MikailaKononchik

Cocaine Production and its Pathway Through the Body The Erythroxylum coca plant, common to the Andes in South America, is one of the oldest natural stimulants, dating back to 3000BC. It was used by Incas as a way to counter the effects of thin mountain air. It was effective in this because it increased heart rate and breathing as well as curing stomach pains. In 1859 Albert Nieman, a German chemist, discovered that a substance could be extracted from the leaves and used to give the same effects. This substance was cocaine. In the late 1880s this extract was introduced to the medical world as an anesthetic during surgeries. Sigmund Freud, in particular, took a great interest in this new medicinal drug and discovered it could be used as a cure for depression and erectile dysfunction as well as a painkiller. Freud’s discovery led to the first documented case of addiction, in Dr. Halsted. While testing the theory of cocaine as a painkiller, he injected himself multiple times and discovered that it numbed the nerves. However, his testing of cocaine’s effects left him with an addiction so crippling he could not perform his duties as a doctor for close to a year. The addictive factor of cocaine was overlooked because, at the time, cocaine was being marketed as a miracle cure-all drug. By 1970 cocaine had been made illegal for any use except as an anesthetic for very specific surgeries. Despite being made illegal, cocaine is still commonly used as a recreational drug and is the most powerful drug from natural origins. As of 2012 one out of every 40 adults has tried cocaine and users are most commonly found between the ages of 18 and 25. According to the 2012 World Drug Report it is one of the top five most popular drugs.1 As popular as cocaine is, there are still numerous dangers to using it. Once cocaine has been made and administered to the body, it leads to harmful side effects, addiction, withdrawal and, in many cases, relapse.

The international nonproprietary name for cocaine is benzoyl-methyl-ecgonine and it contains a hydrophilic group joined to a lipophilic group by an aliphatic group.2 The process for creating cocaine is dependent upon which form the creator wants—the “base” or the hydrochloric salt. The base form, which has a rocklike appearance, contains all forms that have not been neutralized by an acid. The hydrochloric salt takes the form of a powder. To create the hydrochloric salt, the coca leaves are first turned into a paste. This is accomplished by adding water, an organic solvent, and some alkaline material to powdered coca leaves and shaking the mixture. Once the water and leaves have been removed from the mixture, an acid is added. The acid will remove any left over solvents from the mixture. Baking soda is added to the mixture as it dries into “coca paste”. This paste is dissolved in hydrochloric acid and water. Adding potassium salt to this mixture will cause a separation of the substances and the cocaine can be precipitated from it by adding ammonia. Once the precipitated cocaine has dried, the hydrochloric salt form, called cocaine hydrochloride, has been made.3 The base form of cocaine can be produced through two different techniques producing what is called “freebase” and “crack”. Freebase is created when a base (such as ammonia) and a solvent are added to a solution of dissolved cocaine hydrochloride in water. Ether is usually used as the solvent, which dissolves the cocaine and allows it to be extracted through evaporation.4 The process for making crack is similar, cocaine hydrochloride is still dissolved in water and a base, either ammonia or sodium bicarbonate, is still added to it, but now the mixture is heated to remove the hydrochloride and leaves a soft product that hardens as it dries.5 While freebase and crack are made from differing techniques, the chemical structure remains the same.

The primary methods of getting cocaine into the body are through smoking, injections or insufflation, referred to as snorting. Powdered cocaine, the hydrochloric salt form, can not be smoked. The covalent bonds holding the salt of the powdered cocaine together are very strong because of the attraction between the opposing charges of the ions. The heat required to break these bonds and turn the substance into a vapor suitable for smoking is about 180°C.6 This temperature causes instability in the cocaine through decomposition and burning. Crack cocaine can be smoked because of its lower melting point—about 80 °C.780 °C is not a high enough temperature to decompose or burn the cocaine, so users are able to smoke it without the “high” being dampened. The salt in the powdered cocaine, which prevents it from being smoked, is what makes the molecule hydrophilic. The negative charge contained in the salt makes the compound polar and allows it to be dissolved in other polar substances, like water. Once it has been dissolved in the water, this solution can be injected through the bloodstream. Unlike powdered cocaine, crack cocaine is not soluble in water because it is nonpolar. Adding a hydrogen to the crack cocaine makes it an ion and allows it to dissolve. Lemon juice is typically used to dissolve crack cocaine because of its acidity.7 The time taken for the user to feel high depends on the method of absorption into the body. Snorted and smoked cocaine takes 3-5 minutes8, injected cocaine only takes 15-30 seconds.9The discrepancies between the different methods are due to the amount of time it takes for the cocaine to reach the brain.

Once in the body, cocaine travels to the ventral tegmental area of the brain. This is the area of the brain contains the body’s pleasure response mechanism. When pleasurable activities are undergone, the nervous system releases the chemical messenger, dopamine, as a reward. The dopamine travels across the synapses and binds to a receptor on an adjacent neuron sending a signal to produce a “pleasant feeling”. After this happens, the dopamine transporter assists with the reabsorption of dopamine.10 The transporter binds the dopamine and sends it from the synaptic cleft into a neuron. Once in the neuron it is absorbed into a storage vesicle. When cocaine enters the ventral tegmental area it binds to the dopamine transporter and interferes with reabsorption by preventing hydrogen bonding. This causes the dopamine to continuously release into the synaptic cleft and keep producing the pleasant feeling, which is known as the “high”.10,11 Norepinephrine is the neurotransmitter responsible for regulating sleep cycles, attention, focus, and memory. One of the chemicals used in the production of the adrenaline hormone is norepinephrine. This accounts for the excess energy cocaine gives users. Similarly to its affects on dopamine, cocaine binds to the receptors, which begin the reabsorption mechanism for norepinephrine. Though cocaine does not stimulate production of norepinephrine, because there is less reabsorption, a buildup still occurs. This buildup causes a chemical imbalance, which causes the variation in sleep cycles and attention, as well as memory loss.12 Serotonin is the neurotransmitter involved in the regulation of appetite, emotions, and memory. Cocaine slightly resembles the structure of serotonin, allowing it to bind to the receptors. Once bound, the cocaine can stop the release of serotonin and reduce the amount produced. Serotonin deficiencies cause anxiety, depression, and even violent behavior.13 After the elation of cocaine wears off, these feelings only increase. Though getting high is the primary effect of the drug, because cocaine travels via the bloodstream, it has an effect on the entire body. Blood vessels contain an inner layer called the endothelium. Endothelium controls blood pressure through constriction and dilation as well as forming blot clots. The endothelium releases endothelin, which causes the constriction and blood clots. Cocaine interacts with receptors to release excessive amounts of endothelin causing blood clots in various parts of the body.14 Cocaine constricts the blood vessels in the brain, which causes strokes and seizures. When cocaine reaches the heart it can prompt a heart attack or arrhythmia by constricting the blood supply to the heart and increasing the heart rate and blood pressure. Cocaine prevents oxygen from reaching the stomach by constricting the blood vessels. This leads to ulcers and punctures in stomach and intestines. Cocaine use causes rhabdomyolysis (deterioration of the muscles) through vasoconstriction, which leads to kidney failure. When the endothelin is released, constricting the blood vessels, this increases the blood pressure and can lead to muscle deterioration. Damaged muscles trigger the release of myglobin which is filtered through the kidneys. If too much myoglobin is released, the kidneys clog and eventually fail. Snorting cocaine has adverse effects on the nose and lungs. It can create holes in the nasal passages and permanently damage the lungs.15 The effect of cocaine will wear off anywhere from a half hour to two hours after injection.

Because cocaine simulates the reward centers of the brain, it generates cravings for more cocaine. This addiction causes the body to become tolerant to cocaine and greater amounts are needed to obtain the previous high. When cocaine is used excessively, the body reacts by limiting the amount of dopamine, either by destroying it, making less of it, or simply turning off the receptors16. Eventually the brain becomes dependent on cocaine to stimulate dopamine production. The brain has a reward center to encourage behaviors necessary for survival. When an activity that benefits our survival is carried out, the brain releases dopamine. This pleasant feeling is intended to make the survival activities second nature to humans. When dopamine is released, the brain recognizes that this activity needs to be remembered and repeated. Because cocaine stimulates the receptors to release dopamine, it is noted as an activity that needs to be remembered and repeated and becomes second nature to continuing using cocaine.17 This is what causes the addiction. The addiction to cocaine is more powerful than an addiction to natural stimulators of dopamine release because cocaine stimulates a greater release of cocaine and, as such, produces a stronger “pleasant feeling”. After the high has ended, users can feel more miserable than they did before taking the drug. The reason for this is because dopamine is released at such an accelerated rate, that the brain has to amplify its process for reabsorbing the dopamine. The brain is unaccustomed to having to make this increase that it is unable to regulate the process. After the cocaine wears off and the dopamine is released naturally the brain is still absorbing at a rate concurrent with the production from the cocaine.18 Cannabinoid receptor 1 works to regulate communication between neurons. Cannabinoid receptor 1 relays messages to slow down processes to a portion of the brain known as the nucleus accumbens, which controls emotion and motivation. Cocaine excites the nucleus accumbens, which in turn, slows downs processes at a much faster rate and it continues to slow down processes after the cocaine has stopped exciting it. Going quickly from a high, excited state to the “crash” caused by the nucleus accumbens, is what leaves the user feeling more miserable and causes user to become dependent upon cocaine to feel happy and leads to withdrawal once cocaine use has stopped19,20,21. Typically withdrawal symptoms from cocaine disappear after one or two weeks.

The body rids itself of cocaine through metabolism and excretion. In the chemical structure of cocaine, there are two ester groups: ecgonine methyl ester; these groups get broken down through hydrolysis. When cocaine comes in contact with water, these reactions happen spontaneously. The blood and liver have enzymes that function to speed up this reaction ensuring cocaine does not remain in the bloodstream for extended periods. The liver also converts a portion of cocaine into norocaine, an anesthetic. The liver removes the methyl group from the nitrogen in the hydrolyzed cocaine to form this molecule. The three hydrolyzed forms of cocaine as well as a small amount of unchanged cocaine are excreted from the body via urine. This procedure occurs very rapidly.22,23,24

Because cocaine reworks the brain’s circuitry, it can lead to relapses in persons who are no longer using cocaine. Because cocaine binds to the receptors in the ventral tegmental area it causes cocaine linked cues in this portion of the brain, meaning this is the portion of the brain that switches on whenever there is a craving for it. The ventral tegmental area relays information, via the chemical messenger, dopamine, to the medial prefrontal cortex. After withdrawal, both the ventral tegmental area and the medial prefrontal cortex contain greater amounts of brain-derived neurotrophic factor. Brain-derived neurotrophic factor leads to relapse because it is a main factor in the regulation of synapse structure and function. The brain-derived neurotrophic factor binds to the TrkB receptor on the dopamine neurons in the ventral tegmental area. TrkB regulates its actions by adding molecules of phosphate to tyrosines, which in turn, activate signaling between cells.25 Because the ventral tegmental area contains increased brain-derived neurotrophic factor after withdrawal, the synapses are able to be changed in such a way that cravings for cocaine are present. Another cause for the cravings is cocaine ability to kill serotonin axons. Depressed and anxious feelings only increase when serotonin can not be released. Because the cocaine user is accustomed to remedying these feelings with cocaine, the brain begins to send signals to consume cocaine in order to restore happiness.

Cocaine is considered to be one of the most rapidly growing drug of choice and it side effects far away outweigh the euphoria that comes with getting high. When the cocaine has been neutralized by an acid, cocaine hydrochloride is made. Cocaine that has not been neutralized is either freebase or crack. Then methods for administering cocaine to the body are smoking it, injecting it, or snorting it. All of these methods will eventually get the cocaine into the bloodstream. Regardless of the type of cocaine used or the method for getting it into the body, cocaine cause physical damages as well as mental. Cocaine use causes impulsive behavior, anxiety and violence. When snorted, it can leave holes in the nasal passages. Because cocaine gets into the bloodstream, it travels to every part of the body causing damage through its affect on the blood pressure and vessels. The cocaine causes the blot to clot, as well as narrowing the blood vessels. This action causes the blood pressure to increase dramatically. The blood clots and vasoconstriction are responsible for strokes, seizures, heart attacks, ulcers, muscle deterioration and kidney failure. The high is caused from the release of dopamine, which has it consequences as well. The cocaine can permanently damage the dopamine mechanism, leading to addiction, withdrawal, and in some cases relapse. The body rids itself of the cocaine very rapidly through metabolism and excretion, meaning the high does not last lone. The high that cocaine users so desperately crave, is the reason for their addiction, and this addiction is what causes the increasingly harmful side effects that damage their minds and bodies.

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