Cocaine, cocaine addiction: symptoms and treatment

Cocaine and other stimulants

The prevalence of abuse of psychostimulants varies cyclically, in contrast to the relatively constant level of abuse of opioids. In the last century in the US, two periods of high cocaine popularity were noted. The last peak of his popularity occurred in 1985, when the number of people occasionally taking cocaine reached 8.6 million people, and the number of people who regularly took this substance was 5.8 million people. More than 23 million Americans have ever taken cocaine in their lives, but the number of people who continued to take cocaine gradually declined to 2.9 million in 1988 and 1.3 million in 1992. The middle of the 90s can be considered as a late phase of the epidemic. Since 1991, the number of people who frequently use cocaine (at least weekly) remains stable and amounts to 640,000 people. Approximately 16% of people who tried cocaine lost control at some point and became addicted. Some factors that influence the transition from cocaine use to cocaine abuse and further to cocaine addiction were discussed at the beginning of this chapter. Among them, the availability and cost of the drug are critically important. Until the 1980s, cocaine hydrochloride, suitable for intranasal or intravenous administration, was the only available form of cocaine, and also quite expensive. The appearance of cheaper cocaine alkaloids ("free base", "crack"), which could be administered by inhalation. In addition, they could easily be purchased in most major cities for 2-5 dollars per dose. Thanks to this, cocaine became available to children and adolescents. In general, substance abuse is more common in men than in women, and cocaine is approximately 2: 1. However, the use of "crack" is very common among young women and reaches a level characteristic of men. In this regard, the prevalence of cocaine use among pregnant women is quite high.

The reinforcing effect of cocaine and its analogues is best correlated with the ability of the drug to block the dopamine transporter providing its presynaptic re-uptake. The transporter is a specialized membrane protein that re-captures the dopamine secreted by the presynaptic neuron and replenishes the intracellular stores of the neurotransmitter. It is believed that the blockade of the transporter enhances dopaminergic activity in critical areas of the brain, prolonging the residence of the mediator in the synaptic cleft. Cocaine also blocks transports that provide for the reuptake of noradrenaline (HA) and serotonin (5-HT), so long-term cocaine intake also causes changes in these systems. Thus, the physiological and mental changes caused by cocaine intake can depend not only on the dopaminergic, but also on other neurotransmitter systems.

The pharmacological action of cocaine in humans is well studied in the laboratory. Cocaine causes a dose-related increase in heart rate and increased blood pressure, which is accompanied by increased activity, improved performance of tests for attention and the emergence of a sense of self-satisfaction and well-being. Higher doses cause euphoria, which is short-lived and gives rise to a desire to re-take the drug. There may be involuntary motor activity, stereotypes, paranoid manifestations. People who take long doses of cocaine for a long time are noted for irritability and outbreaks of aggression are possible. A study of the status of dopamine D2-receptors in hospitalized patients who had been using cocaine for a long time revealed a decrease in the sensitivity of these receptors, which persisted for many months after the last cocaine intake. The mechanism and consequences of decreasing receptor sensitivity remain unclear, but it is believed that it may be associated with the symptoms of depression experienced in individuals who previously used cocaine and are often the cause of relapse.

The half-elixion period of cocaine is about 50 minutes, but the desire to take an additional dose of cocaine from people smokers "crack" usually occurs after 10-30 minutes. With intranasal and intravenous administration, there is also a short-term euphoria that correlates with the level of cocaine in the blood and suggests that, a decrease in concentration is accompanied by a cessation of euphoria and the appearance of a desire to receive a new dose. This theory is supported by positron emission tomography (PET) data using a radioactive preparation of cocaine containing the isotope "C, which shows that during the sensation of euphoria, capture and movement of the drug into the striatum is noted (Volkow et al., 1994).

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

Cocaine Toxicity

Cocaine has a direct toxic effect on organ systems. It causes disturbance of the heart rhythm, myocardial ischemia, myocarditis, aortic dissection, cerebral vasospasm, epileptic seizures. Taking cocaine with pregnant women can provoke premature birth and placental abruption. Cases of developmental abnormalities in children born to mothers who consumed cocaine were reported, but they could also be associated with other factors, for example, miscarriage, exposure to other substances, poor prenatal and postnatal care. With intravenous administration of cocaine, the risk of various hematogenous infections is increased, but the risk of sexually transmitted infections (including HIV infection) is increased even when smoking crack cocaine or intranasal cocaine.

It was reported that cocaine causes a prolonged and intense orgasm, if it is taken before sexual intercourse. Its use, therefore, is associated with sexual activity, which often takes a compulsive and disorderly character. However, with prolonged use, there is often a decrease in libido, and among people who use cocaine and seek treatment, complaints about sexual disorders are not uncommon. In addition, among people who abuse cocaine and seek treatment, often there are mental disorders, including anxiety, depression, psychosis. Although some of these disorders undoubtedly existed before the use of stimulants, many develop already against the background of cocaine abuse.

[5], [6], [7], [8],

Pharmacological aspects of cocaine use

Repeated use of the drug usually causes adaptive processes in the nervous system, and the subsequent administration of the same dose causes a less significant effect. This phenomenon is called tolerance. Acute tolerance, or tachyphylaxis, is the weakening of the effect with a rapid re-injection of the drug. Acute tolerance develops in an experiment in both humans and animals. With intermittent use of the drug, for example, once a single dose is administered, once or twice a day, opposite changes may occur. In the study of psychostimulants (such as cocaine or amphetamine) in experimental animals (for example, rats in whom behavioral activation was evaluated) with repeated administration of the drug, its effect was enhanced, rather than weakened. This is called sensitization - the term means increased effect when the same dose of the stimulant is repeated. Persons using cocaine and seeking treatment did not report the possibility of sensitization with respect to the euphorogenic effect of the drug. Sensitization was not observed in humans and in laboratory studies, although no special experiments were conducted to detect this effect. On the contrary, some experienced cocaine writers reported that, in time, they required ever-higher doses to achieve euphoria. This indicates the development of tolerance. In the laboratory, tachyphylaxis (rapidly developing tolerance) with a weakening effect was observed when the same dose was administered during one experiment. Sensitization can be conditioned-reflex. In this connection, it is interesting that people who use cocaine often report a strong effect associated with visual perception of the dose and which occurs before the drug enters the body. This reaction was investigated in the laboratory: people who used cocaine and were in abstinence condition were shown videos with scenes associated with taking cocaine. Conditionally reflex reaction consists in physiological activation and strengthening of craving for the drug.

Sensitization in humans can also underlie the paranoid psychotic manifestations that occur with cocaine use. This assumption is confirmed by the fact that paranoid manifestations associated with "drinking" occur only after long-term use of cocaine (an average of 35 months) and only in predisposed individuals. Thus, the re-introduction of cocaine may be required to develop sensitization and the appearance of paranoiac symptoms. The phenomenon of Kindling is also involved in explaining cocaine sensitization. The repeated administration of subconvulsive doses of cocaine eventually leads to epileptic seizures in rats. This observation can be compared with the process of kindling, leading to the development of epileptic seizures with subthreshold electrical stimulation of the brain. It is possible that a similar process explains the gradual development of paranoid symptoms.

Since cocaine is usually used sporadically, even people who use cocaine often have frequent episodes of withdrawal, or "withdrawal". Manifestations of the withdrawal syndrome observed in persons with cocaine addiction. A thorough study of the cocaine withdrawal syndrome showed a gradual weakening of the symptoms within 1-3 weeks. After the end of the withdrawal period, residual depression may occur, with prolonged maintenance of which antidepressant treatment is required.

Cocaine abuse and dependence on it

Dependence is the most frequent complication of cocaine use. Nevertheless, some individuals, especially those who inhale cocaine intranasally, may occasionally consume the drug for many years. In others, the use of the drug becomes compulsive, despite carefully thought out measures to limit admission. For example, a medical student can swear that he will use cocaine only on weekends, and the lawyer will make a firm decision that he will not spend more than cocaine that can be received through an ATM. But gradually these restrictions stop working, and people start taking cocaine more often or spend more money on it than previously thought. Psychostimulants are usually taken less regularly than opioids, nicotine or alcohol. Cocaine "drinking" is often observed, which can last from several hours to several days and ends only when the stock of the drug runs out.

The main pathway of cocaine metabolism is the hydrolysis of each of its two ester groups, leading to a loss of its pharmacological activity. Benzoylecgonine-demethylated form is the main metabolite of cocaine found in urine. Standard laboratory tests for the diagnosis of cocaine use are based on the detection of benzoylecgonine, which can be detected in the urine 2-5 days after the "binge". In people who consume high doses of the drug, this metabolite can be found in the urine and after 10 days. Thus, a urine test can show that a person has been using cocaine in the last few days, but not necessarily at the present time.

Cocaine is often used in combination with other substances. Alcohol is another drug that cocaine users use to reduce the irritability experienced by taking high doses of cocaine. In some, in addition to cocaine addiction, alcohol dependence also develops. With the simultaneous intake of cocaine and alcohol can interact with each other. Some of the cocaine is transesterified into cocaethylene, a metabolite that is not inferior to cocaine in its ability to block the re-uptake of dopamine. Like cocaine, cocaine increases locomotor activity in rats and easily causes addiction (spontaneous consumption) in primates.

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

Symptoms of Cocaine Abstinence Syndrome

• Dysphoria, depression
• Drowsiness
• Fatigability
• Increased craving for cocaine
• Bradycardia.

Anticonvulsant carbamazepine is proposed for treatment, based on its ability to block the process of Kindling - a hypothetical mechanism for the development of cocaine addiction. However, in several controlled trials, the effect of carbamazepine has not been demonstrated. Recent studies have shown that disulfiram (probably due to its ability to inhibit dopamine-beta-hydroxylase) can be useful in treating cocaine dependence in patients with comorbid alcoholism and opioid abuse. There have been reports of the ability of fluoxetine, a selective serotonin reuptake inhibitor, to cause a statistically significant reduction in cocaine use, as measured by measuring the urinary level of the metabolite of cocaine benzoylecgonine compared with placebo. It is noted that buprenorphine, a partial agonist of opioid receptors, inhibits the spontaneous use of cocaine by primates, but in a controlled trial in patients who were simultaneously dependent on opioids and cocaine, there was no decrease in cocaine use. Thus, all studied drugs that help prevent the recurrence of cocaine dependence, at best have a moderate effect. Even a slight improvement is difficult to reproduce, and it is now generally accepted that there is no drug that would effectively help in the treatment of cocaine addiction.

Drug treatment of cocaine addiction

Because cocaine abstinence is usually mild, it often does not require special treatment. The main task in the treatment of cocaine dependence is not so much to stop using the drug, but how to help the patient resist the urge to return to compulsive use of cocaine. According to some reports, rehabilitation programs, including individual and group psychotherapy and based on the principles of the society "Alcoholics Anonymous" and methods of behavioral therapy (using the study of cocaine metabolites in urine as a confirmatory test), can significantly improve the effectiveness of treatment. Nevertheless, there is great interest in finding a drug that could help in the rehabilitation of people with cocaine addiction.

Desipramine is a tricyclic antidepressant that has been tested in several double-blind studies with cocaine addiction. Like cocaine, desipramine inhibits the re-uptake of monoamines, but mainly acts on noradrenergic transmission. According to some assumptions, desipramine can alleviate some of the symptoms of cocaine withdrawal and an addiction to cocaine within the first month after cessation of its use - at a time when relapses are especially frequent. Desipramine had a clinically significant effect in the early period of the epidemic when used in a group that mainly included "white-collar workers" and used intranasal cocaine. The results of subsequent studies on the efficacy of desipramine in individuals who injected intravenously cocaine or smoked crack were ambiguous. According to some sources, beta-blocker propranolol can reduce the symptoms of withdrawal from cocaine dependence.

Among other drugs, the effectiveness of which has been shown, mention should be made of amantadine-dopaminergic, which may have a short-term effect in detoxification

[12], [13], [14], [15], [16], [17],