General features: The plant earns extreme vile reputation around the world due to its natural ability to synthesize the beleaguered addictive drug, Cocaine. Therefore, everyone views the plant as a source of corruption associated with illegal trading, violence and social disturbances. But aside from these disturbing facts and taking away momentarily the thought of being an adversarial component, one would see that it is actually a miracle plant having mindboggling nutritional and medicinal treasure. Further, it is an essential part of many of the South American nations’ necessary cuisine, integrated in daily life. This contentious plant actually provides important medicinal help to the inhabitants of Andes Mountain, also helping establishing the modern society in Bolivia, Ecuador, Colombia and places in Argentina and Peru. Either by chewing or sipping tea made out of this leaves help them combatting the effect of altitude sickness. The practice, still they continue for survival. It is the very reason, the plant turns to be the cash crop in those regions. It is an absolute necessary component in the life of native Andean people. It earns extreme bad rap for illicit production and smuggling of Cocaine by devious traders. But chewing or sipping tea would generate no addiction. The psycho-active alkaloid, Cocaine exists in a very low level (~ 0.3 – 0.7 % of dry mass). This low level alkaloid content serves as a tonic to the native mountain population helping oxygenate the blood matchlessly, energizing them to perform daily the heavy duty chores. The easy extraction of Cocaine by acid-base procedure creates its quick availability enabling to open a vast market to the rampant users during social recreation that often leads to forever addictiveness. The fact has been well established and evidences are all around. The universally popular American drink Coca-Cola once used to add Coca leaf extract (possibly around1880) which drew enormous popularity to be an invigorating drink. It is now replaced by the extract devoid of Cocaine. Sipping Coca leaf tea or chewing the leaves enhances energy level like caffeine. Besides its unrivalled oxygenation role, leaves are enriched with iron, Vitamins A & B, Riboflavin, Phosphorous and Calcium. Some even claims that reason behind the high longevity of Andean mountain people relies on the Coca leaf use.
The plant belongs to the family of Erythroxylacea, flowering tree family, which is native of the South American regions having 242 species and four genera. Among those one of them is Erythroxylum novogranatense, which is also a Coca plant. But the common variety normally produced is Erythroxylum coca which produces cocaine in high level. The plant looks like a Blackthorn bush. It reaches to the height of 7 – 10 ft. The leaves appear opaque, thin and oval shaped but taper at the end. They are approximately 3 – 4 inches long and 0.5 – 1.0 inch wide. The flowers are small and built with five yellowish white petals. The anthers are heart shaped. The pistils are made of three carpels combined and creating three chamber ovary. When matured, the flowers change to red berries. Experiments established that Coca leaf can cure alcoholic hangover. Chewing leaves before drinking prevents body to absorb excessive alcohol. The practice also provides relief to the sufferers from arthritis or any topical pain including helping the victims of pre-menstrual syndrome (PMS). It is highly beneficial during eye surgery for preventing the eye flinching. The leaves are often used in local culinary purposes in making bread, cookies or chocolates (Kuka Xoco) by mixing with the cocoa beans which is delicious as well as beneficial for the medicinal reasons. The leaves are also often added in salads. Coca leaves have significant beneficial role in health. Despite considerable benefits of the leaves, the US department of Homeland Security along with other Western Nations impose strict ban on Coca leaves to enter the countries. So chefs, scientists and even doctors are not allowed to conduct any research to develop any medicines from it. Even it is a beneficial food but the easy isolation ability of Cocaine keeps the use far away. Its legal boundary exists within few Andean Mountainous nations where it is a cash crop and a necessary food. It is cultivated on the slopes of Andean Mountain. Therefore ~ 98 % of global productions are bordered within the countries like Colombia, Peru, Bolivia and a part of Argentina. Few regions of Argentina and even Mexico also legally grow Coca to a certain extent. As per its cultivation, the seeds are sown within the months of December to January and raised under shades keeping away from the direct sunlight. The plant grows best in damp and hot climate. The average life of best quality plants are ~ 40 yrs. afterward, it would not produce much good quality leaves. So often re-plantations are sought. The major harvest of fresh leaves is conducted in the month of March.
History of Coca use: Historically, the use of Coca leaf within Andean natives has been noticed around ~ 3000 BC which is evidenced from the artifacts and mummies unearthed from pre-Colombian graves. Coca was an important material within pre-Colombian culture. Besides the large trade value as a cash crop, it is used as medicine, aphrodisiac and ritual inebriant. It was also often sacrificed during the auspicious occasions to Gods. The natives believe that Coca sets link between God and human providing them the individual divinity as well. It is burnt as incense, worn for ritual adornment also smoked on that behalf. In normal social gatherings, the Andean natives chew Coca leaves. The practice is still continuing. It is thus a part of the social interaction. The ancient healers often used Coca leaves to retrieve souls of ill people asking help from the God. By offering leaves, they believe that God will bring back the original spirit inside the body of those sufferers. To the ignorant Spanish intruders around ~ 1560 AD in South America, typically, it was a complete voodoo. The Spanish Inquisition declared the native rituals as witchcraft. So out of contempt, they banned and suppressed the use. The natives totally disregard the ban since it is a necessary ingredient for survival at this oxygen poor high mountain region. In recent days, the use of Coca leaves has been legalized among the natives in Peru, Bolivia and several South American nations of the Andean regions. Considering the mythology, Andean Tukano Indians believe that the plant grew out of the finger joint of the daughter of lord of all living creatures. In that accord, all varieties of Coca plants are the siblings, so they should be taken good care. The Tukano males spend about three hours a day to prepare Coca powder which every tribe consumes keeping them productive and subsequently suppressing the hunger. It is their firm belief that Coca protects the body removing away any dark spirit. Seemingly, the plant appeared in the Europe around 1570 – 1580 AD. About two centuries later, the isolation of Cocaine was successfully performed by a German chemist naming Albert Niemann in 1859 AD. At the end of nineteenth century, cigars and cigarettes rolled out of Coca leaves were sweeping all over the Western European nations including the east coast of America. Around 1864, a French chemist, Ange-Francois Mariani / Angelo Mariani produced a sweet wine, ‘Vin Mariani’ using the Coca extract which became highly appreciated throughout the Europe earning awards and accolades from the European elites like, Queen Victoria and even Pope Leo XIII. The wine turned out to be hugely popular that eventually gave birth a galaxy of intellectuals in Europe for example, Alexander Dumas, Henrik Ibsen, Jules Verne, H.G. Wells and Thomas Edison in the US. The famed nineteenth century French intellectual, Octave Mirbeau thought it as the energy from Goddess. Vin Mariani was actually the precursor of Coca-Cola, where extract of Coca leaf was punched with the extract of Kola nuts providing caffeine for being an energy drink. In recent days, adding Coca leaf extract having cocaine is legally prohibited to use in Coca-Cola.
History behind bad rap for coca leaf use: In 1722, Father Antonio Julian, a Jesuit priest of Spain wrote a book “Perla De America” where he mentioned the merits of Coca leaf and recommended highly to all the Europeans as an alternatives to coffee or tea because of the beneficial effects on health. Later around 1793, Spanish physician naming, Don Pedro Rolasco published an article praising the benefits of Coca and recommended it for the Spanish sailors. Long afterward, around nineteenth century by the efforts of German scientists and physicians Coca was highlighted further within the European community due to its invigorating actions enhancing the overall metabolism of body. The isolation of embattled alkaloid, Cocaine in 1859 by Professor Albert Niemann of Gottingen identified the central reason behind the stimulating efficacy of coca leaf. But that did not bring any taint on its reputation for use at that time. On the other hand, isolation of Cocaine became the most delightful saga for the drug titan, Park Davis to seek for a large market. Around 1880, company brought in the market a vast array of health products containing pure Cocaine eg, mouth wash, gargles, candies, tablets, sprays and ointments. The legendary, Sigmund Freud soon became its devotee. He also wrote an article “On Coca” in 1884. Along with its reputation, Coca leaf also gained controversies due to the presence of Cocaine even at very low and harmless level. The existence of other beneficial ingredients like, sizeable reserve of antioxidants, vitamins, calcium and iron was very much willfully ignored. Its tremendous medicinal ability without inflicting any side effects to control blood glucose and preventing ability toward obesity is totally snubbed. In a very shrewd way, an American pharmacist naming Asa Griggs Chandler of Atlanta, Georgia filed a patent in 1891 for a drink naming ‘Coca-Cola’ adding isolated Cocaine from the Coca leaf and a blast of caffeine from Kola nuts. Essentially, he followed the example of Vin Mariani and its popularity. The drink earned huge popularity by hooking up the people all over the US while using the Cocaine. Everyone in the US from physicians to musicians or scientists embraced the drink. Eventually, its popularity soared limitlessly. But in 1906, the company withdrew Cocaine from Coca-Cola due to the imposition of US Government’s restriction against using any Cocaine associated products, while defining it as narcotics. The withdrawal of Cocaine did not end the company’s long tie with Coca leaf. It remains the sole user of Coca leaf extract in the US. Coca-Cola legally owns the forever rights of Coca leaf extract. The extract is now prepared by Stepan Company plant which was previously named Maywood Chemical Works in New Jersey, US. As per agreement all the Coca products will go only to Coca-Cola except the extracted Cocaine which is sold to the chemical firm, Mallinckrodt. Stepan is authorized to make Cocaine free Cola leaf extract only for Coca-Cola. So Coca-Cola is the company within US who only uses the unique flavor of Coca leaf. Clearly, it is a shrewd business tricks to establish monopoly over the use of any products made from the Coca leaf. Without the legal approval of Coca-Cola no one would gain the access to use any products of Coca leaf. It is the only company who is allowed to import any Coca leaf cultivated in Peru under its supervision. In that way, Coca-Cola is the sole authority of Coca leaves in US but not outside. But through heavy lobbying in the US Congress, the US government pressurized other nations through the UN not to cultivate any Coca plant by declaring it as a narcotic. In recent days several South American nations vigorously opposed the act since that plant is a necessary factor for their survival. Due to strong opposition the bans are lifted in some specified places especially in Bolivia where the parliament and its president unanimously opposed it. The president of Bolivia is himself an Andean native and also a Coca farmer. Without the permission of Coca-Cola no Coca leaf could be imported to US even for the purpose of medicinal research. The company is holding its perfect monopoly just by advertising and advocating the adversarial effects of Cocaine.
Popular medicinal use: Coca leaf often is used as an important folk medicine throughout the South American nations especially within the Andean natives to maintain health and fitness. It is widely used even today to treat different types of pain, rheumatism, cold, flu, digestive problems including constipation, colic, upset stomach, exhaustion, altitude sickness, and weakness also for assisting while in the labor. Additionally, the dry leaves are smoked to help bronchitis, cough and asthma sufferers. The tea made out of Coca leaf reduces diabetic problems, suppresses appetite, helping reduce the body weight for obese persons. It provides help due to the altitude and travel sicknesses.
Alkaloid content, chemistry and traditional effects: On an average, Coca leaves contain 0.5 – 2.5 % alkaloid which are mainly Cocaine, Cuscohygrine or Hygrine. In addition to the major ones it synthesizes several others which are Methyl-Ecgonine-cinnamate, Benzoyl-Ecgonine, Truxilline, Hydroxy-tropococaine, Tropococaine and Nicotine. A few are metabolites originated from the cocaine and pharmacologically inactive. Regarding the chemical nature, Cocaine is a tropane alkaloid whereas Hygrine and Cuscohygrine are alkaloids of pyrrolidone moiety. All of them exert euphoric effect. Studies indicate that Bolivian and Peruvian Coca leaves contain highest level of Cocaine as also the total alkaloids content. In addition to alkaloids, the leaf possesses significant level of flavonoids, tannins, essential oil, terpenes, vitamins A, B and C and numerous minerals particularly Calcium and Iron. About 100 g of leaves can provide adequate amount or the daily recommended dose of vitamins and minerals. For this reason, it is claimed to be a super food and by all means it is included in the regular diet of the Andean indigenous population. Interestingly, both fresh and dried leaves hold almost identical food values. The adequate consumption per day balances appropriate sugar level in circulating plasma also maintaining the normal blood pressure. It uniquely regulates the blood oxygen level improving its absorption in the body due to thin air at high altitude of the mountain.
The biosynthesis of tropane alkaloids is extensively studied in different plant systems including Erythroxylum coca, the actual coca plant. It has been identified that the tropane ring has been bio-synthesized from the amino acid, ornithine. Similar situation arises in the case of pyrrolidone alkaloid, Hygrine and Cuscohygrine as well as the Nicotine which is derived from ornithine and nicotinic acid. Below is the biosynthetic pathway for several alkaloids of Coca plant.
The compound Hygrine – α – carboxylic acid is further metabolized to produce cocaine, Ecgonine, methyl Ecgonine, benzyl-Ecgonine, isomers of Truxilline and others. Cocaine has four stereo-specific centers producing sixteen isomers but which one exerts the physiologic effect is exactly unknown. It is a logical assumption that all of them produces the concerted effects.
The leaves act as a good aphrodisiac also significantly suppress the appetite. It is a potent animating compound exerting considerable physiologic stimulation. Due to its euphoric ability, Cocaine earns a bad rap but chewing leaves would not contribute enough level to induce any euphoria. On the other hand, if mixed with Trichocereus cacti, it acts as powerful stimulant that creates strong psychedelic effect. Trichocereus cacti has loads of alkaloids with Phenyl-ethylamine moiety. They are enable to induce hallucinogenic effect like, Mescaline, Anaholidine, Anahaline, Hordenine, Tyramine, 3 – methoxy tyramine etc. Mescaline is a potent psychedelic compound comparable to LSD or Psilocybin (found in several mushrooms). Cocaine released during chewing converts to pharmacologically inactive metabolite Ecgonine, a tropane alkaloid which stays within the body for about seven hours at a very low concentration. Whereas Cocaine itself would retain in the circulation for not more than two hours. Chewing Coca leaf on daily basis do not establish the addiction. The fact has been verified by number of studies. When chewed, it takes few minutes for cocaine and other ingredients to be spread inside the mouth. At that time, the numbness is felt in mucous membrane. The stimulus effect appears within 5 – 10 minutes which later increases with time and thereafter becomes leveled off and afterward quickly goes down within ~ 45 minutes.
The extracted illicit cocaine use produces euphoria with simultaneous excitation of CNS neurons and local numbness due to its anesthetic role. Afterward it brings depression. The continuous use has a habit-forming effect that eventually leads to the serious drug abuse behavior. It also induces hallucinations and psychotic effect. If contaminated with others like in the case of street cocaine, it creates danger to the mind, spirit and health of the users. Often the overdose produces coma. One should keep in mind that although the Coca leaves produces low level of cocaine but it is not for the sake recreational abuse. It is a folk medicine to the Andean indigenous people thus should be treated with proper respect.
Coca leaf by itself does not induce any dependence or abstinence even after the prolong use. Due to this non-addictive property, use of Coca leaf is a suggested method for helping the recovering cocaine addicts. In recent days the herbicide, Glyphosphate (synthesized by Monsanto) resistant Coca plant, Boliviana negra has been created by the Bolivian farmers to protect their cash crop by following natural process of selective breeding. It is for their survival to fight against the Coca eradication campaign by aerial spraying of Glyphosphate conducted by the US and Colombian army for repressing the indigenous population.
Effect of Cocaine on brain / CNS: Action of Cocaine is primarily relayed via the action of Dopamine in brain. During regular neural communication, the released Dopamine from a neuron within synaptic space binds with its targeted receptors situated on a neighboring neuron. In this way, Dopamine acts as a chemical messenger propagating signal within the neuronal network. Whereas the other protein, Dopamine transporter removes away excess / unused Dopamine from that synaptic space by recycling back to the former neuron for further use. The use of Cocaine intervene this normal communication process by binding with the Dopamine transporter protein thereby preventing Dopamine’s reuptake from the synaptic gap. So, the excessive accumulation of Dopamine within synaptic space heavily amplifies the signal of the receiving neurons. As a result, the event creates euphoria and stimulation usually felt right after taking the Cocaine. The entire effect lasts for not more than an hour (t1/2 ~ 10 mins). Besides inducing the euphoria, small doses often make energetic, mentally alert as well as talkative. Additionally, they turn hypersensitive to light, sound and touch. Temporarily it also deprives sleep and lowers the food intake. It helps perform physical and mental tasks with ease although some feel the opposite.
On the other hand, the repeated use of Cocaine brings long lasting changes in the brain. The change is observed within Nucleus Accumbens (NA). Its continuous use leads to neuroadaptations while releasing significant amount of excitatory neurotransmitter, Glutamate that eventually disrupts the overall Glutamate transmission system including the level of its receptor, which is the reward pathway located within NA. The glutamate system is responsible for reward pathway. Often anti-addiction medicines target it to block that pathway, the event of neuroadaptation. Further, its continuous use also develops stress. Since brain starts to adapt so the reward pathway turns less sensitive whereas neural circuits involved in stress become over sensitive expressing intense level of displeasure often bringing violence or negative moods if not taking any Cocaine. This is a classic withdrawal symptom. Under this situation the abuser desperately looks after cocaine showing complete disregard toward any relationship, food or social norms and rewards. On the other hand, the release of stress hormone by cocaine also helps acquiring the neuroadaptation. Stress usually contributes to the relapse, simultaneously disorders created by cocaine also create stress-related disorders. Further due to frequent use, tolerance is developed so higher doses are more and more needed to experience similar level of drug induced pleasure. Eventually, the tolerance leads to the toxicity imposing over dosing which often brings fatality. The stress circuits are distinctly different from reward pathway but they too often overlap. The Ventral tegmental area (VTA) acts as the integration site relaying information about both stress and signal for Cocaine to other brain sites even the one searching for it. It has been experimentally verified that repeated users always look for it in case of stress. The more they use that produces more stress eventually affecting the behavior.
Other physiologic effects of Cocaine: The major effects that are produced due to the intake of Cocaine are, constriction of blood vessels, pupil dilation, rise of body temperature, increase of heart rate and blood pressure. Administering the high dose at a time often leads to erratic and violent behavior. The users might also feel abdominal pain, restlessness, anxiety, vertigo, tremor, panic, paranoia and muscle twitching. The additional reported medical complications are arrhythmia, heart attacks, strokes, severe headaches and coma. The combination of alcohol and Cocaine makes the situation deadly because of the formation of Cocaethylene inside the body which is ethyl ester of Cocaine. The compound potentiates effects imposed by the cocaine.
Pharmacological effects of Cocaine related components in Coca leaf: These compounds behave like Cocaine to a certain extent but devoid of few other effects.
Benzoyl-Ecgonine – It is a major metabolite of Cocaine. But unlike Cocaine, it does not show anesthetic property but exerts potent stimulus action. It blocks the Dopamine reuptake by its transporter thus behave in many aspects like Cocaine.
Methyl-Ecgonine – It also shows no anesthetic effect but prevents Dopamine reuptake by binding to the transporter.
Pseudotropine – It does not show any behavior of atropine.
Benzoyltropine – It has strong cholinolytic action but showing no anesthetic effect. It is an antagonist of Serotonin also inhibits Dopamine and Nor-epinephrine uptake in cortex and striatum.
Tropacocaine – It has same anesthetic effect like Cocaine but possesses much less toxicity. It also prevents Dopamine and Nor-epinephrine uptake in cortex and striatum.
Cuscohygrine – It inhibits delayed type hypersensitivity.
Hygrine – It shows no anesthetic role unlike Cocaine but possesses some of its role.
Conclusion: The restriction imposed behind the use of Coca leaves is not just for the Cocaine which is nothing but an eye wash. It is mainly for the sake of protecting the monopoly business right of Coca-Cola. The plant possesses enormous medicinal virtues which is extremely beneficial for the human health.