive substances, the development of abuse and dependence

"Agent" (psychoactive substance)

• Availability
• Price
• Degree of purification and activity
• The route of administration
• Chewing (absorption through the mucosa of the oral cavity) Ingestion (absorption in the gastrointestinal tract) Intranasal
• Parenteral (intravenous subcutaneous or intramuscular) Inhalation
• The rate of onset and termination of the effect (pharmacokinetics) is determined simultaneously by the nature of the substance and the features of human metabolism

"Boss" (a person who uses a psychoactive substance)

• Heredity
• Congenital tolerance
• The rate of development of acquired tolerance
• Probability of experiencing intoxication as pleasure
• Mental symptoms
• Prior experience and expectations
• Inclination to risk behavior

Wednesday

• Social conditions
• Relationships in social groups Peer influence, role models
• Accessibility of other ways of obtaining pleasure or entertainment
• Opportunities for work and education
• Conditionally reflex stimuli: external factors are associated with taking the drug after it is re-used in the same environment

Substances with a fast action often cause dependence. The effect that occurs soon after taking such a substance is likely capable of initiating a sequence of processes that ultimately lead to a loss of control over the use of the substance. The time for which the substance reaches the receptors in the brain and its concentration depend on the route of administration, the rate of absorption, the metabolic features and the ability to penetrate the blood-brain barrier. The history of cocaine clearly demonstrates how the ability of the same substance to change can cause dependence when changing its shape and route of administration. The use of this substance began with the chewing of coca leaves. In this case, alkaloid is released cocaine, which is slowly absorbed through the oral mucosa. As a result, the concentration of cocaine in the brain rises very slowly. Therefore, a light psycho-stimulating effect on the chewing of coca leaves was manifested gradually. In this case, for several thousand years, the use of coca leaves by Andean Indians, cases of dependence, if observed, are extremely rare. At the end of the XIX century, chemists learned to extract cocaine from coca leaves. Thus, pure cocaine became available. There was an opportunity to take cocaine in high doses inside (while it was absorbed in the gastrointestinal tract) or inhale the powder in the nose so that it absorbed the nasal mucosa. In the latter case, the drug acted faster, and its concentration in the brain was higher. Subsequently, the solution of cocaine hydrochloride was injected intravenously, which caused a more rapid development of the effect. With each such advancement, an increasingly high level of cocaine in the brain was achieved, and the rate of onset of action increased, and with it the ability of the substance to increase dependence also increased. Another "achievement" in the methods of cocaine introduction occurred in the 1980s and was associated with the appearance of the so-called "crack". Crack, which could be very cheap to buy directly on the street (for $ 1-3 per dose), contained a cocaine alkaloid (free base) that evaporated easily when heated. When inhaling the crack cracker, the same level of cocaine concentration in the blood as in its intravenous administration was achieved. The pulmonary route of administration is particularly effective because of the large surface area for absorption of the drug into the blood. Blood with a high content of cocaine returns to the left heart and from there gets into a large circle of blood circulation without diluting venous blood from other departments. Thus, a higher concentration of the drug is created in the arterial blood than in the venous blood. Due to this, the drug quickly enters the brain. It is this way of introducing cocaine that people who abuse nicotine and marijuana prefer. Thus, the inhalation of crack vapors will more quickly cause dependence than chewing coca leaves, consuming cocaine inside, or inhaling cocaine powder.

Although the characteristics of the substance are very important, they can not fully explain why abuse and dependence develop. Most people who try the drug do not use it repeatedly and do not become addicts. "Experiments" even with substances that have a strong reinforcing effect (for example, cocaine) lead to the development of dependence in only a small number of cases. The development of dependence, therefore, depends on two other groups of factors-the characteristics of the person who uses the drug and the circumstances of his life.

[5], [6], [7],

Factors associated with the consumer of the substance (the "master")

The sensitivity of people to psychoactive substances varies significantly. When different people are given the same dose of substance, its concentration in the blood is not the same. These variations are at least partially explained by genetically determined differences in absorption, metabolism and excretion of the substance, as well as in the sensitivity of the receptors to which it affects. One of the results of these differences is that the effect of the substance can also be felt subjectively differently. It is very difficult for people to separate the influence of heredity from the influence of the environment. The ability to assess the impact of these factors individually gives research to children who were early confined and had no contact with biological parents. It is noted that in the case of biological children of alcoholics, the likelihood of developing alcoholism is higher even if they were adopted by people who are not addicted to alcohol. However, the study of the role of hereditary factors in this disease shows that in children of alcoholics the risk of alcoholism is elevated, but is 100% predetermined. These data indicate that this is a polygenic (multifactorial) disease, the development of which depends on many factors. In the study of identical twins having the same set of genes, the degree of concordance for alcoholism does not reach 100%, however, it is significantly higher than in the case of fraternal twins. One of the biological indicators that affect the development of alcoholism is congenital tolerance to alcohol. Studies show that the sons of alcoholics have a reduced sensitivity to alcohol compared to young people of the same age (22 years) who have a similar experience of drinking alcoholic beverages. The sensitivity to alcohol was assessed by examining the effect of two different doses of alcohol on motor functions and the subjective feeling of intoxication. At a repeated examination of these men after 10 years, it turned out that the comfort, who was more tolerant (less sensitive) to alcohol at the age of 22, later often developed alcohol dependence. Although the presence of tolerance increased the likelihood of alcoholism regardless of family history, among people with a positive family history the proportion of tolerant individuals was higher. Of course, congenital tolerance to alcohol does not yet make a person an alcoholic, but it significantly increases the likelihood of developing this disease.

Studies show that the opposite quality - resistance to alcoholism development - can also be hereditary. Ethanol with alcohol dehydrogenase is converted to acetaldehyde, which is then metabolized by mitochondrial aldehyde hydrogenase (ADCG2). There is often a mutation in the gene ADGG2, because of which the enzyme may be less effective. This mutant allele is especially prevalent among the population of Asia and leads to the accumulation of acetaldehyde, a toxic product of alcohol. In carriers of this allele, a very unpleasant rush of blood to the face occurs after 5-10 minutes after drinking alcohol. The likelihood of developing alcoholism in this category of people is less, but its risk is not completely eliminated. There are people with strong motivation to drink alcohol, which stoically tolerate the sensation of the tide for the sake of experiencing other effects of alcohol - they can become alcoholics. Thus, the development of alcoholism does not depend on one gene, but on a variety of genetic factors. For example, people with inherited tolerance to alcohol and because of this inclined to the development of alcoholism may refuse to drink alcohol. Conversely, people who have alcohol causing a tide can continue to abuse it.

Psychiatric disorders are another important factor affecting the development of addiction. Some drugs cause immediate subjective relief of mental symptoms. Patients with anxiety, depression, insomnia or some psychological features (eg, shyness) may inadvertently find that some substances bring them relief. However, this improvement proves to be temporary. With repeated use, they develop tolerance, and over time - compulsive, uncontrolled use of drugs. Self-medication is one of the ways of getting people into such a trap. However, the proportion of drug addicts who once started with self-treatment remains unknown. Although mental disorders are often detected in people who abuse psychoactive substances who seek treatment, many of these symptoms develop after the person has started to abuse them. In general, addictive substances produce more psychiatric disorders than they facilitate.

[8], [9], [10], [11],

External factors

The beginning and continuation of the use of illegal psychoactive substances largely depends on the influence of social norms and the pressure of parents. Sometimes adolescents take drugs as a protest against the power of parents or educators. In some communities, drug addicts and drug distributors are role models that are respected and attractive to young people. Another important factor is the inaccessibility of other entertainments and opportunities for enjoyment. These factors are especially important in communities with a low educational level and high unemployment. Of course, these factors are not unique, but they potentiate the influence of other factors described in the previous sections.

[12], [13], [14],

Pharmacological phenomena

Although abuse and dependence are extremely complex states, the manifestations of which depend on many circumstances, they are characterized by a number of common pharmacological phenomena that arise independently of social and psychological factors. First, they are characterized by a change in the body's response to the repeated administration of the substance. Tolerance is the most frequent variant of changing the reaction with the repeated administration of the same substance. It can be defined as a decrease in the reaction to a substance when it is reintroduced. With the use of sufficiently sensitive methods for evaluating the effect of a substance, the development of tolerance to some of its effects can be seen after the first dose. Thus, the second dose, even if administered only after a few days, will cause a slightly smaller effect than the first. Over time, tolerance can develop even to high doses of the substance. For example, in a person who has never previously used diazepam, this drug usually causes a sedative effect in a dose of 5-10 mg. But those who took it repeatedly to get a certain kind of "buzz" can develop tolerance to doses of several hundred milligrams, and in some documented cases tolerance to doses exceeding 1000 mg per day is noted.

To some effects of psychoactive substances, tolerance occurs faster than other effects. So, with the introduction of opioids (for example, heroin), tolerance for euphoria is rapidly developing, and drug addicts are forced to increase the dose in order to "catch" this elusive "buzz". On the contrary, tolerance to the action of opioids on the intestines (weakening of motor function, constipation) develops very slowly. The dissociation between tolerance to euphorogenous action and action on vital functions (for example, respiration or blood pressure) can be the cause of tragic consequences, including death. Among adolescents, abuse of sedatives, such as barbiturates or methaqualone, is quite common. When reintroduced, in order to experience the state of intoxication and drowsiness, which they perceive as "kicks," they need to take ever higher doses. Unfortunately, the tolerance to this action of sedatives is developing more rapidly than to the action of these substances on vital stem functions. This means that the therapeutic index (the ratio of the dose causing the toxic effect and the dose causing the desired effect) is reduced. Since the dose previously taken no longer causes a sense of "buzz", these young people increase the dose beyond the safe range. And with the next increase, they can reach a dose that suppresses vital functions, which will lead to a sudden drop in blood pressure or respiratory depression. As a result of such an overdose, a fatal outcome may occur.

"Iatrogenic addiction." This term is used in those situations when patients develop a predilection for the drug prescribed to them, and they start using it in an excessive dose. This situation is relatively rare, given the large number of patients taking drugs that can cause tolerance and physical dependence. An example is patients with chronic pain who take the drug more often than prescribed by the doctor. If the attending physician prescribes a limited amount of the drug, the patients can consult other doctors, as well as the emergency services, without his knowledge, in the hope of obtaining an additional amount of the drug. Because of fears before the development of addiction, many doctors unreasonably restrict the discharge of certain drugs and thereby doom patients, for example, suffering from pain syndromes, to unnecessary suffering. The development of tolerance and physical dependence is an inevitable consequence of chronic treatment with opioids and some other drugs, but tolerance and physical dependence in themselves do not mean the development of addiction.

Dependence as a disease of the brain

The constant introduction of addictive substances leads to persistent changes in behavior that have an involuntary conditioned reflex character and persist for a long time, even with complete abstinence. These conditioned reflex reactions or psychoactive substance induced memory traces can play a role in the development of recurrences of compulsive drug use. Wickler (1973) was the first to draw attention to the role of the conditioned reflex in the formation of dependence. A number of studies have studied neurochemical changes, as well as changes in the level of transcription of genes associated with long-term administration of psychoactive substances. The results of these studies not only deepen the understanding of the nature of dependence, but also open new opportunities for its treatment and the development of therapeutic approaches similar to those used for other chronic diseases.

[15], [16], [17]

Socio-economic damage to substance abuse

Currently, in the United States, the most important clinical problems are caused by four substances - nicotine, ethyl alcohol, cocaine and heroin. Only in the US, from the nicotine contained in tobacco smoke, 450,000 people die each year. According to some reports, up to 50,000 non-smoking persons who are passively exposed to tobacco smoke also die in a year. Thus, nicotine is the most serious public health problem. In one year in the US, alcoholism inflicts economic damage on society at 100 billion dollars and takes the lives of 100,000 people, of whom 25,000 perish in road accidents. Illegal drugs, such as heroin and cocaine, although their use is often associated with HIV infection and crime, are less likely to cause death - they account for 20,000 cases per year. Nevertheless, the economic and social damage caused by the use of illegal drugs is enormous. The US government annually allocates approximately $ 140 billion for the "War on Drugs" program, with approximately 70% of this amount going to various legal measures (for example, to combat their proliferation).

Addicts often prefer one of these substances, focusing, among other things, on its availability. But often they resort to a combination of drugs from different groups. Alcohol is a widespread substance that is combined with virtually all other groups of psychoactive substances. Some combinations deserve special mention because of the synergism of the action of the combined substances. An example could be a combination of heroin and cocaine (the so-called "speedball"), which is discussed in the section on opioid dependence. When examining a patient with signs of overdose or withdrawal symptoms, the doctor should consider the possibility of a combination, as each of the drugs may require specific therapy. Approximately 80% of alcoholics and even an even higher percentage of those who use heroin are also smokers. In these cases, treatment should be directed to both types of dependence. The clinician should first of all carry out medical measures on the most urgent problem, which is usually alcoholic, heroin or cocaine addiction. Nevertheless, in the course of treatment, attention should be paid to the correction of concomitant nicotine addiction. One can not ignore the serious dependence on nicotine just because the main problem is the abuse of alcohol or heroin.