Alcoholism

Alcoholism, or alcohol dependence, is a chronic excessive consumption consisting of compulsive drinking, growing tolerance, and withdrawal symptoms.

Excessive alcohol consumption can lead to severe physical and mental problems.

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Epidemiology

About two-thirds of American adults drink alcohol. The male to female ratio is 4:1. The combined lifetime prevalence of alcohol abuse and alcoholism is about 15%.

People who abuse alcohol and are dependent on it usually have serious social problems. Frequent intoxication is obvious and destructive, it interferes with the ability to socialize and work. Thus, drunkenness and alcoholism can lead to the destruction of social relationships, loss of work due to absenteeism. In addition, due to drunkenness, a person can be subject to arrest, detention for drunk driving, which aggravates the social consequences of alcohol use. In the USA, the legal blood alcohol concentration for driving in most states is £ 80 mg/dl (0.08%).

Women with alcoholism tend to drink alone more often and are less socially stigmatized. Patients who have alcoholism may seek medical help for their drinking. They may end up hospitalized with delirium tremens or cirrhosis of the liver. They often suffer injuries. The earlier in life the behavior becomes evident, the more severe the disorder.

The incidence of alcoholism is higher in biological children of alcoholic parents than in adopted children, and the percentage of children of alcoholic parents who have alcohol problems is higher than in the general population. Accordingly, the prevalence of alcoholism is higher in some populations and countries. There is evidence of a genetic or biochemical predisposition, including evidence that some people who became alcoholics developed intoxication more slowly, i.e., they had a higher threshold for the effects of alcohol on the central nervous system.

You can read in detail about the prevalence and statistics of alcoholism in different countries of the world here.

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Causes alcoholism

Alcoholism is a disease so ancient that even the date of 8000 BC, when the alcoholic drink was first mentioned, is not exact. Judging by the scale of alcoholism, it seems that this disease has been in the blood of almost half the world's population since the time of Adam and Eve. We are not talking about the culture of drinking, this is a separate topic for discussion. The problem is that this culture is disappearing, and total alcoholism is moving in its place at a rapid pace. Judge for yourself: according to UN standards, drinking more than nine liters of alcoholic beverages per year is considered a disease. How many people adhere to these standards? Alcoholism develops unnoticed, and when it reaches a threatening stage, such a persistent addiction is formed that it is certainly possible to cure it, but it is extremely difficult and requires a long period. The problem is that the person addicted to alcohol stubbornly does not admit his illness, mainly close people sound the alarm. This may explain the low percentage of recovery from alcohol addiction – after all, most often the patient is simply forced to see a doctor, and his personal motivation in this process almost always tends to zero.

Alcohol abuse is generally defined as uncontrolled drinking that results in failure to meet obligations, exposure to dangerous situations, legal problems, social and interpersonal difficulties, and no evidence of addiction.

Alcoholism is defined as the frequent consumption of large quantities of alcohol, leading to tolerance, psychological and physical dependence, and dangerous withdrawal symptoms. The term alcoholism is often used synonymously with alcohol dependence, especially when alcohol consumption results in clinically significant toxic effects and tissue damage.

Drinking alcohol to the point of intoxication or developing maladaptive drinking patterns that lead to abuse begins with the desire to achieve pleasurable sensations. Some who drink alcohol and enjoy it then seek to repeat this state periodically.

Those who regularly drink alcohol or become dependent on it have some personality traits that are more pronounced: isolation, loneliness, shyness, depression, dependency, hostility and self-destructive impulsivity, sexual immaturity. Alcoholism often comes from broken families, these alcoholics have a broken relationship with their parents. Social factors transmitted through culture and upbringing influence the characteristics of alcohol consumption and subsequent behavior.

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Pathogenesis

Alcohol is a CNS depressant, producing a sedative effect and causing drowsiness. However, the initial effect of alcohol, especially in low doses, is often stimulating, probably due to the suppression of inhibitory systems. Volunteers who experienced only a sedative effect after drinking alcohol did not return to it in a free choice situation. More recently, it has been shown that alcohol enhances the action of the inhibitory mediator gamma-aminobutyric acid (GABA) on a certain subpopulation of GABA receptors. In addition, ethanol can increase the activity of dopaminergic neurons in the ventral tegmentum projecting to the nucleus accumbens, which leads to an increase in the level of extracellular dopamine in the ventral striatum. This activation may be mediated through GABA receptors and the suppression of inhibitory interneurons. It has been shown that this effect is reinforced as rats are trained to receive alcohol. Moreover, the level of dopamine in the nucleus accumbens increases as soon as the rats are placed in a cage where they previously received alcohol. Thus, one of the pharmacological effects of alcohol - an increase in the level of extracellular dopamine in the nucleus accumbens - is similar to the effect of other addictive substances - cocaine, heroin, nicotine.

There is also evidence of the involvement of the endogenous opioid system in the reinforcing effect of alcohol. A series of experiments showed that animals trained to receive alcohol cease to perform the actions necessary for this after the introduction of the opioid receptor antagonists naloxone or naltrexone. These data are consistent with the results recently obtained in a study of alcoholics - against the background of the introduction of the long-acting opioid receptor antagonist naltrexone, the feeling of euphoria when taking alcohol is weakened. Alcohol intake in the laboratory causes a significant increase in the level of peripheral beta-endorphin only in volunteers with a family history of alcoholism. There is also evidence of the involvement of the serotonergic system in providing the reinforcing effect of alcohol. It is possible that alcohol, which reaches the central nervous system in a relatively high concentration and affects the fluidity of the cell membrane, is able to affect several neurotransmitter systems. Accordingly, there may be several mechanisms for the development of euphoria and addiction.

Alcohol impairs memory for recent events and, in high concentrations, causes “blackouts” in which circumstances and actions during the period of intoxication are lost from memory. The mechanism by which it affects memory is unclear, but experience shows that patients’ reports of the reasons for drinking alcohol and their actions while intoxicated do not correspond to reality. Alcoholics often claim that they drink to relieve anxiety and depression. However, observations show that they usually become increasingly dysphoric as the dose they drink increases, which contradicts the explanation given above.

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Symptoms alcoholism

Alcoholism is considered a serious disease, with a chronic, long-term course, which begins covertly, asymptomatically, and can end very sadly.

Signs of acute alcohol intoxication

Alcohol is absorbed into the blood mainly from the small intestine. It accumulates in the blood, since absorption occurs faster than oxidation and elimination. From 5 to 10% of consumed alcohol is excreted unchanged in urine, sweat, exhaled air; the rest is oxidized to CO2 _and water at a rate of 5-10 ml/h of absolute alcohol; each milliliter gives about 7 kcal. Alcohol is mainly a CNS depressant.

Blood alcohol concentrations of about 50 mg/dL cause sedation or tranquility; concentrations of 50 to 150 mg/dL cause incoordination; 150 to 200 mg/dL cause delirium; and concentrations of 300 to 400 mg/dL cause loss of consciousness. Concentrations greater than 400 mg/dL can be fatal. Sudden death due to respiratory depression or arrhythmia can occur when large amounts of alcohol are consumed rapidly. These problems arise in colleges in the United States, but also in other countries where the syndrome is more common.

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Signs of chronic alcoholism

Patients who frequently consume large amounts of alcohol become tolerant to its effects, i.e., the same amount of the substance eventually produces less intoxication. Tolerance is caused by adaptive changes in the cells of the central nervous system (cellular or pharmacodynamic tolerance). Patients who have developed tolerance may have unrealistically high blood alcohol concentrations. On the other hand, tolerance to alcohol is incomplete, and some degree of intoxication and damage occurs at sufficiently high doses. Even highly tolerant patients may die from respiratory depression secondary to alcohol overdose. Patients who have developed tolerance are susceptible to alcoholic ketoacidosis, especially during binge drinking. Patients develop cross-tolerance to many other central nervous system depressants (e.g., barbiturates, sedatives of other structures, benzodiazepines).

The physical dependence that accompanies tolerance is severe, and potentially fatal adverse effects may develop during withdrawal. Alcoholism eventually leads to organ damage, most commonly hepatitis and cirrhosis, gastritis, pancreatitis, cardiomyopathy often accompanied by arrhythmias, peripheral neuropathy, brain damage [including Wernicke's encephalopathy, Korsakoff's psychosis, Marchiafava-Bignami disease, and alcoholic dementia].

Signs and symptoms of alcohol withdrawal usually appear 12 to 48 hours after stopping drinking. Mild withdrawal symptoms include tremors, weakness, sweating, hyperreflexia, and gastrointestinal symptoms. Some patients develop tonic-clonic seizures, but usually no more than 2 seizures in a row (alcoholic epilepsy).

Symptoms of alcohol addiction

Almost everyone has experienced mild alcohol intoxication, but its manifestations are extremely individual. Some people only experience impaired coordination and drowsiness. Others become excited and talkative. As the concentration of alcohol in the blood increases, the sedative effect increases, leading to coma. At very high concentrations of alcohol, death occurs. Initial sensitivity (innate tolerance) to alcohol varies significantly and correlates with the presence of alcoholism in the family history. A person with low sensitivity to alcohol can tolerate large doses even at first use, without experiencing impaired coordination or other symptoms of intoxication. As already noted, such people are predisposed to the subsequent development of alcoholism. With repeated use, tolerance can gradually increase (acquired tolerance), so even with a high level of alcohol in the blood (300-400 mg / dl), alcoholics do not look drunk. However, the lethal dose does not increase proportionally to tolerance to the sedative effect, and thus the safe dose range (therapeutic index) narrows.

Binge drinking not only develops tolerance, but inevitably leads to physical dependence. The person is forced to drink in the morning to restore the blood alcohol level, which has dropped due to the fact that a significant portion of the alcohol has been metabolized overnight. Over time, such individuals may wake up in the middle of the night and drink to avoid the anxiety caused by low alcohol levels. Alcohol withdrawal syndrome usually depends on the average daily dose and is usually relieved by the introduction of alcohol. Withdrawal symptoms are common, but they are usually not severe or life-threatening in themselves, unless other problems are present, such as infection, injury, nutritional or electrolyte imbalance. In such situations, delirium tremens may occur.

Signs of alcoholic hallucinosis

Alcoholic hallucinosis develops after abrupt cessation of prolonged and excessive alcohol use. Symptoms include auditory illusions and hallucinations, often of an accusatory and threatening nature; patients are often anxious and frightened by hallucinations and vivid, frightening dreams. The syndrome may resemble schizophrenia, although thinking is usually normal and there is no typical schizophrenia history. The symptoms are unlike the delirium of acute organic brain syndrome, nor are they like alcoholic delirium and other pathological reactions associated with withdrawal. Consciousness remains clear, and the symptoms of autonomic instability characteristic of alcoholic delirium are usually absent. When hallucinosis is present, it usually follows alcoholic delirium and is of short duration. Recovery usually occurs between the first and third weeks; relapses are possible if the patient resumes drinking.

Signs of alcohol delirium

Alcohol delirium usually begins 48-72 hours after alcohol withdrawal with anxiety attacks, increasing confusion, sleep disturbances (accompanied by frightening dreams and night illusions), pronounced hyperhidrosis and deep depression. Fleeting hallucinations are characteristic, which cause anxiety, fear and even horror. The states of confusion and disorientation typical for the onset of alcohol delirium can develop into a state in which the patient often imagines that he is at work and doing his usual business. Vegetative lability, manifested by sweating, rapid pulse, and increased temperature, accompanies delirium and progresses along with it. Mild delirium is usually accompanied by severe sweating, a heart rate of 100-120 beats per minute, and a temperature of 37.2-37.8 °C. Severe delirium with severe disorientation and cognitive impairment is accompanied by severe anxiety, a heart rate of more than 120 beats per minute, and a temperature above 37.8 °C.

During delirium tremens, the patient may misperceive various stimuli, especially objects in the dark. Vestibular disturbances may cause the patient to believe that the floor is moving, the walls are falling, and the room is spinning. As delirium progresses, tremors develop in the hands, sometimes spreading to the head and body. Ataxia is pronounced; observation is necessary to prevent self-harm. Symptoms vary from patient to patient, but are similar during exacerbations in the same patient.

Symptoms of Alcohol Withdrawal Syndrome

• Increased craving for alcohol
• Tremor, irritability
• Nausea
• Sleep disorders
• Tachycardia, arterial hypertension
• Sweating
• Hallucinosis
• Epileptic seizures (12-48 hours after last alcohol consumption)
• Delirium (rarely seen in uncomplicated withdrawal syndrome)
• Sharp excitement
• Confusion
• Visual hallucinations
• Fever, tachycardia, profuse sweating
• Nausea, diarrhea

Alcohol causes cross-tolerance to other sedatives and hypnotics, such as benzodiazepines. This means that the dose of benzodiazepines to relieve anxiety in alcoholics must be higher than in non-drinkers. However, when alcohol and benzodiazepines are combined, the combined effect is more dangerous than the effect of either drug alone. Benzodiazepines themselves are relatively safe in overdose, but when combined with alcohol, they can be fatal.

Chronic use of alcohol and other CNS depressants can lead to depression, and the risk of suicide among alcoholics is perhaps the highest compared to other categories of patients. Neuropsychological examination of alcoholics in a sober state reveals cognitive impairment, which usually decreases after several weeks or months of abstinence. More severe memory impairment for recent events is associated with specific brain damage caused by nutritional deficiencies, especially insufficient thiamine intake. Alcohol has a toxic effect on many body systems and easily penetrates the placental barrier, causing fetal alcohol syndrome, one of the most common causes of mental retardation.

Stages

Alcoholism has several classic stages.

Alcoholism: Stage I (from one year to three to five years):

• The level of tolerance to any alcoholic beverages begins to increase. A person can consume quite a large amount of alcoholic beverages, and the signs of intoxication will be the same as someone who drank three times less.
• Real alcoholism develops on the mental level. If there is no opportunity to drink for any objective reasons, a person displays all his most negative qualities - irritability, aggression, and so on.
• There is no normal self-defense reaction on the part of the body – the gag reflex to intoxication.

Alcoholism: stage II (from five to ten years, depending on the state of health and the functioning of the defense systems):

• Classic morning withdrawal symptoms begin – you want to drink to relieve the unpleasant symptoms after excessive drinking the night before. A hangover can be accompanied by typical signs of the second stage – tremors, changes in personality characteristics (a person is ready to humiliate himself to get what he wants). Such obsessions (compulsions) are a formidable sign of a entrenched disease. Unlike a healthy person who has overdone it with the dose and literally “dies” from all the classic symptoms of intoxication, an alcoholic experiences not just a craving for another dose, but a passion that is stronger than his mind and body.
• On the mental side, typical syndromes of disorder and disturbance of consciousness begin to appear. Sleep is usually superficial, accompanied by nightmarish visions similar to delusional ones. Character and personality traits change more noticeably, so that people around often say: "You have become completely different, not like your former self." Sensory disturbances develop - visual and hearing disorders. Often, a person at this stage becomes extremely suspicious, suspicious, jealous. Psychopathic manifestations can manifest themselves in the form of beliefs that someone is watching or following a sick person (delusional ideas about persecution). In the second stage, delirium (delirium tremens) is not uncommon. Physiological changes are also already obvious - gastroduodenitis, enlarged spleen, hepatitis of alcoholic etiology is possible. Libido decreases (in men, potency is impaired), memory is impaired, and often speech.

Alcoholism: Stage III (five to ten years):

• As a rule, this is the terminal stage, unfortunately, during which it is almost impossible to help the patient. Mental disorders are irreversible, as are the destruction of internal organs and systems. Cirrhosis, terminal stage of encephalopathy, dementia, atrophy of the optic and auditory nerves, extensive damage to the peripheral nervous system leave no hope not only for recovery, but also practically no chance of survival.

Treatment alcoholism

A chemically dependent person, and this is how a patient is usually called in the medical narcological environment, must be treated for a long time and in a comprehensive manner. Moreover, it is believed that alcoholism is a systemic disease in the social sense: if a person is surrounded by a family, then ideally all family members should attend special classes, sessions with a psychologist or psychotherapist. These people are considered codependent in the circle of the disease, that is, they also suffer, only without the participation of alcoholic beverages.

Of course, the effectiveness of therapeutic actions depends on the motivation of the patient himself. No matter how much the wife wants to rid her husband of his addiction, until he understands the tragedy of the situation himself and wants to change his life, all efforts will be limited to physiological remission. At the mental level, the addiction will remain at the same level, which is why there are breakdowns after drug treatment. Specialized medical rehabilitation centers are considered ideal conditions for treating patients with alcoholism, where the patient must stay for at least three months, or even longer.

Standard treatment methods include the following steps:

• Neutralization of withdrawal symptoms, detoxification;
• The use of various types of coding, the choice of which depends on the patient’s condition, length of use, and psychotype;
• Attending psychotherapy sessions – help from a psychologist, psychotherapist, it is better if it is a combination of individual and family therapy.

Treatment of acute alcohol intoxication

When people drink alcohol to the point of intoxication, the primary goal of treatment is to stop any further alcohol consumption, as this can lead to unconsciousness and death. A secondary goal is to ensure the safety of the patient and others by preventing the patient from driving or engaging in activities that may be dangerous due to alcohol consumption. Calm patients may become anxious and aggressive as their blood alcohol concentration decreases.

Treatment of chronic alcoholism

A medical examination is primarily necessary to diagnose concomitant diseases that may aggravate the withdrawal state and to exclude CNS damage that may be masked by or mimic withdrawal syndrome. Withdrawal symptoms should be recognized and treated. Steps should be taken to prevent Wernicke-Korsakoff syndrome.

Some medications used in alcohol withdrawal have pharmacological effects similar to those of alcohol. All patients with withdrawal may benefit from CNS depressants, but not all require them. Many patients can be detoxified without medications if appropriate psychological support is provided and the environment and contact are safe. On the other hand, these methods may not be available in general hospitals or emergency departments.

Benzodiazepines are the mainstay of treatment for alcoholism. Their dosage depends on the somatic and mental state. In most situations, chlordiazepoxide is recommended at an initial dose of 50-100 mg orally; if necessary, the dose can be repeated twice after 4 hours. An alternative is diazepam at a dose of 5-10 mg intravenously or orally every hour until sedation is achieved. Compared with short-acting benzodiazepines (lorazepam, oxazepam), long-acting benzodiazepines (e.g., chlordiazepoxide, diazepam) require less frequent administration, and their blood concentrations decrease more smoothly when the dose is reduced. In severe liver disease, short-acting benzodiazepines (lorazepam) or those metabolized by glucuronidase (oxazepam) are preferred. (Caution: Benzodiazepines may cause intoxication, physical dependence and withdrawal states in patients with alcoholism, so their use should be discontinued after the detoxification period. Alternatively, carbamazepine 200 mg orally 4 times a day, followed by gradual withdrawal, can be used.)

Isolated seizures do not require specific therapy; in recurrent seizures, diazepam 1-3 mg intravenously is effective. Routine administration of phenytoin is unnecessary. Outpatient administration of phenytoin is almost always an unnecessary waste of time and medication, since seizures occur only in the state of alcohol withdrawal, and patients who drink heavily or are in withdrawal do not take anticonvulsants.

Although delirium tremens may begin to resolve within 24 hours, it can be fatal and treatment must be started immediately. Patients with delirium tremens are highly suggestible and respond well to persuasion.

Physical restraint is not usually used. Fluid balance should be maintained, and large doses of vitamins B and C, especially thiamine, should be given immediately. A significant increase in temperature in alcoholic delirium is a poor prognostic sign. If no improvement is observed within 24 hours, other disorders such as subdural hematoma, liver and kidney disease, or other mental disorders may be suspected.

Maintenance treatment for alcoholism

Maintaining a sober lifestyle is a difficult task. The patient should be warned that after a few weeks, when he has recovered from the last binge, he may have an excuse to drink. It should also be said that the patient can try to drink alcohol in a controlled manner for a few days, rarely weeks, but eventually control is usually lost over time.

Often the best option is to enroll in a rehabilitation program. Most inpatient rehabilitation programs last 3-4 weeks and are held in a center that you are not allowed to leave for the duration of your treatment. Rehabilitation programs combine medical supervision and psychotherapy, including individual and group therapy. Psychotherapy includes techniques that enhance motivation and teach patients to avoid circumstances that lead to drinking. Social support for a sober lifestyle, including support from family and friends, is important.

Alcoholics Anonymous (AA) is the most successful approach to treating alcoholism. The patient must find an AA group that he or she feels comfortable in. AA provides the patient with non-drinking companions who are always available, as well as a non-drinking environment in which to socialize. The patient also hears confessions from other alcoholics about how they explained their drinking. The help the patient gives to other alcoholics helps to raise the patient's self-esteem and confidence, which alcohol had previously helped him or her achieve. In the United States, unlike other countries, many AA members do not join voluntarily, but are instead ordered by a court or on probation. Many patients are reluctant to come to AA, and individual counselors or family therapy groups are more appropriate. For those seeking other approaches to treatment, there are alternative organizations such as Life Circle Recovery (a mutual aid organization fighting for sobriety).

Drug treatment of alcoholism

Sedatives that have cross-tolerance to alcohol are also administered to reduce withdrawal symptoms. Because of possible liver damage, short-acting benzodiazepines such as oxazepam should be used in doses sufficient to prevent or reduce symptoms. For most alcoholics, oxazepam treatment should be started with a dose of 30-45 mg 4 times a day with an additional 45 mg at night. The dose is then adjusted depending on the severity of the condition. The drug is gradually discontinued over 5-7 days. After examination, uncomplicated alcohol withdrawal can be effectively managed on an outpatient basis. If somatic complications or anamnestic indications of epileptic seizures are detected, hospitalization is indicated. To prevent or reverse memory impairment, it is necessary to replenish nutritional and vitamin deficiencies, especially thiamine.

Drug treatment for alcoholism should be used in combination with psychotherapy.

Disulfiram interferes with the metabolism of acetaldehyde (an intermediate product of alcohol oxidation), resulting in accumulation of acetaldehyde. Drinking alcohol within 12 hours of taking disulfiram results in facial flushing within 5-15 minutes, followed by intense vasodilation of the face and neck, conjunctival hyperemia, throbbing headache, tachycardia, hyperpnea, and sweating. When consuming large doses of alcohol, nausea and vomiting may occur within 30-60 minutes, which may lead to hypotension, dizziness, and sometimes fainting and collapse. The reaction to alcohol may last up to 3 hours. Few patients will drink alcohol while taking disulfiram due to the severe discomfort. It is also necessary to avoid medications containing alcohol (eg, tinctures, elixirs, some over-the-counter cough and cold solutions, which may contain 40% alcohol). Disulfiram is contraindicated in pregnancy and in decompensated cardiovascular disease. It can be prescribed on an outpatient basis after 4-5 days of abstinence from alcohol. The initial dose is 0.5 g orally once a day for 1-3 weeks, then a maintenance dose of 0.25 g once a day. The effect may last from 3 to 7 days after the last dose. Periodic medical examinations are necessary to support the continuation of disulfiram as part of a sobriety program. Overall, the benefits of disulfiram have not been established, and many patients do not adhere to the prescribed treatment. Adherence to such treatment usually requires adequate social support, such as supervision of drug intake.

Naltrexone, an opioid antagonist, reduces relapse rates in most patients who take it chronically. Naltrexone is given at 50 mg once daily. It is unlikely to be effective without the advice of a physician. Acamprosate, a synthetic analogue of gamma-aminobutyric acid, is given at 2 g once daily. Acamprosate reduces relapse rates and the number of days of drinking if the patient is on a binge; like naltrexone, it is more effective when taken under physician supervision. Nalmefene and topiramate are currently being studied for their ability to reduce cravings.

Alcohol withdrawal syndrome is a potentially fatal condition. Patients usually do not seek medical attention for mild manifestations of alcohol withdrawal, but in severe cases, a general examination, detection and correction of water-electrolyte disorders, vitamin deficiency, especially the introduction of thiamine in a high dose (initial dose 100 mg intramuscularly) are necessary.

Alcoholism is much simpler, easier and cheaper to prevent at its earliest stages. Of course, this requires a systemic strategy at the state level. But the family can also do a lot in this area, starting from early childhood - instilling the basics of general culture, cultivating the ability to relieve stress in healthy ways - music, sports, creating a trusting atmosphere in the family without bias towards dictatorship or indulgence, permissiveness. The task is difficult, but the life story of an alcoholic can end even more dramatically, and even more tragically.

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Prevention

Detoxification is only the first step on the road to recovery. The goal of long-term treatment is complete abstinence - this is achieved primarily through behavioral methods. The ability of medications to facilitate this process is currently being carefully studied.

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Disulfiram

Disulfiram blocks the metabolism of alcohol, resulting in a buildup of acetaldehyde, which causes a subjectively unpleasant flush shortly after drinking. Knowledge of the possibility of this reaction helps the patient to refrain from drinking. Although disulfiram is quite effective pharmacologically, its clinical effectiveness has not been demonstrated in clinical trials. In practice, many patients stop taking the drug, either because they want to resume drinking or because they believe they no longer need the drug to stay sober. Disulfiram is still used in combination with behavioral techniques, voluntary or coercive, to persuade daily use of the drug. The drug appears to be useful in some cases.

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Naltrexone

Another drug used as an adjunct in the treatment of alcoholism is naltrexone. Opioid antagonists were first used in opioid addiction. By blocking opioid receptors, they weaken the effects of heroin and other opioids. Subsequently, naloxone (a short-acting opioid antagonist) and naltrexone were tested in an experimental model of alcohol addiction. This model was created in rats that were trained to drink alcohol to avoid electric shocks to their paws. Another model was created by selecting individuals with a tendency to alcohol, which was carried out over several generations. It was noted that some primates are more easily trained to choose alcohol in a free choice test - these animals were evaluated for the effects of opioid receptor antagonists. Both naloxone and naltrexone weakened or blocked the tendency to drink alcohol in these experimental models. Other studies have shown that alcohol activates the endogenous opioid system. Blockade of opioid receptors prevents the alcohol-induced increase in dopamine levels in the nucleus accumbens, the mechanism thought to be responsible for alcohol's rewarding effects.

Naloxone

These experimental data thus formed the basis for subsequent clinical trials of naltrexone in alcoholics treated in a one-day inpatient program. Naloxone, a short-acting opioid antagonist, is poorly absorbed when taken orally. In contrast, naltrexone is fairly well absorbed from the gut and has a high affinity for opioid receptors, with a duration of action in the brain of up to 72 hours. In an initial controlled clinical trial, naltrexone was shown to block some of the reinforcing effects of alcohol to a greater extent than placebo and to reduce craving for alcohol.

The same study showed that alcoholics taking naltrexone had significantly lower rates of relapse than those taking a placebo. These results were confirmed by other researchers, and in 1995 the FDA approved naltrexone for the treatment of alcoholism. However, it was emphasized that alcoholism is a complex disease, and naltrexone is best used as part of a comprehensive rehabilitation program. In some patients, the drug helps significantly reduce cravings and weaken the effects of alcohol if the patient “breaks down” and starts drinking again. Treatment should continue for at least 3-6 months, and the regularity of drug intake should be monitored.

Acamprostat

Acamprostate is a homotaurine derivative that can also help in the treatment of alcoholism. The drug's effectiveness has been proven in some experimental models of alcoholism and in double-blind clinical trials. According to experimental data, acamprostat acts on the GABAergic system, reducing post-alcohol hypersensitivity, and is also an NMDA receptor antagonist. It remains unclear why this action is useful in this situation, and whether the clinical effect of the drug is associated with it. In a large double-blind placebo-controlled study, acamprostat had a statistically more significant effect than placebo. The drug has already been registered in several European countries. It is important to note that acamprostat has a completely different mechanism of action than naltrexone, which allows us to hope for the possibility of summing up their effect when used in combination.

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