Stimulant Pharmacokinetics

Stimulating drugs can be introduced into the body and absorbed in different ways, and accordingly have different strength and duration of action. Cocaine, amphetamines and similar stimulants (methylphenidates, phenthrazine) are well absorbed through the stomach, but the result is slower and it is noticeably weaker than if taken in other ways. Both cocaine and amphetamines are usually inhaled through the nose, and they are absorbed almost as quickly as they are ingested. In this case, the action begins after 5-15 minutes, while with intravenous injection, stimulants give a strong effect after 30 seconds. When smoking cocaine in the form of crack, the result comes even faster.

An important difference between cocaine and amphetamines is the duration of action. Cocaine metabolism occurs quickly: after 20-80 minutes, all its effects disappear. Cocaine metabolites can be detected in the urine within 2-3 days of administration. Amphetamines act from 4 to 12 hours, although their metabolites disappear from the urine after 2-3 days.

The mechanism of stimulating action

As mentioned in Chapter 3, stimulants such as cocaine and amphetamines act on the brain mainly through the interaction with the monoamine neurotransmitters dopamine, norepinephrine and serotonin. Both cocaine and amphetamines block the reuptake of norepinephrine and dopamine. In addition, they appear to increase the release of norepinephrine and dopamine into the synapse. Cocaine also inhibits serotonin reuptake. Thus, initially, stimulants cause a storm in the transmission channels of nerve impulses sensitive to monoamine mediators. As a result of increased neuronal activity and, in particular, due to blocking reverse absorption, the long-term effects of stimulant intake include depletion of monoamine reserves. If we recall that a low level of monoamine content in the brain is associated with clinical cases of depression, it becomes clear why among the consequences of consuming large doses of cocaine are depression. To substantiate this hypothesis, we turn to the data of animal experiments.

It has long been known that animals love cocaine. Rats and monkeys will prefer cocaine to any other drug and, under certain circumstances, even food. Obviously, the strong invigorating effect of cocaine and amphetamines comes from the fact that they interact with the dopamine-containing neurons of the nerve channels that make up the central node of the anterior brain. As you remember from Chapter 3, this part of the brain is responsible for the feeling of pleasure, and cocaine can be called the catalyst of processes in the pleasure system. Since the long-term use of the drug depletes the reserves of dopamine (and other mediators important for depression), then a person’s ability to experience normal pleasure decreases. This is associated with depression, which so often accompanies cocaine abstinence and is known as “cocaine sadness.” Figure 6-1 shows the relationship between cocaine and mood with moderate and heavy use. The left peak of the curve corresponds to a rise in mood after taking cocaine, a fall on the right side of the graph means a subsequent depression. After a large dose, depression is stronger. This is true as with one dose, and with prolonged use. The longer a person has taken a drug, the stronger and longer his depressive withdrawal syndrome will be.

Second cocaine epidemic

It is said that those who do not learn from mistakes are doomed to repeat them. In the case of cocaine, this is true. Why of all stimulants, the choice fell again on cocaine? In the early 70s, cocaine was quite difficult to get, and it cost a lot of money. He was known as a drug of movie stars and athletes (the few who could afford to spend such money), and had a reputation as “champagne among stimulants.” At this time, cocaine was mostly smelled in small doses, and rarely encountered problems with intravenous injections. There were, of course, trouble. For example, the former Dallas Cowboys defender, football player

Hollywood Henderson, admitted that he had acquired a habit that costs him $ 1,000 a day, but there were relatively few such victims of cocaine. Cocaine was considered quite a harmless drug. There were books in which it was written that cocaine “is not addictive, as dangerous drugs”, many advocated its legalization.
Nowadays, there is not the slightest doubt that cocaine is a very dangerous drug. Words like the ones above seem terribly naive, because we see how many people died from cocaine overdose, we have names of celebrities trying to recover from cocaine addiction. What has changed? One of the reasons was the appearance of cheap cocaine. Now it began to be consumed by more people and in large doses. Another important factor was the spread of crack. Crack knew in the late 70s, and in 1986 it just broke into the life of American society.

Yet cocaine is usually consumed in a cleaner form. Regular cocaine, which can be bought on the street, is a white powder. A paste is made from coca leaves, into which hydrochloric acid is poured, and cocaine hydrochloride is obtained. Since street cocaine is salt, it is readily soluble in water and can be injected with a syringe into a vein. Cocaine can be sniffed, and in this way it produces a rather strong effect, but since the drug constricts the blood vessels in the nose, it is slowly absorbed. By the way, this narrowing of the blood vessels can cause inflammation and damage to the nasal mucosa. With the introduction of cocaine through the nose, psychosis also occurs, deaths in overdose, etc., but less often than if administered intravenously. Therefore, until the end of the 80s, while the main method of cocaine use was the way through the nose, the danger of this drug was underestimated.

In the process of smoking cocaine, it is absorbed through the lungs completely and very quickly and causes very pleasant and very short sensations, followed by a strong breaking. But at the high temperature required for smoking, cocaine in the composition of the salts is destroyed. In order for cocaine to be smoked, it is necessary to separate the cocaine base from the hydrochloride (get “free cocaine”). One way is to mix the salt of cocaine with the flammable substance ether. Many people who could not handle him were badly burned. However, crack can be obtained in a simpler and safer way – by dissolving the salt of cocaine in an alkaline solution, for example in baking soda. After evaporation, you get a crack. It has a low melting point, and therefore it can be heated and inhaled smoke containing intact cocaine. (The name “crack” comes from the English “crack” – “crackling”, as when the mixture is heated, a crackling sound is produced by soda remaining in the compound.) When smoking crack cocaine quickly gets into the brain, causing such a quick rise and such pleasant sensations, that many addicts prefer it to comparable doses of cocaine, which must be administered intravenously. This euphoria is short-lived, and after 10-20 minutes, the person is eager to introduce another dose. Researchers note that the desire to take the next dose in people who smoke crack is higher than that of intravenous cocaine.

Crack is cheaper and less dangerous in production than other types of “free” cocaine, so drug dealers distribute it. In addition, it is so potent that it can be sold in small portions for 10-20 dollars, which means that it is relatively affordable. Crack is very addictive, and it does so quickly, so in one instant a large market of this drug formed. Crack came to the attention of the media at the end of 1985, and at the beginning of 1986 Time, Newsweek and television spoke of it as a national disaster. In the late 1980s, millions of Americans consumed crack. When two well-known athletes, Len Bias and Don Rogers, were killed in one week from an overdose of cocaine, it became clear again that cocaine must be fought. Cocaine is lethal, especially in the form of crack. At this time, other consequences of overdose, in particular the development of paranoia, became very frequent. In 1990, there were more than 80,000 ambulance calls related to cocaine use (compared to 10,000 in 1985 and almost absent in 1970). With the spread of crack Cain addiction has become a major health problem.

Crack and cocaine still have a strong influence on society. One of the sides of the problem is the incredible increase in the activity of the underworld associated with cocaine. Cocaine sales are controlled by large and well-organized criminal groups, known as cartels. The largest of these, the Cali cartel, is in Colombia. He supplies most of the cocaine to the United States. When the governments of the United States and Colombia declared war on drug smuggling, this resulted in a series of armed clashes. In the first half of 1989, more than two thousand people were killed in Medellín (Colombia). Hundreds of judges and members of the judiciary were the victims of attempts, hundreds of others resigned. Although the head of the Medellín cartel, Pablo Escobar, was killed in a shootout with the police in 1993, the cartels continue to expand, covering Eastern European and Asian countries, and are becoming global. Newsweek wrote in 1993: “The annual income of organized crime is estimated at $ 1 trillion, which is almost equal to the annual federal budget of the United States. The Cali cartel tried to launch its own satellite into space to avoid tapping the CIA’s telephone conversations.”

In the United States itself, cocaine goes hand in hand with crime and violence. The famous Los Angeles gangs “Blades” and “Crips” have absorbed groups from other cities and are fighting with other groups (from Jamaica and other Latin American countries) for control of the crack market. These well-organized groups represent a great danger to citizens and a headache for the police. Unlike the former small drug dealers, gang members have well-armed and sophisticated systems for transporting their goods. Many cases of shootings on the roads and other urban violence are related to crack.

Crack has an exceptional effect on people of its destructiveness. Dependence on him brings people to extreme despair and self-destruction. “Crack houses” – the places where crack is sold and smoked – became in the 90s the den of lawlessness. When a drug addict runs out of money, sexual services of a different kind become a means of paying for crack, and an additional risk factor appears – AIDS. In special studies of the life of “crack houses”, one can find indications of numerous cases of murder, rape, child prostitution, etc., the usual things for these places.

A good idea of ​​them will give the words of one addict:

In the houses of crack I have seen things that I have not seen anywhere else. Worse places can not be imagined. No one cares about anyone, do what you want. What did I not see! I saw a girl that ______ fifty times, until she was already covered in blood and could not even get up, and this is for a small piece of crack. I saw one guy splashed acid on her face, just because she didn’t want to sleep with him anymore. I saw a single shot of an egg shotgun for trying to steal some crack. Hey, man, these are bad places … ”
In recent years, an extensive campaign against crack has been launched, a description of all the dangers cannot be ignored. Why do people still smoke crack?

The following seductive and ominous description belongs to the person who smokes crack:

“Imagine that you are on the island, and about ten meters from the coast there is a sort of orange-pink mist, sparkling and alluring. You enter the cold, dark water and float to this blazing cloud, and here you are near, and you already feel the heat, and you well, but the fog is a little distant. You dive and you are almost in its very center, and it’s so beautiful. But now the fog drifts into the sea faster, and you need to swim faster and faster to catch up with it, and you are further and further from coast. That’s the way it is with crack. After the first puffs you feel good, you draw deep – and you are in the middle e, and you have fun, but then you let go and you need more. Very soon you find yourself the devil knows where, in the cold dark ocean, and you have to quickly swim to this warm, wonderful, sparkling fog, which you can never reach, or turn back and swim for miles in this dark cold water. “


After Harrison’s law, cocaine consumption in America began to decline, but a new stimulant, amphetamine, soon appeared on the scene. This is a class of drugs that includes amphetamine, dextroamphetamine and methamphetamine. They were first synthesized in the late 19th century, and, although they were immediately available for research, their medical use began only in the 1920s. It was believed that they are useful in the treatment of colds, obesity, narcolepsy (a disease in which a person falls asleep uncontrollably). They, oddly enough, were also used to treat hyperactive children. Amphetamines are now rarely used in medicine, mainly because they are very easy to abuse. These drugs were used as stimulants during World War II on both sides of the front. After the war, amphetamine abuse reached epidemic proportions in Japan, Sweden and some European countries, but in America until the 1960s they were not considered dangerous drugs. Ironically, they became America’s headache when doctors began to prescribe them as a cure for heroin addiction. As with the cocaine treatment of morphineism, undertaken by Freud, this innovation turned into a surge in the abuse of amphetamines, especially on the west coast.
Injection of amphetamines leads to addiction, similar to cocaine problems at the beginning of the century (and which we see now). Immediately after the injection, a person experiences a short but strong rise or “arrival”. The very pleasant sensations that occur after the injection of cocaine or amphetamine are often described as orgasmic in nature. But since they do not last longer than a few minutes, the person soon wants to return to the heights of bliss again, although the level of the drug in the blood is still quite high. Several injections follow one after another, the person becomes more and more excited, but it becomes more difficult to achieve the same pleasant recovery as the first time. Both cocaine and amphetamines suppress appetite and interfere with sleep, and therefore a person can not sleep for days, eat very little, and at the same time inject himself dose by dose. In the 1960s, such people were called “speed freaks” (speed freak). With their appearance, it became clear that amphetamine has almost all the properties of cocaine. For example, after taking a large dose of amphetamine, a person also feels goosebumps, as well as overdose of cocaine, and paranoid hallucinations appear, that is, amphetamines can cause a psychosis almost identical to cocaine.
Here is a description of a typical fast eccentric from San Francisco: “He’s a very nice man and very generous. However, when he smacks … he starts having problems. Because he has a shotgun very quickly in his hands … I saw him he drove the hitchhikers from the highway exit: they cause him paranoia. At four o’clock in the afternoon, he yells with a huge shotgun in his hand “come on, come on, get out of here, you can’t stand here.”
This paranoid psychosis caused by an overdose of cocaine and amphetamines can be called stimulatory psychosis.
In the late 60s they wrote “Speed ​​is killing!” The slogan does not imply that death comes from an overdose. Deaths from amphetamine overdose have occurred, but comparatively rarely. The paranoid state, which often leads to the commission of an act of violence, develops much more often. In addition, after taking large doses of amphetamines, a person “breaks down” (falls asleep for a long time), and when he wakes up, he finds himself in a state of severe depression. It can last several days and is an abstinence syndrome after heavy use of amphetamine or cocaine. To overcome depression, a person often takes a drug again, and everything repeats from the beginning. Ultimately, the physical and mental state of a person is seriously deteriorating, and the person is no longer able to break this circle.
When the risk to which a person is exposed when using amphetamines became apparent, other, less dangerous stimulants were sought. In the 1970s, amphetamines-related phenmetrazine became popular. Soon, however, it turned out that it causes all the same side effects. By the mid-1970s, another tendency was revealed: a “new” stimulant, an “organic”, a “natural” or a “natural” drug appeared on the scene – of course, because there can be nothing wrong with … cocaine?

Early use of cocaine

The further history of cocaine is very curious. It was attended by one young Viennese doctor who needed some kind of discovery to gain recognition.
Although now Sigmund Freud is better known as a researcher of another problem, his first work was devoted to cocaine. Freud tried cocaine in 1884 and soon realized that he had discovered an amazing substance. In his first major publication, O Coke, he promoted cocaine as a local anesthetic and a cure for depression, indigestion, asthma, various neuroses, syphilis, drug addiction and alcoholism. He also believed that cocaine increased sexual arousal.

Of this list of possible medical indications of cocaine, only one was valuable – for local anesthesia. When cocaine molecules interact with neurons of the peripheral nervous system, the latter cannot be excited, which causes numbness in some part of the body. Cocaine acts on the central nervous system quite differently. Cocaine became the first local anesthetic, and this revolutionized surgery. Nowadays, of course, cocaine derivatives are more widely used, such as procaine or novocaine. But cocaine itself is still used in surgery, especially in face surgery, as it constricts blood vessels, reduces bleeding and reduces pain.
Freud’s early thoughts about cocaine were erroneous and led to a wave of abuse of this drug. It’s funny, but the first to demonstrate what people expect in the future was Freud’s friend Ernst von Fleischel. He suffered from chronic pain, and because of this he became a morphine. Freud undertook to cure him and prescribed cocaine. Fleischel began to consume it in more and more large quantities and, indeed, got rid of the addiction to morphine. But his daily dose of cocaine soon amounted to one gram. Fleishel became the first cocaine in Europe. He had strange symptoms, which, as we now know, are the result of cocaine overdose. Among them were paranoid hallucinations, which are often observed in paranoid schizophrenia, and itching of the skin, so-called “goosebumps”, in which a person feels as if insects or snakes crawl on his skin. These symptoms are the result of a cocaine overdose, and the first of many who experienced these sensations was Fleischel.

Freud was amazed at the devastating effect that cocaine had on Fleischel, and in the following articles he diminished his enthusiasm for cocaine. But the harm was already irreparable. It was a cocaine epidemic of the 80s, yes, yes, it was the 80s of the XIX century! Doctors prescribed cocaine; in pharmacies without someone’s prescription, patented drugs containing it were sold (for example, Mariani coca wine, a record holder in sales in Europe). And, of course, cocoa. Older advertisements say that this drink “contains tonic and stimulating substances from coca plants.” Cocaine took a place in music and literature: he gave Sherlock Holmes vivacity and improved deductive abilities; Stephenson apparently wrote a story about Dr. Jackel and Mr. Heide during his cocaine treatment for tuberculosis. Good recommendations cocaine gave Thomas Edison, Jules Bern, Emile Zola, Heinrich Ibsen and President Grant.

The Cocaine Metcalfe wine ad shows how cocaine became so popular: Speakers, singers and actors found that coca wine strengthened the vocal cords well. Athletes, runners and baseball players on their own experience were convinced that prolonged use of coca, both before and after the competition, gives strength and energy and reduces fatigue. Older people have learned that this is a reliable aphrodisiac, the best of all known.

With such an advertisement, cocaine was not difficult to become popular. With the increase in the number of people who use drugs, danger has become noticeable. Many discovered these dangers on themselves, and after cocaine psychosis, deaths from overdoses, and heavy drug addiction, public opinion came out against cocaine. One of the works that most impressed the public and changed the perception of cocaine was an article that dealt with the case of Annie Meyer, who was a successful business woman and a “balanced Christian” until she became a “friend of cocaine.” Meyer described well all the power of cocaine addiction. It was a period when she ran out of money. “I took the scissors and loosened my golden tooth. Then I pulled it out, flattened it and rushed to the nearest pawnshop (blood flowed down my face, the dress was wet with blood), where I sold the tooth for 80 cents.” After that, attitudes toward cocaine began to change. Reports of rape committed under the influence of cocaine were added to the dramatic descriptions of drug addiction, and public opinion exploded. The culmination of indignation was the adoption in 1914 of Garrison’s cocaine control law. Initially, the law was intended to control the spread of opiates,like morphine and heroin, but the inclusion of cocaine in the list of dangerous drugs was by no means accidental.

Cocaine and Incas

Drug use dates back to prehistoric times. The Incas, who lived on the territory of modern Peru and Bolivia, apparently adopted the custom of chewing coca leaves from Aymara Indians, who used coca from at least the 3rd century BC. Coca was the sacred drug of the Incas. “Mama Kok” was for them a godlike entity. One of the myths says that coca was a beautiful woman who was punished for adultery. From carrying the divine coca plant occurred, chewing its leaves could only know, and this was done in memory of a beautiful woman. Indeed, before the invasion of the Spaniards, the coca was consumed only by the highest strata of society. She was an important part of weddings, funerals, initiations, and other major rites. Spanish missionaries looked askance at Coke, because it seemed to them an idol, which prevented the conversion of the natives to the Christian faith. But coca played such an important role in Native American society that, over time, the Spaniards took its collection and distribution under their control, making the drug a means of controlling the indigenous population.
“Cocaine causes … excitement and prolonged euphoria”
Freud about cocaine.

Coca leaves

High in the Andes Mountains of Peru and Bolivia, a low shrub grows, which is called a tree or coca bush (Eryhoxylum coca). From the leaves of this plant is a potent stimulant – cocaine. The history of this drug is rooted in antiquity. Locals – the Incas and their historical successors – have been chewing coca leaves for centuries. It is not known exactly when cocaine use began. Archeology data allows us to give an approximate figure of several thousand years ago. Coca leaves played an important role in the religious rites of the Incas, and also used for medicinal purposes and just in the process. When the Spanish conquistadors encountered the Inca civilization in the 16th century, they initially fought against the use of coca for religious purposes, for this went against the Catholic faith. But having finished the conquest of the Inca Empire, the Spaniards allowed the use of coca and even encouraged it: because they saw that by chewing its leaves, the Indians could work better and longer. In the end, the Spaniards established control over the use of coca by starting to use its leaves as a means of payment: the Indians paid them some taxes. The Spaniards considered chewing coca a sin and therefore did not use it themselves and did not distribute it among other Europeans.

Thus, until the XIX century, Europe almost did not know about the existence of the coca tree. But when European naturalists reached Peru, they became acquainted with this plant, and soon strange and often contradictory stories spread about it. In some, like the German naturalist Edwin Poppig, coca leaves were called deadly: “Chewing coca has the most disastrous consequences, causing the same poisoning as opium. With each time, desire increases, and the strength to resist decreases, and so on, until death will save the unfortunate from suffering. ” Other authors, like the Italian biologist Mantegazza, who himself, while in Peru, chewed on a coca, treated this plant more positively: “I laughed at mere mortals doomed to live in this valley, while I was swept away on the wings of two leaves Coca and flew through 77.438 worlds, each of which was more delightful than the previous one. ”

Neither quotation is a sufficiently correct description of the effect of coca leaves on humans. Nevertheless, Mantegazza’s point of view was much more attractive: in almost all historical studies, the growth of scientific interest in coca is associated with this Italian. The result of scientific interest was the appearance of coca leaves in laboratories, and in the 50s of the XIX century, European chemists were able to isolate a potent substance called cocaine from the leaves. This opened up a new era in the history of stimulant drug use. The fact is that cocaine in its pure form is very effective, while the coca leaf itself contains a very small amount of this drug. In addition, it produces a different and stronger effect if administered intravenously or sniff, which is possible only if there is an extract. Obviously, intravenous injection of cocaine produces the most powerful effect, because a large amount of the substance reaches the brain very quickly.

The mechanism of action of opiates

One of the most outstanding achievements in neurology was the discovery in the 70s of the neural mechanism of action of opiates. Research on this topic led to the discovery of a class of chemicals secreted by the brain, called endorphins, which obviously function as neurotransmitters. According to modern concepts, the action of morphine, heroin and other opiates is caused by stimulation of the action of the endorphin system in the brain. After reviewing the events that led to these discoveries, you can see how they help to understand the actions of the opiates.

One of the first events was the discovery by chemists in the 60s. the fact that the slightest change in the morphine molecule causes the creation of a chemical that not only does not produce any of the typical effects of opiates (relief of pain, euphoria), but, on the contrary, blocks the action of morphine and other opiates. This substance is called naloxone (Narcane) and can be qualified as an opiate antagonist. When naloxone was given to a patient suffering from a heroin or morphine overdose, he completely reversed the effects of these drugs. If naloxone is given to a heroin recipient, then heroin will have no effect. Obviously, naloxone has practical application in the treatment of opiate overdose and also has theoretical value. Since the chemical structure of naloxone is similar to morphine, the researchers suggested that these two drugs may act on some common brain receptor, and the effect of morphine on this receptor is blocked by naloxone. In the early 70s. two researchers from Johns Hopkins University in Baltimore, Candace Perth and Solomon Snyder reported on the discovery of brain receptors that selectively respond to the effects of opiates and called them “opiate receptors.” The existence of such receptors has caused great interest. It may be reasonable to ask why there are neurons in the brain responsible for the effects of such drugs. Did nature itself push people to become addicted to heroin? The presentation of neurologists on this subject varied greatly. They believed that the presence of such receptors should mean that there are natural substances in the brain with a structure and properties resembling morphine. The scientific search began for “natural brain opiates” and in 1975 several such substances were discovered. Although several morphine-like substances were found in the brain (beta-endorphin, enkephalin, dinorphin – the most important among them), the whole complex of these peptides is collectively called endorphin (short name for endogenous morphine).

The scientific questions caused by the discovery of endorphins focused on why the brain is provided with its own morphine, what function they perform. Most researchers began with the premise that because opiates mimic the activity of endorphin by stimulating the opiate or endorphin receptors in the brain, endorphins should have many properties similar to opiates, such as the ability to relieve pain or pleasure. Perhaps the main function of endorphins is to serve as part of the natural pain relief system. According to modern concepts, certain types of pain or stress cause the release of endorphins, and an analgesic effect occurs. Such an approach may help explain why under certain circumstances, for example, on the battlefield or in a big sport, a person can withstand severe injuries without feeling pain for at least some time. Pain relief from acupuncture (through needle insertion) may also be caused by the release of endorphin, since the use of naloxone negates the anesthetic effect of acupuncture. Since the main action of naloxone is blocking endorphin receptors, the anesthesia, negated by naloxone, is strong evidence that acupuncture needles cause the release of endorphins and thereby reduce pain.

It seems that strength training causes the release of endorphins, and perhaps some of the positive effects of these exercises on your mood are also caused by the action of endorphins. Indeed, some researchers believe that “dependence” on exercise, which develops in some people, is due to the same mechanisms in the brain, due to which there is also a dependence on heroin! Does this mean that we will ever become addicted to the chemical substances of our own brain?

The use of opiates in medicine

Mainly in medicine, opiates are used because of their analgesic effect. As noted above, opiates have been used for this purpose for centuries, and to this day they remain the most powerful and selectively effective anesthetics known to medicine. Unlike anesthetic drugs such as depressants, analgesics-opiates anesthetize without impairment of consciousness. After taking a moderate dose of opiates, patients remain conscious and are still able to talk about pain, but no longer suffer from pain.

Another class of substances that has a similar analgesic effect are such common painkillers: aspirin, acetaminophen and ibuprofen. Table 9-1 shows the main opiates used as painkillers along with their effectiveness and duration of activity. As noted, the effectiveness of the drug is the dose required for the desired effect. In Table 9-1, the strength of a drug is expressed in terms of the amount of effective doses of morphine. For example, the effectiveness of heroin is indicated by the number 4. This means that if 8 mg of morphine is required for pain relief, then heroin will need only 2 mg. In other words, heroin is 4 times stronger than morphine. Morphine is a prototype of opiate analgesics and is used as a unit for measuring the effectiveness of other drugs. It is used mainly for very severe pain. Although heroin is much stronger than morphine, it is not used for medical purposes in the United States, because is included in the N1 Drug Group (see Appendix N1) Table 9-1 Characteristics of the main opiates Common name Trademark Effectiveness Duration (in hours) Morphine 1 4-5 Heroin 4 3-4 Hydromorphone Dilaudid 5 4-5 Codeine 0.1 4-6 Oxycodone Percodan 0-75 4-5 Methadone Dolophine 1 24-48 Mepredin Demerol 0-1 2-4 Propoxyphene Darvon 0-5 6 Fentanyl Sublimaze 80 1-3 Pentazocin Talwin 0-2 2-3

When the pain is not so strong, you can use drugs that are less effective than morphine. These are codeine, propoxifen (Darvon), oxycadone (Percodan) and pentazocine (Talwin), which are often prescribed for pain relief. In conclusion, we note that there are opiates that are more effective than heroin: for example, fentanyl, which is more effective than morphine 80 times. Fentanyl is mainly used for anesthesia. In general, opiates are the most powerful and effective pain medication known to medicine. Restrictions in their use as analgesics, occurs mainly due to their ability to induce tolerance and dependence. Tolerance and dependence are caused by the use of all these drugs, although it seems that some, for example, pentazocine (Talwin) cause these effects to a lesser extent. It is hoped that safer analgesics will be invented after endorphins have been better studied and their ability to cause natural pain relief.

Opioids are used in medicine and for other purposes. For example, opiates cause constipation, which can be a problem for drug addicts. Therefore, it is advisable to use them in the treatment of diarrhea. Opioids are still used to treat cough. Basically, dextromethorphan is used for this purpose, which is a synthetic opiate that does not have an analgesic effect and does not cause dependence, but is very effective in suppressing cough. The last medical use of opiates, such as methadone, is to use them to treat heroin addiction.

Psychological and physiological exacerbations

In addition to the analgesic effect of opiates, there are several other actions that they have on the body. The effects of opiates are euphoria, including drowsiness, warmth in the body, heaviness in the limbs. William Burroughs described these feelings in his autobiographical novel “The Addict”: “Morphine first hits the back of the legs, then the back of the neck, the rolling wave of relaxation separates the muscles from the bones so that it feels like you are spreading out, lying in warm saline water “. The pleasure of using opiates seems to harm the other interests of the addict. Burroughs describes it in this way: “A drug addict abruptly gives up sex. The path to non-sexual sociability begins at the same place where sex begins. When I get into the habit of thrashing with G (eeroin) or M (orfin), I become uncommunicative. If someone wants to talk Okay. But there’s no wish to meet someone. ” There is evidence that the use of opiates reduces sexuality, and men are often threatened with impotence. Laboratory studies also show that opiates are detrimental to human social relations.

In terms of physiological effects, opiates are somewhat similar to antidepressants, but there are a few differences. Like depressants, opiates cause breath-holding and lower body temperature, but the effects of opiates on the heart are more complex. Nausea and vomiting often follow immediately after taking antidepressants. Perhaps the most visible sign of opiate use is a narrowing of the pupil. This is such a typical symptom that it is used in the diagnosis of opiate poisoning. In case of death from overdose, respiratory failure is the immediate cause of death. However, the lethal dose of heroin is surprisingly large.

Most victims of overdose, as it turned out at the autopsy, injected the drug less than is necessary for death. Many of these cases included not just an excess of a dose of heroin, but a combination of its use with alcohol or depressants. Opioids and depressants reinforce each other’s actions. Most of the deadly “heroin” overdoses involve this kind of interaction, for example, this was the case with Janis Joplin’s death in 1970:A liter bottle of Southern Comfort whiskey, which she held over her head, was both a symbol of the severity of her life and a way of liberation. When she dried the bottle, she became happier and more radiant, more bizarre … Last week, on a day that seemed less lonely than everyone else, Janice Joplin died on the lowest and sadest note. Returning to her room at the Hollywood motel after working late in the recording studio, having a good drink with friends in a nearby bar, she filled a syringe with heroin and inserted a needle into her left hand. An injection killed her.

Consequences of chronic opiate use

Consequences of chronic opiate use

If opiates are consumed continuously, their effects are somewhat different. As noted, opiates cause tolerance, so if you do not increase the dose, their effect decreases, which often happens. Chart 9-1 data show examples of the effects of opiates on humans and monkeys in the laboratory with continued drug use. Both graphs show daily drug use during the course of the experiment. Data relating to people was obtained through an experiment in which volunteers with extensive experience using drugs were tested in the laboratory and could regulate their own doses. Note the increase in the dose of the drug chosen by the subject each time. In the first month, the subject did not need more than 500 mg per day. By the fourth month, he was taking more than 1000 mg per day. Also pay attention to the bottom of the chart, which demonstrates similar behavior in monkeys that could receive heroin intravenously by pressing a lever. It can be seen that heroin addiction is a universal phenomenon.

Opiate use patterns may change over time. While initially re-use is motivated by the desire to re-experience the pleasant sensations, “tightly seated” drug addicts argue that the drug does not even bring them much satisfaction as before. However, they continue to use the drug in order to avoid unpleasant withdrawal symptoms (“withdrawal”). Thus, heroin use is motivated first by positive and then negative reinforcement. Symptoms of heroin addiction make themselves felt after one to two weeks of using heroin, morphine or synthetic opioid. These symptoms become more severe with prolonged use of large doses. The first symptoms appear 8–12 hours after taking the last dose and include runny nose, tears, sweating, irritability and tremors. Over time, these symptoms become more severe, others appear – pupil dilation, anorexia, and tumors appear. These symptoms continue to intensify and peak between 48–72 hours. At this time, the heartbeat quickens and blood pressure rises, and severe symptoms appear: nausea, diarrhea, sneezing, excessive sweating and bone pain. In addition, the addict can begin spasmodic movements of the arms and legs. Other strange symptoms that are associated with the addict’s sexuality are involuntary erection and ejaculation in men and orgasm in women. The loss of fluid and the reluctance of the addict to eat can physically and emotionally drain the addict and are often fatal.

It is quite simple to rid the addict of withdrawal symptoms and regain his well-being with a suitable dose of any kind of opioid. Inpatient detoxification is the treatment of withdrawal syndromes with low doses of synthetic opiates, for example, methadone. The dose of methadone is sufficient to reduce the severity of withdrawal symptoms, but it is not capable of anything more. Gradually, within a few weeks, the methadone dose is reduced, until the addict is completely cured of his physiological dependence. If heroin continued to be taken solely to relieve withdrawal symptoms, detoxification would be sufficient for treatment. However, after detoxification procedures, the established rate of re-use of the drug is 90% within two years after discharge from the hospital. Most of these relapses occur within the first 6 months. Thus, if the addict returns to the environment where he or she became addicted, it is highly likely that a relapse will occur, despite the absence of physical withdrawal symptoms.

The fact that addiction to heroin (and other drugs) depends not only on physical abstinence is illustrated by a heroin epidemic that has been prevented. In the early 1970s, when the Vietnam War came to an end, the number of drug addicts among American soldiers exceeded 21%. These soldiers were required to undergo detoxification before returning to the United States, but since the relapse rate is 90%, it was expected that most of them would continue to use heroin on their return. Thus, in the USA they expected a surge of a heroin epidemic. However, subsequent studies have shown that very few relapses occurred (less than 15%). This clearly showed that addiction and psychosocial factors associated with Vietnam largely contributed to the development of addiction. Returning to the United States, veterans of the Vietnam War found that heroin became less available. This circumstance, as well as a change in lifestyle and social environment, eased the pressure that initially led them to addiction. However, radical changes in the environment (from Vietnam to the USA) cannot be repeated in the usual treatment. This is one of the reasons for the difficulty of treating heroin addiction, despite the presence of various treatments. Graphsto 9-1 Similar examples of the use of opiates by humans and monkeys in the conditions of constant availability of the drug. Both graphs show the amount of drugs taken for a specific time. Data concerning a person is obtained on the basis of an experiment in which a volunteer with drug use experience consumed them without restriction. Data relating to animals are taken from an experiment in which monkeys who wish to receive a dose of heroin pressed a lever to receive an intravenous injection of heroin.