Erythroxylum spp. (‘coca’): a versatile and controversial medicinal plant

Erythroxylum spp, better known as ‘coca’, have been an essential part of different cultures in Latin America over thousands of years. Coca leaf is used in social interactions, as medicine, food and in magical-religious rituals. Due to one of its ingredients, cocaine, the plant was banned and added to the Single Convention on Narcotics in 1961. The controversy that has arisen around the coca leaf, cocaine and its derivatives has had a major impact on research into its medicinal properties. This article discusses some of the effects of coca that are well known in Europe, namely its effects on hunger, staying at high altitude, in cold circumstances and for endurance.

Maaike van Kregten
Nederlands Tijdschrift voor Fytotherapie 2016 nr. 3

The coca plant belongs to the genus Erythroxylum P. Browne of the tropical plant family Erythroxylaceae. Ethnobotanist Timothy Plowman (1944-1989) investigated this family extensively. He indicates that the genus consists of around 230 species, most of which are in the tropical regions of the American continents with 187 native to the tropics. Varieties are also found in Africa, Madagascar, India, Tropical Asia and Oceania.

Plowman distinguished two cultivated species known as coca, namely Erythroxylum coca Lam. and E. novogranatense (D. Morris) Hieron, with four subspecies: E. coca var. coca, E. coca var. Ipadu Plowman, E. novogranatense var. novogranatense and E. novogranatense var. truxillense (Rusby) Plowman.*

Although these species differ from each other in composition, all of these cultivated species contain cocaine. Not every wild species contains this alkaloid, but outside Latin America other wild species are also used in traditional medicine [1].

The plant was probably cultivated about 4,000 years ago from Nicaragua to Chile. It was grown in the mountains on terraces (E. coca) or on flat ground (E. novogranatense) in Venezuela, Colombia, Ecuador, Peru, Bolivia and perhaps the north of Chile [2]. Coca is considered the oldest cultivated plant on the South American continent [3].

Archaeological finds from, for example, ceramics, mummies and coca-paraphernalia show that coca had a place in various pre-Columbian cultures. The oldest findings to this date are from around 2500 – 1800 BC and were discovered in Huaca Prieta on the north coast of Peru [1,2,3,4].  These findings also indicate that the way coca is used has remained virtually the same.

Coca is still a popular medicine in South America and it is available in various forms. There are about seventy different folk remedies based on coca with about 80% of the rural population of the Andes using coca for a variety of ailments. It is most commonly used by ‘chewing’ and as mate de coca (coca tea), but is also used to make cataplasms where the leaf is placed on the part of the body experiencing pain. The leaf may or may not be pre-chewed [5].

The most well-known applications in Europe are for pain, fatigue, hunger and cold, but it is also used for stomach pain, intestinal cramps, nausea, indigestion, constipation and diarrhoea. It is supposed to regulate the digestive system. It is chewed or kept in the mouth to mitigate toothache and painful mouth ulcers. It is also used for fractures and for disinfecting and healing wounds [2,6].

Pharmacology and toxicology
There is a significant empirical knowledge about the effects of coca. However, much of the research has been done on the cocaine content in the leaf and most of the research on medical applications has also been done with the isolated tropane alkaloid. This creates a distorted image of the effect of the coca leaf. The effects of coca are probably an interplay of multiple ingredients, many of which are not yet clear [6].

Both the cocaine content and the other ingredients are different per species and per season. For example, E. novogranatense differs fundamentally from E. coca in both alkaloids and flavonoids. In addition, it contains methyl salicylate, which does not occur in E. coca. E. novogranatense var. truxillense contains the highest methyl salicylate content. E. coca var. coca and E. coca var. ipadu have the same flavonoids profile. E. novogranatense var. truxillense has in common with both varieties of E. coca the 3-0-arabinosides of kaempferol and quercetin, which do not occur in E. novogranatense var. novogranatense. Both varieties of E. novogranatense contain the special flavonoid 4′, 7-di-O-methyl quercetin-3-O-rutinoside, which is not found in E. coca [1,7].

A coca leaf contains on average between 0.1 and 0.9% cocaine. According to a Bolivian study, after chewing 30 g of coca leaf, the cocaine content in the blood was around 98 ng [6]. However, the mouth can only contain around 8-10 g of leaves at any one time. It remains in the cheek cavity for a while, making the extraction slow and, moreover, not all cocaine is extracted during this process. The leaves are spit out after a period [3]. In addition, the half-life of cocaine varies from half an hour to an hour and a half. In reality, the average dose of ingested cocaine by chewing will therefore be lower, since most people do not use that much coca and the user does not absorb everything. A line of cocaine, on the other hand, contains approximately 20–50 mg of the cocaine hydrochloride, and a frequent cocaine user takes more than one line. The concentration of cocaine in the blood when using purified cocaine is almost fifty times higher than when chewing the leaf [6].

The toxic effects of the other alkaloids in coca leaves seem to be considerably less than the effect of cocaine. A toxicological study in rats showed that benzoylecgonin and ecgonin methyl ester (ecgonin is a tropane alkaloid from coca, ed.) did not show as much toxic effects as cocaine when administered in the same amount. At a dosage that was 30 to 60 times higher, slight behavioral changes were noticeable. The study also found that benzoylecgonine, at doses 100 times higher than that of cocaine, was still not fatal [6].

Traditional coca users therefore consume very little cocaine, in contrast to users of the pure isolate. Moreover, in countries where coca is used, consumption is regulated by culture and tradition. For example, there are social rules for use and this remains the same for the individual user in terms of quantity and frequency [3].

Biondich and Joslin (2016) indicate that there is no evidence in the literature that the use of coca leads to addiction or withdrawal symptoms [6]. Conscripts in Peru, who had the habit of chewing coca, did not show withdrawal symptoms when they had to refrain from it. Urbanization can lead to reduced access to coca, but no withdrawal symptoms have been observed in migrants either [3,5].

According to traditional users, coca suppresses the feeling of hunger. Research shows that it has an effect on glucose homoeostasis. A low blood glucose level causes, among other things, a feeling of ‘hunger’. Chewing coca raises blood glucose levels, which may explain why users claim that coca reduces hunger[6].

A known objection to this effect is that it could lead to malnutrition. The idea that coca satisfies hunger, which in turn leads to reduced food intake and thus to malnutrition, has proved to be a persistent myth. In the years 1930-1950, Carlos Gutiérrez Noriega, an advocate of the ban on the use of the leaves, drew up a hypothesis that was used in the final prohibition of the plant. His claim was that the use of coca leads to malnutrition. He based his idea on the unilateral diet of the users, omitting factors such as poverty and food availability. If there is a connection, it would be more plausible the other way around: poverty leads to reduced food intake, hunger and malnutrition, which leads to coca being used to suppress hunger [8]. Although coca can suppress the feeling of hunger, it does not stop users from eating when possible [3,9].

In contrast to the Gutiérrez’ hypothesis, coca may well exceed a daily recommended amount of various vitamins and minerals. In 1975, Duke, Aulik and Plowman conducted research into the nutritional value of Erythroxylum coca Lam. and compared it to 50 other Latin American vegetables. They concluded that 100 gr. coca has a higher calorie content (305 vs. 279). In addition, coca contains more proteins (18.9 g vs. 11.4 g), carbohydrates (46.2 g vs. 37.1 g), fiber (14.4 g vs. 3.2 g), calcium (1,540 mg vs. 99 mg), phosphorus (911 mg vs. 270 mg), iron (45.8 mg vs. 3.6 mg), vitamin A (11,000 IU vs. 135 IU) and riboflavin (1.91 mg vs. 0, 18 mg) [10].

Altitude sickness
Preventing altitude sickness is perhaps the most well-known medicinal use of coca by travelers. The thin air at high altitude causes, among other things, headache and dizziness. Upon arrival in the Andes, the tourist is very frequently offered coca tea. Coca users indicate that they suffer less from the cold and from headache, dizziness and fatigue caused by hypoxia (lack of oxygen).

 A link between altitude and the use of coca is often assumed, because the higher the altitude, the more and more often people chew coca[3,6,9], but altitude is not the only explanation for the use of the leaf. When historical, archaeological, botanical and anthropological data are included, a more complete picture emerges. Bray and Dollery (1983) demonstrate that in the period before the arrival of the Europeans, coca was used in both high and low land and that the use extended from Nicaragua to Chile. The regions where coca is currently consumed the most, are those where the traditional Indian culture is best preserved. This applies to both high and low land [11]. Therefore, relative altitude is just one of the reasons why people use coca.

A physiological response to life in, or prolonged stays at, high altitudes is the production of more red blood cells, so the body can still be supplied with sufficient oxygen. If too many erythrocytes have been created, this is referred to as (secondary) polycythemia. Symptoms of this disease partly correspond to those of altitude sickness, namely fatigue and headache. Chewing coca relieves these symptoms.

A hypothesis that is often cited is that of Fuchs (1978): he assumes that hypoxia inevitably leads to polycythemia and that this is common among residents of the Andes. He claims that coca reduces the number of erythrocytes. Oxygen deficiency increases the number of red blood cells, coca brings it down again, according to Fuchs. He further substantiates this by indicating that miners, who have an oxygen deficiency due to silicosis (black lung), use most coca. They do not always work at high altitudes. According to Fuchs, they use coca to relieve the polycythemia they have contracted due to silicosis. He suggests that cocaine and the metabolite ecgonin, perhaps inhibit erythropoiesis, thereby alleviating the symptoms of polycythemia [12].

However, there are objections to this hypothesis. First, the research on which the hypothesis is based: the village where most people used coca is located at only 720m. Hypoxia usually starts on average at an altitude of 3000m, which means that there are no circumstances in which to develop polycythemia [13]. Secondly, the hematocrit level (amount of red blood cells per litre of blood) of the majority of both coca users and the control group was far below the value at which polycythemia is diagnosed [14]. Thirdly, polycythemia in the Andes does not seem to be as common as is often assumed. Polycythemia has clinical effects on cardiovascular functions when the hematocrit value is above 70% of the normal value [19]. Garruto and Dutt (1983) examined 303 men, ages 6-57 who live at 4,200 meters. They found a difference of only 10–12% more erythrocytes in all age groups compared to people living at sea level.

Garruto and Dutt showed that the hypothesis that Andean residents suffer from polycythemia, is untenable as most of the studies have been done with miners and not with ‘normal’ people of all ages. Miners have a different pathology than healthy inhabitants of the high mountains. For example, a study of miners demonstrated a strong link between silicosis and polycythemia. Garruto and Dutt assume that when polycythemia occurs, this can be a combination of several factors, such as chronic respiratory problems and altitude. The reaction in that case is also pathological and not only adaptive [15].

The Bolivian Institute of Altitude Biology (IBBA) notes that people  commence coca between the ages of twenty to thirty years. In the Garruto and Dutt study, most of the adults used coca. Children and adolescents in the mountains who do not use coca should have a clearly higher hematocrit level compared to the same age group at sea level. If coca were to inhibit erythropoiesis, this difference should be lower in adults who use coca. Nevertheless, the same percentage difference was found in the latter group as in children and adolescents.

The author of this article visited high altitudes in Bolivia in 1996 and understood that the local population suspected that coca actually stimulates the production of red blood cells, so that the body adapts more quickly to altitude. When one spends some time in high altitude areas, an increase in red blood cells is a functional response of the body; it adapts to the circumstances. If coca were to inhibit erythropoiesis, it would probably not be used to prevent altitude sickness. Rodríguez et al. (1997) found a stronger increase in hemoglobin and hematocrit value when coca was used compared to the control group [16]. Coca may have a regulatory effect if it can both inhibit and stimulate the production of red blood cells.

Users indicate that they benefit from coca as it enables them to be more resistant to the cold climate that occurs at high altitudes, making them feel warmer. Hanna (1971) investigated this by having fourteen men chew coca while being exposed to a temperature of 15.5 °C for two hours. The researcher compared this to the same group as controls under the same circumstances, with the exception of coca. The subjects showed lower temperatures of hands and feet when they used coca. Moreover, they showed a more gradual decrease in body temperature during the second hour. In addition, the coca group exhibited higher temperatures of the head. The effect was attributed to a mild peripheral vasoconstriction induced by coca-chewing, so that body heat could be better preserved [17].

An earlier study by Little (1970), however, showed no difference in temperature of the feet when using coca [18]. Neither Hanna nor Little state what type of coca is used. However, Hanna has used a much higher dosage than Little. Hanna gave the test subjects 50 g of leaf, with the instruction to chew all day prior to the experiment. During the Hanna experiment, the subjects chewed at least 45 g per hour during the two-hour exposure to 15.5 °C. Little gave 3-4 g coca during the experiment, which lasted an hour at 0 °C. The different outcomes may have to do with the design of the studies, in particular the dosage and frequency of use. Because botanical names are missing, the coca species may also have had an effect on the effects.

In addition, coca is used in both high and lowlands. The lowlands have a tropical climate and the need for more body heat is unlikely. Miners, the largest group of coca users, are in circumstances where it can be hot or cold. Mines are located at heights as well as in the lowlands, but also at heights it can be warm inside a mine. So it doesn’t seems plausible that coca is traditionally used for raising body temperature, unless there are other factors involved, such as dosage or species.

Traditional users indicate that they have more endurance and are less tired when they consume coca. This effect has become known in Europe by the Corsican pharmacist Angelo Mariani, who at the end of the nineteenth century introduced a wine based on coca leaf extract, which he recommended as a strengthening agent. Mariani made various coca products, including Vélo Coca: doping for cyclists [19].

Several researchers have investigated the stimulating effect of coca (Favier et al. 1996; idem 1997 and Spielvogel et al. 1996). All saw only an increased stability of glucose homoeostasis [6]. Casikar et al. (2010) can draw clearer conclusions. The results of their pilot study suggest that by chewing glycolysis (degradation of glucose) is blocked by inhibiting pyruvate kinase, resulting in accumulation of glucose and pyruvate. The energy requirement during exercise in that case is met by degradation of fats through beta-oxidation of fatty acids. The researchers indicate that it seems that chewing coca leaves has a reinforcing effect on the energy supply in the event of prolonged (uniform) moderate exercise. In addition, it appears that the energy supply from the fat reserves in the body seems to be stimulated, which is required for prolonged exercise. These experimental findings indicate that chewing coca can be useful during physical exertion and that its effects can be felt over a longer period of time.

Casikar et al. also suggest that it is possible that the positive effects of coca leaves are related to the flavonoids in the leaf and not to cocaine. They state that the amount of cocaine released by traditional use is extremely small and is not likely to have any physiological benefit [20]. An objection to this small study, however, is that only four out of ten subjects wanted to donate blood twice. It is also not known with which type of coca the research was done.

The aforementioned study by Rodríguez et al. (1997) showed that coca can provide the body with more oxygen by producing more erythrocytes, which could also improve endurance. In combination with the results of Casikar et al: has the tip of the veil been lifted?

Research into the mechanisms of action of Erythroxylum spp. is an almost unexplored area. In many of the studies, the focus is only on one substance, the importance of which is under discussion. In addition, in most studies about leaf efficacy, it is not specified what type of Erythroxylum has been used. Therefore very little is known about the mechanisms of action of ‘coca’ and even less about the differences in effects between the various species and varieties.

However, empirical information is abundant and can be a source of inspiration for further research, for example into the alleged regulatory effect on digestion and possibly also on erythropoiesis. A multidisciplinary approach to research is desirable, because a plant with as many facets as coca cannot be easily explained

* The current taxonomic classification according to and/or IPNI is as follows: Erythroxylum coca Lam. is an accepted name. Erythroxylum coca var. coca is a synonym. Erythroxylum coca var. ipadu Plowman is an accepted name (IPNI). Erythroxylum novogranatense (D.Morris) Hieron. is an accepted name. Synoyms are: Erythroxylum novogranatense var. novogranatense, Erythroxylum coca var. novogranatense and Erythroxylum coca var. novogranatense D.Morris. Erythroxylum novogranatense var. truxillense (Rusby) Plowman is an accepted name.

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