Cocaine: Where It Comes From and Its Neurological Effects

To people all over the world cocaine is viewed as a taboo drug. It is the cause of addiction and death among other things, but is, nonetheless, used by people of all social classes. Models and celebrities make it seem glamorous but those who have been sucked in by cocaine’s addictive properties or have seen a loved one hit rock bottom because of it know that it can ruin lives. It seems as though something this detrimental could only be manufactured by humans, but is it? Where on Earth does this horribly addictive drug come from? Is there more than one form of ingestion? How does it integrate itself into and react with our brains? And finally, what makes it so great that one would want to use it again and again, even to a point where it is life-threatening?

Cocaine is classified as a psychomotor stimulant. It is found in Erythroxylon coca, which is a shrub native to South America, particularly Columbia, Peru, and Bolivia. Inhabitants of these regions have been using coca (and its various forms) for at least 2,000 years. In the late 1850s, German chemists isolated pure cocaine. Once the drug was introduced to the United States, its popularity grew throughout the late 1800s and early 1900s. In 1914, Congress not only prohibited the use of cocaine in patent medicines, but also specified other restrictions on its import and sale. Subsequently, other state and federal laws were created to further regulate the distribution of cocaine; it is now illegal to posses or sell the drug in America.

Cocaine can be found in five different forms, and routes of administration vary according to each. One natural form is the coca leaf. To feel the effects of the stimulant, one can either roll the leaves into cigarettes and smoke them or infuse the leaves with a liquid to form a kind of tea. Coca paste is another natural form of the drug. The only real option for those who use the paste is to burn it and then inhale the smoke. This paste can be dissolved with hydrochloric acid to synthesize powder cocaine, which is the purest, most widely used form of the drug. Cocaine HCl is water soluble, enabling oral ingestion. It can be used intranasally (snorting) and by intravenous injection. The fourth form of cocaine is a cocaine base, which is a product of cocaine HCl. This form can be made by freeing the cocaine alkaloid from the salt substrate. The base is then smoked, thus constituting the term “freebasing”. Because it is difficult to smoke the base, as it is highly explosive, another form was constructed. The final form involves dissolving cocaine HCl, mixing it with baking soda, heating it, and then drying it to produce “crack”.

The different routes of cocaine administration yield somewhat different levels of plasma cocaine. The rate of absorption (into the body) depends on the amount of blood flow to the site of administration. The more blood present at the area of administration, the faster the drug will be absorbed. Cocaine is absorbed most quickly through smoking and intravenous injection. It can be snorted and absorbed through nasal mucosa as well, but absorption is slower and yields a lower concentration of cocaine in the body. Oral ingestion can be compared to intranasal administration in that it is absorbed much more slowly than smoking or IV injection, thus yielding lower levels of plasma cocaine. The faster the drug is absorbed, the greater the concentration and “high” one feels from cocaine. The drug has a half-life of 0.5 to 1.5 hours.

Cocaine achieves its psychological effects by blocking the reuptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in the brain. Once the drug has been introduced into the bloodstream it must pass through the blood-brain barrier to be effective. The blood-brain barrier is a semi-permeable barrier between the blood and brain that consists of the cells in the walls of the brain’s capillaries. This barrier exists because many substances found in blood fluctuate and would have a disruptive effect on brain cell activity (if the substances were allowed to transfer freely between the brain and blood). The barrier’s selective permeability means that it does not impede lipid-soluble (or fat-soluble) molecules, but it does reduce the diffusion of ionized, or water-soluble, molecules. Cocaine is sufficiently fat-soluble that is passes readily through the blood-brain barrier.

The three monoamine neurotransmitters that cocaine effects are cleared from the synaptic cleft by membrane proteins called transporters. Cocaine binds most strongly to serotonin transporters (SERT), followed by dopamine transporters (DAT), and finally the norepinephrine transporter (NET). The drug acts as a reuptake inhibitor and binds to each of these transporters. When it binds to the transporters, it inhibits their ability to move the neurotransmitters from the synaptic cleft. Because the neurotransmitters are not recycled at a regular rate, their levels in the synaptic cleft increase. Though cocaine blocks the reuptake of norepinephrine, serotonin, and dopamine, it is the dopamine reuptake blockade that seems to account for most of the drug’s reinforcing, stimulating effects. Cocaine activates the mesolimbic system, which is a system of dopaminergic neurons originating in the ventral tegmental area (VTA) and terminating in the nucleus accumbens, amygdala, and hippocampus. The nucleus accumbens plays a particularly important role in the rewarding effects of certain categories of stimuli (including categories of drugs that people abuse).

Cocaine can also inhibit voltage-gated sodium channels in nerve cell axons. These channels are necessary to generate action potentials. So, cocaine’s ability to stop voltage-gated sodium channels allows it to block nerve signal conduction. Thus, when the drug is applied locally to tissue it can prevent transmission of nerve signals along sensory nerves permitting it to act as a local anesthetic (i.e. it has a numbing effect).

Cocaine is abused for the “rush” is produces. Feelings associated with this “rush” are euphoria, a sense of well being, exhilaration, heightened energy, inflated self-esteem, talkativeness and diminished fatigue. The drug can also induce irritability, anxiety, verbal aggression and restlessness. When a user “crashes” or comes down from cocaine, he or she feels withdrawal symptoms, which include depression, increased appetite, fatigue, and dysphoric mood. The “crash” occurs because after the initial “high” normal levels of dopamine are undershot, because neurons run out of dopamine neurotransmitters. The receptors for dopamine then disappear as a response mechanism to the high availability of the neurotransmitter. This contributes to the user’s tolerance and need for a larger dose of the drug to maintain his or her “high”. It is this “high” that causes people to come back for more of the drug, regardless of the fact that it is not good for our bodies.

Because cocaine is a central nervous system stimulant it produces physiological effects too. The most common side effects include increased heart rate, vasoconstriction, hypertension, and hypothermia. High doses of cocaine can lead to death due to the drug’s ability to induce seizures, respiratory failure, heart failure, stroke, and intracranial hemorrhaging.

Evidence has also indicated that cocaine has adverse long-term effects on the brain. Cocaine can decrease the number of dopamine transporters in the caudate nucleus and putamen, which suggests that the overall number of dopaminergic terminals in these regions is diminished. As a result, the probability of Parkinson’s disease increases as people who have abused the drug get older.

SOURCES

Meyer, J. & Quenzer, L. (2005). Psychopharmacology: Drugs, the Brain and Behavior. Massachusetts: Sinauer Associates Inc.

http://www.questia.com/PM.qst?a=o&d=90945986

http://cocaine.org/adminroute/index.html

http://cocaine.org/process.html

http://www2.truman.edu/~marc/webpages/andean2k/cocaine/cocaine.html

http://www.sciencedaily.com/releases/1999/04/990427045818.htm