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.