Converted, or “designer” drugs – synthetic substances obtained by a slight change in the chemical structure of an already known drug. If the drug retains its ability to act on the receptors, it will still have the desired effect, but it will not be prohibited by law. In other words, a specialist chemist can slightly change the heroin molecule and get a new drug with the same properties. And to pursue the spread of this new compound will be impossible under the law. (However, in 1986, a law was passed in the United States that changed this state of affairs.) Converted drugs reduce the risk of selling them, but not when they are used.

Not so long ago in California, an underground chemical laboratory began producing converted heroin, the so-called MRRR. Due to improper manufacturing technology,instead of heroin MPPP, the toxic substance MPMP was obtained. It turned out after several young drug addicts were hospitalized with complete paralysis. At first, the cause of this epidemic of paralysis was a complete mystery. The symptoms strongly resembled Parkinson’s disease. But only older people are affected. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.But only older people are affected. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.But this disease affects only older people. Solve the problem helped the ingenious guess of a doctor named William Langston. He used the drug L-DOPA to treat paralyzed drug addicts. Its use has returned patients at least the ability to talk. After that it turned out that they were the victims of the unfortunate altered heroin.

Studies have shown that MRTR acts selectively, and the main substance of its impact is the black substance. It causes its rapid destruction, and this loss is almost irretrievable. However, the treatment of victims of MRTR showed that the L-DOPA preparation is able to restore some of the black substance cells.
It is necessary to remember two important circumstances. Firstly, the great danger associated with the use of recast drugs is obvious. Since they are not tested on animals and not investigated in the laboratories of medical centers, the person using them is at great risk. Secondly, there may be no obvious symptoms of brain damage. Many people who have taken MRTR only once or twice in their lives do not have any symptoms of Parkinson’s disease. However, the partial destruction of the black substance probably happened. In the process of aging of the body, its cells will collapse further, and this increases the risk that such people will pay for Parkinson’s disease with a single dose of MRTP.

Thalamus and Hypothalamus. From the point of view of studying the effects of drugs, the forebrain, which includes the thalamus, hypothalamus and some other structures, in particular, the cerebral cortex (see Fig. 3-5), is most important for us. The thalamus is often called a relay station, as it receives all the original impulses from the senses and transmits this information to the corresponding parts of the brain. The hypothalamus is the main organ regulating behavior. Obviously, its different parts are responsible for food, drink, body temperature, aggression and sexual behavior. To determine the exact purpose of a particular part of the brain is very difficult, and sometimes we get conflicting data. The main ways to study parts of the brain are damage and stimulation. In a surgical way, some part of the brain of the experimental animal is damaged. After the animal recovers from the operation,there are changes in his behavior that correlate with the damaged part of the brain. For example, damage to one part of the hypothalamus leads to the fact that the animal stops eating, and as a result of the operation in another area, the animal’s appetite is unnaturally increased, which even leads to obesity. Thus, we see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effectwe see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effectwe see that in the hypothalamus there are at least two areas responsible for eating: one regulates the feeling of fullness, the other – the feeling of hunger. Electrical stimulation of areas of the brain, as a rule, has the opposite effect damage.

Damage or stimulation of certain parts of the brain also extends beyond them, so that exposure can affect entire transmission channels of nerve impulses. Therefore, it is better to speak not about the centers of hunger, but about the channels of transmission of the corresponding impulses. However, even this approach can be simplified, because some researchers have noticed that not only information about hunger can be transmitted through such channels. So, they also affect the coordination of movements, taste sensations and much more. But be that as it may, all researchers agree that the hypothalamus plays an important role in controlling hunger, thirst, and other basic sensations.
The center of pleasure in the brain Despite these difficulties, electrical stimulation of brain areas was the basis of one of the most significant discoveries in research on the relationship between the brain, behavior and drugs. In the 1950s, psychologist James Olds worked with the brain of a rat, implanting electrodes in various parts of it and studying the effects of their stimulation. When electrically stimulating certain parts of the brain, the rat seemed to have fun. Here’s how Olds describes his discovery:
When the animal entered a certain corner of the cage, I gave him a short discharge of electric current. But the animal did not run away from the corner, but on the contrary, returned there after a short retreat caused by shock from the first stimulation. After the second stimulation, the retreat period was even shorter. By the time of the third electrical discharge, the rat did not go out of the corner.

Conducting further research, Olds and his colleague Milner found that if the electrodes were implanted in certain areas of the brain, especially in the middle forebrain, the rat could even be trained to press a lever in the cell, including electrocution, some neurons of the middle node go beyond its limits and connect it with the lateral part of the hypothalamus. When the rats learned to stimulate this area, they pressed the lever up to a thousand times per hour. This gave reason to assume that the “pleasure center” is being stimulated. Obviously, this part of the brain is the end point of the channels through which information about the desire for pleasure and its reception passes. Accordingly, to understand the properties of drugs to cause a sense of pleasure, it is necessary to study this area of ​​the brain.One of the main channels of transmission of nerve impulses in the median node is dopamine, so the researchers put forward a version that the main chemical substance associated with the property of drugs to bring pleasure is dopamine. This is supported by the success of the next experiment. The rats learned to press a lever that delivers cocaine through a miniature pipette implanted in the median forebrain. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.implanted in the median forebrain node. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.implanted in the median forebrain node. Thus, people who use cocaine, change the chemical processes occurring in the system of control over pleasure.

The structure of the forebrain includes three more complex organs: the limbic system, the basal ganglia and the cerebral cortex. These bodies form such inherent only to man areas of mental activity, such as memory, logic, speech, planning and reasoning.
Limbic system. These are several organs located inside the forebrain. One of them, amidal, is responsible for certain types of aggression. Another important organ of the limbic system is the hippocampus (seahorse), an important part of the memory system. People with a damaged hippocampus will remember everything that happened to them before the damage, but they are unable to remember new information. Alcohol abuse in combination with poor nutrition leads to a serious mental disorder, known as Korsakov syndrome. In patients suffering from this disease (usually alcoholics from the lower classes of society), there is a memory disorder that is associated with damage to the hippocampus.
Ganglion. One of the causes of Parkinson’s disease is damage to the ganglion, namely the degeneration of a special group of nerve cells, the so-called “black substance”. These cells produce dopamine for the ganglion, and with their degeneration, less and less dopamine is involved in the transmission of nerve impulses. Interestingly, Parkinson’s disease does not occur as long as at least 20% of the substantia nigra cells remain intact.

Cortex. In fig. 3-4 shows the lobes of the cerebral cortex. The occipital lobe is associated with vision and perceives signals from the optic nerve. The temporal lobe plays an important role in the processing of auditory sensations and, apparently, controls the mechanisms of speech. Damage to the left temporal lobe causes a serious impairment of speech ability (at least if the person is right-handed). Damage to the right temporal lobe often affects emotional reactions. In left-handers, the right temporal lobe is responsible for speech, and the left – for emotions. The frontal lobe controls movements and balance, as well as is connected with the emotional and mental sphere and personal characteristics of the character. The parietal lobe analyzes impulses from the organs of touch.

Three important neurotransmitters belonging to the same amino group are called monoamines, norepinephrine (norepinephrine), dopamine and serotonin. Like acetylcholine, norepinephrine was discovered long ago, because it is also located outside the brain. This is the main chemical that regulates the physical changes that accompany emotional recovery. It is also found in the brain and plays the role of a neurotransmitter responsible for the feeling of hunger, wakefulness and waking up from sleep. Serotonin is found in all parts of the brain and plays an important role in regulating sleep. Dopamine is the main neurotransmitter in areas of the brain that provide consistent movements of body parts. This discovery gave rise to the hypothesis that dopamine deficiency can be the main cause of Parkinson’s disease, which affects mainly older people and is characterized by progressive movement inconsistency, hardening of muscles and trembling in the body. In accordance with this hypothesis, new approaches to the treatment of

Parkinson’s disease began to be applied, including the use of the drug L-DOPA, the “initial substance” of dopamine. L-DOPA was prescribed to patients to restore the level of dopamine in the tissues, and gave amazing results. Acceptance of dopamine itself is ineffective, since it cannot get into the brain along with blood. The brain is protected from toxic substances by the blood filtration system or the blood barrier of the brain (encephalogen barrier), which also detains dopamine. But L-Dofa overcomes this barrier and, getting into the brain, turns into dopamine. The use of L-Dov in the treatment of Parkinson’s disease is a vivid example of the value of scientific studies of neurotransmitters. Although L-Dova does not eliminate the disease at all (the loss of dopaminergic neurons continues, and even this drug cannot completely fill it), it prolongs the life of people with Parkinson’s disease, who would have died many years earlier without it.

In addition to these functions, monoamines are closely related to mood and emotional disorders. The discovery of substances affecting monoamines has revolutionized psychiatry. There is strong evidence that severe clinical cases of depression are associated with biological disorders. According to the latest theories, clinical depression occurs due to changes in the level of monoamines, especially norepinephrine and serotonin. This is also confirmed by the fact that drugs destroying monoamines cause depression. As we have said, reserpine causes leakage in the vesicles of nerve endings and the subsequent destruction of neurotransmitters, as a result of which there is a shortage of monoamines in the body. Drugs used in the treatment of depression significantly increase the production of norepinephrine and serotonin.

Monoamines, and especially dopamine, also constitute the biochemical basis for the occurrence of another serious mental illness, schizophrenia. When it happens, there is an almost complete loss of connection with reality, manifested in deceptions of feelings, hallucinations, disturbed emotional reactions and falling out of public relations. It is proved that these symptoms are caused by increased activity of monoamines. First, all drugs used to treat schizophrenia block monoamines. There is a very close relationship between the strength of the therapeutic effect of the drug and its ability to block dopamine receptors. In addition, compounds incapable of this, as a rule, do not relieve the symptoms of schizophrenia, even if they possess all the other properties inherent in effective drugs. Another interesting piece of evidence: stimulant drugs such as cocaine and amphetamines increase dopaminergic brain activity. Although small or moderate doses of these stimulants improve mood, overdosing often leads to paranoid disorders and loss of connection with reality, which almost exactly repeats the symptoms of schizophrenia. When the effect of the drug diminishes and dopaminergic activity returns to normal, these symptoms disappear. This again indicates a connection between increased dopaminergic activity and schizophrenia.

Of all the neurotransmitters, acetylcholine was one of the first to be discovered, possibly because it is located in the most convenient neurons for studying, located outside the brain. It is contained in the endings of the neurons that control the muscles of the skeleton. At the junctions of the nerves with the muscles, there is a space similar to a synapse, which is called a neuromuscular junction. When neurons connected to muscle fibers are excited, they release acetylcholine to the neuromuscular junction area, and the muscles contract. Acetylcholine also plays an important role in the brain, but like most other neurotransmitters, its function is not fully understood. Nevertheless, it is known that he is an important regulator of thirst. In the formation of adjectives from a neurotransmitter, the root of the word is simply taken (in this case, choline) and the suffix “ergic” is added to it. So, we call thirst cholinergic function, acetylcholine-containing neurons — cholinergic neurons, and drugs that block acetylcholine — anticholinergic drugs. Presumably, acetylcholine is also an important element of the memory system.

There is evidence that Alzheimer’s disease – progressive memory loss in old age – is associated with impaired functioning of neurons in one of the cholinergic sites. The most recent studies of Alzheimer’s disease are aimed at determining the nature of damage to these areas and developing methods for treating or preventing these injuries. In 1993, the Park-Davis Commission announced that it had received and officially approved the first drug for the treatment of Alzheimer’s disease, takrin (Sodpech), which increases the level of acetylcholine in the brain tissue. Studies of Alzheimer’s disease have provided new evidence that the cause of mental illness is a disruption in the normal functioning of neurotransmitters.

There are many ways in which drugs can interfere with impulse transmission. Suppose that the chemical structure of a drug is very similar to the structure of a neurotransmitter in the body. If the degree of similarity is great, then the drug molecules will bind to the receptors and “deceive” the neuron, causing it to react in the same way as a real mediator. This is how many drugs work (this is called mimicry). For example, morphine and heroin exert their effects due to their similarity with the recently discovered endorphin.

The narcotic effect is produced by changing the following neurochemical systems:

1. Synthesis of neurotransmitter. Drug increases or decreases the amount of neurotransmitters produced.
2. Neurotransmitter transport. The drug interferes with the delivery of neurotransmitter molecules to the nerve endings.
3. The accumulation of neurotransmitter. The drug interferes with the accumulation of neurotransmitter in the vesicles of nerve endings
4. Isolation of the neurotransmitter. The drug causes premature release of neurotransmitter molecules into the synapse.
5. Disintegration of the neurotransmitter. The drug affects the breakdown of the neurotransmitter through enzymes.
6. Reverse neurotransmitter uptake. The drug blocks the reverse absorption of the neurotransmitter into the nerve endings.
7. Activation of the receptor. The drug activates the receptor through mimicry.
8. Lock receptor The drug makes the receptor inert, blocking it.

In addition to mimicry, drugs can affect the transmission of nerve impulses in many other ways. Models of the mechanisms of this influence are shown in Table 3-1. Neurotransmitters are produced from less complex compounds, the so-called “source molecules.” The production of mediators usually occurs in the cellular body or nerve endings, and if this process goes on in the cellular body, then before the mediator can work, it must also be transported to the nerve ending. Some drugs interfere with the production or delivery of a mediator. Neurotransmitter molecules accumulate in small containers (bubbles) along the edges of nerve endings. Some drugs affect the ability of bubbles to accumulate the necessary substances. For example, under the influence of a drug, reserpine, which was once used to treat high pressure, leaks appear in the bubbles, and the neurotransmitters contained in them cannot reach the synapse in the right amount in time. Other drugs have the opposite effect, increasing the flow of mediators into the synapse.

This is how stimulants act, such as amphetamines. 

Another important feature of the transmission of nerve impulses is that the neurotransmitters should be deactivated after exposure. A neuron can be compared with a rechargeable electric battery: after excitation, it needs recharging. But it begins after the keys are taken out of the locks. Deactivation of the neurotransmitter can be done in two ways: by fermentation (destruction by enzymes) and reverse absorption. Enzymes are special compounds responsible both for the production of neurotransmitters and for their destruction to the state of inert substances. These are very complex processes. There are many chemicals in the brain tissue, and they are constantly changing their structure. Consider the production and destruction of acetylcholine, one of the most important neurotransmitters. To obtain it, the enzyme acetyltransferase reacts with the “original” choline molecule. As a result of the destruction of acetylcholine, for which another enzyme, acetylcholinesterase, is needed, two metabolites, choline and acetate, are formed. (The names of enzymes necessarily contain the roots of the names of the substances with which the enzyme reacts, as well as the ending – ase.) The drug can interfere with the process of impulse transmission, affecting the enzyme. For example, some antidepressants interfere with the deactivation of the neurotransmitters norepinephrine, dopamine and serotonin, weakening the effect of monoamine oxidase, an enzyme that destroys these compounds.

The second way to remove neurotransmitters from the synapse is reverse absorption. Neurotransmitters return back to the nerve ending from which they were isolated. Such a decontamination process is more economical, since the neurotransmitter molecule remains intact and can be used again without spending energy on the development of new ones. Some drugs (especially cocaine and amphetamines) have one of their actions, blocking the process.

The last group of drug actions is directly on the receptor. Some drugs affect the receptor, posing as a real neurotransmitter (a kind of duplicate key that fits the lock). Other drugs wedge the lock and prevent the neuron from exciting. They are called blockers. In general, any substances, endogenous or not, that approach the receptor lock and activate the neuron, are called the protagonists of this receptor. Any compound that does not activate the neuron itself and prevents other substances from doing this is called an antagonist. For example, naloxone is an antagonist of receptors that are affected by opiates like heroin. If you give naloxone to a person who has just taken a lethal dose of heroin, he will not only not die, but will even come to such a state as if he had not taken the drug.

In general, naloxone completely blocks and repeals all effects of heroin and other opiates. Therefore, naloxone is called an opiate antagonist. It should be remembered that although drugs interact with brain tissue very differently, the mechanism of this interaction always contains processes characteristic of the normal functioning of the body. The drug activates or slows down the functioning of certain parts of the brain with certain natural functions. Differences in the action of different drugs can be explained by examining which neurotransmitters they influence and how. Therefore, it is necessary to consider the neurotransmitter systems of the human brain and some of their known functions.

At the ends of the axon are small thickenings – nerve endings. In them lies the answer to the question of how electrical impulses are transmitted from one neuron to another. When the microscopes were created, which made it possible to clearly see the neurons, an amazing thing came to light: most of the endings of one neuron do not come into close contact with the dendrites of the next, as it has been assumed so far.

The space that separates them is called a synapse (shown in Figure 3-2). Of course, the question arises, how is the electric current conducted from one neuron to another, if they do not touch? It is now known that when the current reaches the nerve ending, the chemicals (neurotransmitters) in it are released into the synapse, and it is they who activate the adjacent neuron.

Thus, the transmission of nerve impulses is an electrochemical process: electric, as long as current flows along an axon, and chemical at the synapse. This is important, since it can be assumed that drugs act on the nervous system through the synapse, because here there are chemical processes of information transfer. Indeed, most psychoactive substances produce their main effect through the synapse. Therefore, it is appropriate to consider in detail the chemical processes occurring in the synapse.

To describe the process of transmission of nerve impulses, we use the analogy with the key and lock. Special endings are scattered across the entire surface of the dendrites and the cell body – receptors. They can be compared with locks that protect the neuron from excitation. For excitation, you need to open the locks, and this is done by neurotransmitters released into the synapse. Molecules of neurotransmitters – the keys. The mechanism for opening the lock is shown in Figure 3-2. Receptors are depicted as circular depressions on the surface of the dendrite, neurotransmitters – balls released from the nerve ending. The idea is simple – in order to trigger the nerve impulse transmission mechanism, the key must go to the lock.
In fact, neurotransmitter molecules and receptors have a much more complex chemical structure than can be seen from the figure, and the analogy with the key and lock does not fully explain the process. The mediators and their receptors are electrically charged, and therefore attract each other, and when the mediator key enters the receptor lock, they bind. When a mediator molecule enters the receptor in a neuron, a reaction occurs causing its excitation. It is important to note that there are many types of neurotransmitters and their corresponding receptors. In brain tissue, there are chemically encoded paths along which various neurotransmitters move.

The simplest components of the nervous system are cells called neurons. They are in many ways similar to other cells of the human body, such as blood cells or muscle cells, but they have a unique feature – they can communicate with each other. To understand the nature of the process of transmission of nerve impulses need to consider the unique structural properties of neurons. From Figure 3-1 it can be seen that there are cellular bodies in a neuron that are similar to the bodies of any other cells. Among them is the nucleus containing the genetic information for a given neuron and controlling the metabolic processes in the cell. Several related formations, called dendrites, and one long cylindrical formation, the axon, depart from the neuron cell body. Such formations have only a neuron, and their specific functions are associated with them.

Axons are of different lengths, but in any case they are longer than shown in the figure, sometimes several thousand times longer than the diameter of the cell body. The axon is covered with a white fat coat called myelin. (Not all axons are covered with such a shell, and the “open” ones are gray). Myelin can be compared to electrical wire insulation. This is a suitable comparison, since the main function of the axon is to transmit electrical current. Axon transmits information by transferring electrical charge from one end of the neuron to the other. The current is always transmitted from the cell body, which sends an electrical impulse to small branches at the end of the axon. The difference in potential is small (about 110 millivolts). When an axon conducts a current, it is called excited, when not – in a state of rest.

Any of our feelings or emotions – in essence, any psychological sensation – is based on brain activity. The fact that the brain, this physical entity, is the basis of mental activity, gives us the key to understanding the mechanism of action of chemically active substances (drugs) on mental processes.
All psychoactive substances produce their effect by acting in different ways on the tissues of the nervous system, and this chapter is devoted to such physiological effects of drugs. Most of these effects occur at the level of the brain.Recently, many significant discoveries have been made in the sciences that study the brain, shedding light on the mechanisms of the functioning of the brain. In parallel with these successes, our ability to study the effects of drugs on the body is increasing. There were fundamentally new approaches to solving problems such as addiction to drugs. However, before discussing the effect of drugs on the brain, one should consider the basic principles of the brain.