Addiction - Causes of Development

Causes of addiction

When drug addicts are asked why they take a particular substance, most answer that they want to get a “high.” This refers to an altered state of consciousness characterized by feelings of pleasure or euphoria. The nature of the sensations experienced varies greatly depending on the type of substance used. Some people report taking drugs to relax, relieve stress, or relieve depression. It is extremely rare for a patient to take painkillers for a long time to relieve chronic headaches or back pain and then lose control of their use. However, if each case is analyzed more closely, it is impossible to give a simple answer. Almost always, several factors can be found that led to the development of addiction. These factors can be divided into three groups: those related to the substance itself, the person using it (the “host”), and external circumstances. This is similar to infectious diseases, where the possibility of a person becoming infected upon contact with the pathogen depends on several factors.

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Factors related to the nature of the psychoactive substance

Psychoactive substances vary in their ability to immediately cause pleasant sensations. When using substances that cause an intense feeling of pleasure (euphoria) more quickly, addiction is formed more easily. The formation of addiction is associated with the mechanism of positive reinforcement, due to which a person develops a desire to take the drug again and again. The stronger the ability of a drug to activate the mechanism of positive reinforcement, the higher the risk of abuse. The ability of a drug to activate the mechanism of positive reinforcement can be assessed using an experimental model. For this, laboratory animals are given intravenous catheters through which the substance should be administered. The catheters are connected to an electric pump, the operation of which the animals can regulate using a special lever. As a rule, animals such as rats and monkeys seek a more intensive introduction of those drugs that cause addiction in humans, and the ratio of their activity is approximately the same. Thus, using such an experimental model, it is possible to assess the ability of a drug to cause addiction.

The reinforcing properties of drugs are related to their ability to increase dopamine levels in certain areas of the brain, especially in the nucleus accumbens (NA). Cocaine, amphetamine, ethanol, opioids, and nicotine can increase extracellular dopamine levels in the NA. Microdialysis can be used to measure dopamine levels in the extracellular fluid of rats that are freely moving or taking drugs. It turned out that both the receipt of sweet food and the opportunity to have sexual intercourse resulted in a similar increase in dopamine levels in brain structures. In contrast, drugs that block dopamine receptors tend to cause unpleasant sensations (dysphoria); neither animals nor people voluntarily take these drugs repeatedly. Although the cause-and-effect relationship between dopamine levels and euphoria or dysphoria has not been definitively established, such a connection is supported by the results of studies of drugs of different classes.

Multiple independent factors influencing the initiation and continuation of substance use, abuse and dependence

"Agent" (psychoactive substance)

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

"The Host" (the person using the psychoactive substance)

• Heredity
• Innate tolerance
• Rate of development of acquired tolerance
• The probability of experiencing intoxication as pleasure
• Mental symptoms
• Prior experience and expectations
• Tendency to engage in risky behavior

Wednesday

• Social conditions
• Relationships in social groups Peer influence, role models
• Availability of other ways to enjoy or have fun
• Job and Education Opportunities
• Conditioned stimuli: external factors become associated with drug use after repeated use in the same environment

Substances with a rapid onset of action are more likely to cause addiction. The effect that occurs soon after taking such a substance is likely to initiate a sequence of processes that eventually lead to a loss of control over the use of the substance. The time it takes for the substance to reach receptors in the brain and its concentration depend on the route of administration, the rate of absorption, the characteristics of metabolism, and the ability to penetrate the blood-brain barrier. The history of cocaine clearly demonstrates how the ability of the same substance to cause addiction can change with a change in its form and route of administration. The use of this substance began with chewing coca leaves. This releases the alkaloid cocaine, which is slowly absorbed through the mucous membrane of the oral cavity. As a result, the concentration of cocaine in the brain increases very slowly. Therefore, the mild psychostimulant effect of chewing coca leaves appeared gradually. At the same time, over several thousand years of use of coca leaves by Andean Indians, cases of addiction, if observed, were extremely rare. At the end of the 19th century, chemists learned to extract cocaine from coca leaves. Thus, pure cocaine became available. It became possible to take cocaine in high doses orally (where it was absorbed in the gastrointestinal tract) or snort the powder into the nose so that it was absorbed by the nasal mucosa. In the latter case, the drug acted faster, and its concentration in the brain was higher. Subsequently, a solution of cocaine hydrochloride began to be administered intravenously, which caused a more rapid development of the effect. With each such advance, higher levels of cocaine were achieved in the brain, and the speed of onset of action increased, and along with this, the ability of the substance to cause addiction increased. Another "achievement" in the methods of cocaine administration occurred in the 1980s and was associated with the emergence of so-called "crack". Crack, which could be bought very cheaply right on the street (for $ 1-3 per dose), contained an alkaloid of cocaine (free base), which easily evaporated when heated. Inhaling crack vapor produced the same blood concentrations of cocaine as injecting it intravenously. The pulmonary route is particularly effective because of its large surface area for absorption of the drug into the blood. Blood with a high cocaine content returns to the left side of the heart and from there enters the systemic circulation without being diluted by venous blood from other parts. Thus, a higher concentration of the drug is created in arterial blood than in venous blood. Due to this, the drug reaches the brain faster. This is the preferred route of administration of cocaine by nicotine and marijuana abusers. Thus, inhaling crack vapor will cause addiction faster than chewing coca leaves, ingesting cocaine, or snorting cocaine powder.

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

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Factors associated with the user of the substance ("host")

The sensitivity of people to psychoactive substances varies considerably. When the same dose of a substance is administered to different people, its concentration in the blood is not the same. These variations are at least partly explained by genetically determined differences in the absorption, metabolism, and excretion of the substance, as well as in the sensitivity of the receptors on which it acts. One result of these differences is that the effect of the substance may also be subjectively felt differently. In people, it is very difficult to separate the influence of heredity from the influence of the environment. The ability to assess the influence of these factors separately is provided by studies of children who were adopted early and had no contact with their biological parents. It has been noted that the biological children of alcoholics are more likely to develop alcoholism even if they were adopted by people who do not have an addiction to alcohol. However, research into the role of hereditary factors in this disease shows that the risk of developing alcoholism in children of alcoholics is increased, but 100% predetermined. These data indicate that this is a polygenic (multifactorial) disease, the development of which depends on many factors. When studying identical twins with the same set of genes, the concordance rate for alcoholism does not reach 100%, but it is significantly higher than in fraternal twins. One of the biological indicators influencing the development of alcoholism is innate tolerance to alcohol. Studies show that sons of alcoholics have a reduced sensitivity to alcohol compared to young people of the same age (22 years) with similar experience of drinking alcoholic beverages. Sensitivity to alcohol was assessed by studying the effect of two different doses of alcohol on motor functions and by the subjective feeling of intoxication. When these men were re-examined 10 years later, it turned out that those who were more tolerant (less sensitive) to alcohol at age 22 were more likely to develop alcohol dependence later. Although tolerance increased the likelihood of developing alcoholism regardless of family history, the proportion of tolerant individuals was higher among people with a positive family history. Of course, innate tolerance to alcohol does not make a person an alcoholic, but it significantly increases the likelihood of developing this disease.

Research shows that the opposite quality - resistance to alcoholism - can also be hereditary. Ethanol is converted into acetaldehyde with the help of alcohol dehydrogenase, which is then metabolized by mitochondrial aldehyde acetaldehyde (ADCH2). A mutation in the ADCH2 gene is common, which can make the enzyme less effective. This mutant allele is especially common among Asians and leads to the accumulation of acetaldehyde, a toxic product of alcohol. Carriers of this allele experience an extremely unpleasant rush of blood to the face 5-10 minutes after drinking alcohol. The likelihood of developing alcoholism in this category of people is lower, but its risk is not completely eliminated. There are people with a strong motivation to drink alcohol, who stoically endure the feeling of a rush in order to experience other effects of alcohol - they can become alcoholics. Thus, the development of alcoholism depends not on one gene, but on many genetic factors. For example, people with inherited tolerance to alcohol and therefore prone to developing alcoholism may refuse to drink alcohol. Conversely, people who experience a rush from alcohol may continue to abuse it.

Mental disorders are another important factor in the development of addiction. Some drugs provide immediate subjective relief of mental symptoms. Patients with anxiety, depression, insomnia, or certain psychological characteristics (such as shyness) may accidentally discover that certain substances provide relief. However, this improvement is temporary. With repeated use, they develop tolerance, and over time, compulsive, uncontrolled drug use. Self-medication is one way people fall into this trap. However, the proportion of addicts who ever self-medicated remains unknown. Although mental disorders are often found in substance abusers who seek treatment, many of these symptoms develop after the person has begun to abuse the substance. In general, addictive substances produce more mental disorders than they relieve.

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External factors

The onset and continuation of illegal drug use is greatly influenced by social norms and parental pressure. Sometimes adolescents use drugs as a form of rebellion against the authority of their parents or caregivers. In some communities, drug users and drug dealers are role models who are respected and attractive to young people. Lack of access to other entertainment and pleasure opportunities may also be important. These factors are especially important in communities with low educational levels and high unemployment. Of course, these are not the only factors, but they potentiate the influence of the other factors described in the previous sections.

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Pharmacological phenomena

Although abuse and dependence are extremely complex conditions whose manifestations depend on many circumstances, they are characterized by a number of common pharmacological phenomena that occur independently of social and psychological factors. First, they are characterized by a change in the body's response to repeated administration of a substance. Tolerance is the most common type of change in response to repeated administration of the same substance. It can be defined as a decrease in the response to a substance when it is administered again. With sufficiently sensitive methods for assessing the action of a substance, the development of tolerance to some of its effects can be observed after the first dose. Thus, a second dose, even if administered only a few days later, will have a slightly lesser effect than the first. Over time, tolerance can develop even to high doses of a substance. For example, in a person who has never used diazepam before, this drug usually causes a sedative effect at a dose of 5-10 mg. But those who have used it repeatedly to get a particular type of "high" may develop tolerance to doses of several hundred milligrams, and in some documented cases tolerance has been noted to doses exceeding 1000 mg per day.

Tolerance to some effects of psychoactive substances develops more quickly than to others. For example, when opioids (such as heroin) are administered, tolerance to euphoria develops quickly, and addicts are forced to increase the dose in order to “catch” this elusive “high.” In contrast, tolerance to the effects of opioids on the intestines (weakening of motility, constipation) develops very slowly. Dissociation between tolerance to the euphorogenic effect and the effect on vital functions (such as breathing or blood pressure) can cause tragic consequences, including death. Abuse of sedatives such as barbiturates or methaqualone is quite common among adolescents. With repeated administration, they need to take increasingly higher doses in order to experience the state of intoxication and drowsiness that they perceive as a “high.” Unfortunately, tolerance to this effect of sedatives develops faster than tolerance to the effects of these substances on vital brainstem functions. This means that the therapeutic index (the ratio of the dose that causes a toxic effect to the dose that causes a desired effect) decreases. Since the previous dose no longer produces a feeling of "high," these young people increase the dose beyond the safe range. And when they increase it again, they may reach a dose that suppresses vital functions, leading to a sudden drop in blood pressure or respiratory depression. The result of such an overdose can be fatal.

"Iatrogenic addiction." This term is used when patients develop an addiction to a prescribed drug and begin to take it in excessive doses. This situation is relatively rare, given the large number of patients who take 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, patients may, without the physician's knowledge, seek other doctors and emergency medical services in the hope of receiving additional amounts of the drug. Because of fears of addiction, many doctors unnecessarily limit the prescription of certain drugs, thereby condemning patients, for example, those 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 by themselves do not necessarily mean the development of addiction.

Addiction as a brain disease

Chronic administration of addictive substances results in persistent changes in behavior that are involuntary, conditioned reflexes, and persist for a long time, even with complete abstinence. These conditioned reflexes or psychoactive substance-induced memory traces may play a role in the development of relapses to compulsive drug use. Wickler (1973) was the first to draw attention to the role of the conditioned reflex in the development of addiction. A number of studies have examined neurochemical changes, as well as changes at the level of gene transcription, associated with long-term administration of psychoactive substances. The results of these studies not only deepen our understanding of the nature of addiction, but also open up new possibilities for its treatment and the development of therapeutic approaches similar to those used in other chronic diseases.

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The socio-economic costs of substance abuse

Currently, the most important clinical problems in the United States are caused by four substances - nicotine, ethyl alcohol, cocaine and heroin. In the United States alone, 450,000 people die each year from nicotine contained in tobacco smoke. According to some estimates, up to 50,000 non-smokers also die each year from passive exposure to tobacco smoke. Thus, nicotine is the most serious public health problem. In one year, alcoholism inflicts economic losses on society of 100 billion dollars and takes the lives of 100,000 people in the United States, of whom 25,000 die in traffic accidents. Illegal drugs such as heroin and cocaine, although their use is often associated with HIV infection and crime, are less often the cause of 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 spends approximately $140 billion annually on the War on Drugs program, with approximately 70% of that amount going toward various legal measures (such as combating drug trafficking).

Addicts often prefer one of these substances, based, among other things, on its availability. But they often resort to a combination of drugs from different groups. Alcohol is a common substance that is combined with almost all other groups of psychoactive substances. Some combinations deserve special mention due to the synergistic effect of the combined substances. An example is a combination of heroin and cocaine (the so-called "speedball"), which is discussed in the section on opioid addiction. When examining a patient with signs of overdose or withdrawal syndrome, the physician should consider the possibility of a combination, since each of the drugs may require specific therapy. About 80% of alcoholics and an even higher percentage of heroin users are also smokers. In these cases, treatment should be aimed at both types of addiction. The clinician should primarily treat the most pressing problem, which is usually alcohol, heroin, or cocaine addiction. However, when conducting a course of treatment, attention should also be paid to the correction of concomitant nicotine addiction. Serious nicotine addiction cannot be ignored just because the main problem is alcohol or heroin abuse.