Erythroxylum (PROSEA Medicinal plants)
Erythroxylum P. Browne
- Protologue: Civ. nat. hist. Jamaica: 278 (1756).
- Family: Erythroxylaceae
- Chromosome number: x= 12; E. coca: 2n= 24, E. novogranatense: 2n= 24
Erythroxylum coca Lamk, E. novogranatense (Morris) Hieron.
- Coca (En, Fr).
Origin and geographic distribution
Erythroxylum , which has about 250 species, is pantropical and its centre of diversity is in the Andes and the Amazon basin in South America. There are 6 indigenous species and 2 cultivated species in the Malesian region. The two species that are medicinally most important, E. coca and E. novogranatense , contain cocaine. They are native to South America, and were introduced into South-East Asia by the end of the 19th Century.
The dried leaves of Erythroxylum spp. have been used in South America for at least 5000 years as a masticatory to allay hunger and fatigue, and as an element in religious rituals. Many medicinal applications have been recorded for coca in South America: infusions of coca leaves are used to treat indigestion and other stomach complaints, and altitude sickness. Coca is also reported to be effective against respiratory problems, teeth and gum complaints, malaria, eye irritations and sore throat, and it is valued as an aphrodisiac and a means of ensuring longevity. In some countries, e.g. Bolivia, the leaves are also used in infusions ("maté de coca") which are consumed like coffee or tea.
E. coca and E. novogranatense are a source of cocaine, which is used medicinally or as a narcotic. The therapeutic importance of cocaine has declined considerably. Cocaine (in its form as a hydrochloride) has long been used as a local anaesthetic in ear, nose and throat surgery. Although it is applied locally, systemic absorption may be marked, giving side effects (e.g. tachycardia, euphoria). It has been replaced by less toxic agents at present. Cocaine (hydrochloride) also used to be the sole active component in analgesic potions, or was added to oral solutions containing salts of morphine in order to potentiate the analgesic effect. These applications, however, are considered obsolete today. As a narcotic, cocaine is consumed in various ways. Coca paste, the initial product of extraction of the leaves, contains 40-70% cocaine (base), and is smoked. Cocaine (hydrochloride) is usually inhaled through the nose. "Crack" or "rock", a pure form of cocaine base, obtained by treating cocaine hydrochloride with bicarbonate, is smoked too ("freebasing").
The cola soft drink originally included coca extracts and caffeine-rich extracts from Cola nitida (Vent.) Schott & Endl., but nowadays coca leaves are only used to flavour the syrup after the cocaine has been removed from them.
The leaves of E. cuneatum (Miq.) Kurz are reported to be used as fish poison in the Philippines (Luzon). E. cuneatum is also planted as an ornamental. The leaves of E. ecarinatum Burck are used medicinally, known as "obat jaguar" in Sulawesi. In Papua New Guinea (Morobe Highlands), leaves are chewed and the sap ingested with traditional wood-ash salt against an upset stomach.
The wood of Erythroxylum has been used for fence posts and poles, flooring and sometimes for local house building, bridges, boat building and tool handles.
Production and international trade
Coca is cultivated extensively in South America (Peru, Argentina, Bolivia, Colombia and Brazil), but also in Java, Sri Lanka, Taiwan, India and the United States. Few statistics are available on coca production. In South America, most of the coca leaves produced are consumed locally; very little is exported. Part of the coca leaves are used to make cocaine for illegal trafficking. Illegal imports of cocaine into the United States and Europe in 1988 were estimated at 100 t and 50-60 t, respectively.
The most important constituent of E. coca and E. novogranatense is the tropane-ester alkaloid cocaine (methylbenzoyl ecgonine). The tropane part of the molecule, ecgonine, is biosynthetically derived from the amino acid ornithine. In the plant, cocaine occurs alongside other derivatives of tropine, e.g. cis- and trans-cinnamyl cocaine and tropa cocaine, and pyrrolidines e.g. hygrine, hygroline and cuscohygrine.
Cocaine and cinnamyl cocaine are considered to be the naturally occurring alkaloids of the coca plant, and have been identified in the roots, bark and leaves of several species and varieties. The younger leaves seem to accumulate cinnamyl cocaine as the main alkaloid, but the older leaves contain mainly cocaine. In an extensive study, the cocaine content in leaves of E. coca var. coca (30 samples) was found to range from 0.23-0.96%, with a mean of 0.63%, while the cocaine content in E. coca var. ipadu (6 samples) was lower: 0.11-0.41%, with an average of 0.25%. E. novogranatense var. novogranatense (3 samples) contained 0.55-0.93% cocaine, with an average of 0.77% and E. novogranatense var. truxillense (14 samples) 0.42-1.02%, with a mean of 0.72%. Cocaine (0.0003-0.3%) was detected in the leaves of 13 out of 29 wild Erythroxylum species, but no cocaine was detected in Old World species. The drug "Cocae Folium" is also known to contain α-and γ-truxilline and benzoyl ecgonine. These components are probably formed during harvesting and processing of coca leaves: truxillines are dimers of cinnamoyl cocaine, and hydrolysis of cocaine leads amongst others to benzoyl ecgonine.
Cocaine was first isolated around 1859. The compound displays several pharmacological activities, the best known being its local anaesthetic action. In this respect, cocaine acts by blocking Na+ion channels in the neuron membranes, slowing down impulse conduction, and finally interrupting the propagation of action potentials. Because of cocaine's toxicity and addictive properties, a search for synthetic substitutes began. This is why the general molecular structure of cocaine can be found in several well-known local anaesthetics, e.g. procaine and tetracaine. Besides being a local anaesthetic, cocaine also acts as an adrenergic stimulant, by blocking the re-uptake of catecholamines (noradrenaline (= norepinefrine), dopamine) in both the peripheral and central nervous systems. Its euphoric properties are primarily due to inhibition of catecholamine uptake, particularly that of dopamine, at central nervous system synapses.
The chewing of coca leaves is a well-known practice in several South American countries. Alkalis added to the coca leaves facilitate the release of cocaine in its basic form. As a base, the ester is also volatile and can be smoked. Occasional use of cocaine results in feelings of mood elevation, vitality, mental clarity, sexual stimulation and reduction in appetite. However, chronic use can lead to anxiety, confusion, insomnia and impotence, and long-term heavy use can lead to paranoid psychosis. There are also indications that cocaine can be detrimental to fetal development. Regular use of cocaine finally leads to psychic dependence, but in contrast to heroin, not to physical dependence.
Adulterations and substitutes
Although cocaine itself has never been synthesized, this has been done with similar compounds, of which procaine is the most important. Synthetic alkaloids with a similar action have almost completely replaced cocaine in medical use in the United States.
Shrubs or small trees. Leaves simple, alternate, distichous, entire; stipules intrapetiolar, inserted semi-amplexicaulously, mostly entirely connate, rarely bifid, sometimes emarginate or 2-toothed at the apex, often bicarinate, long-persistent or early caducous, leaving a distinct scar, involute in bud, the margins leaving a subpermanent trace as 2 longitudinal lines on the upper leaf surface ("areolate"). Flowers in axils of leaves, solitary or in clusters, bisexual, 5-merous, actinomorphic, often heterodistylous, or even heterotristylous; pedicel slightly thickened, often only under the calyx, with 2 bracteoles at the base; calyx campanulate, persistent; petals free, alternating with the calyx lobes, caducous, quincuncial in bud, nearly always provided with an emarginate or 3-lobed ligule inserted on the apex of the claw; stamens in 2 whorls of 5, persistent, filaments towards the base connate into a staminal tube, anthers ellipsoid, basifixed, cordate at the base, 2-celled; ovary superior, (1-)3-celled, normally only 1 cell fertile, each cell with 1 ovule, ovules pendulous, anatropous, with a ventral raphe, styles 3, erect, free or partly connate or stigmas sessile. Fruit a drupe. Seed with or without endosperm, embryo oblong, erect, cotyledons flat to plano-convex, plumule absent, radicle distinct.
Growth and development
E. novogranatense seed starts to germinate in 2-3 weeks after planting. Three months after germination the plants may have attained a height of 15 cm. The first harvest, usually 1-3 years after transplanting into the field, consists of the main shoot that is pruned to promote frame formation as in tea ( Camellia sinensis (L.) Kuntze). Consecutive pruning is carried out when coca develops flower buds; this coincides with a maximum in harvestable leaves. Leaf harvesting brings E. coca plants from the vegetative into the reproductive development phase.
Other botanical information
Cocaine-rich leaves are obtained from 4 taxa: E. coca var. coca (Bolivian or Huánoco coca), E. coca var. ipadu Plowman (Amazonian coca), E. novogranatense var. novogranatense (Colombian coca) and E. novogranatense var. truxillense (Rusby) Plowman (Trujillo coca). E. coca var. coca is considered the ancestor, while E. novogranatense var. truxillense is derived from it, and E. novogranatense var. novogranatense derived from E. novogranatense var. truxillense . Cultivation and selection has probably been the main selective force. E. coca var. ipadu is considered to be a cultivar selected by man from E. coca var. coca . Wild populations of E. coca var. coca are found in the eastern Andes, but the other 3 taxa are only known as cultivated plants. Crosses between E. coca var. coca and E. novogranatense var. novogranatense have failed. Crosses between E. coca and E. novogranatense var. truxillense have been made, but gave abnormal, dwarfed progenies.
In the past Erythroxylum has been incorporated in different families, i.e. Malpighiaceae , Linaceae and Erythroxylaceae . In recent systems of classification it is widely accepted that the Erythroxylaceae differ from the Malpighiaceae by their unwinged fruits that do not split into 3 nut-like parts at maturity, and from the Linaceae by their ligulate petals and 3-locular ovary with only one fully developed locule.
E. coca var. coca is well adapted to the eastern Andes of Peru and Bolivia, an area of humid, tropical montane forest, whereas E. coca var. ipadu is cultivated in the lowland Amazonian basin. E. novogranatense is cultivated in drier regions in South America. However, E. novogranatense var. novogranatense is very adaptable to varying ecological conditions, and grows well in both humid and dry areas, and at low and higher altitudes. In Java, E. novogranatense has been cultivated from sea-level to 1000 m altitude, with best results at 400-600 m. In controlled environment studies, the optimum average daily temperature for leaf growth for both E. coca and E. novogranatense var. novogranatense was found to be around 27°C, whereas leaf growth was generally higher at photosynthetic photon flux densities of 250 or 400 μmol.m-2.s-1than at 155 μmol.m-2.s-1. Environmental effects on the cocaine concentration in the leaves were smaller, so that total cocaine production per plant was largely a function of leaf mass, with environmental conditions that stimulated leaf growth giving higher cocaine yields. Both species grow on soils with low pH, and a greenhouse study has shown that the optimum pH for biomass accumulation of E. coca and E. novogranatense is as low as 3.5 and 4.7-6.0, respectively.
Propagation and planting
E. novogranatense var. novogranatense , E. novogranatense var. truxillense and E. coca var. coca have to be reproduced by seed, because vegetative propagation is difficult. However, E. coca var. ipadu does not produce seed and is propagated by stem cuttings. It cannot reproduce without human interference. Cultivated E. novogranatense var. novogranatense produces abundant seed and is easy to propagate. Seed viability decreases rapidly. Germination percentages of E. coca and E. novogranatense seed were found to decrease from around 95% and 89% directly after harvesting to 29% and 0%, respectively, after 24 days' storage at 4°C. Coca seedlings are usually sown in shaded nurseries and transplanted to the field when they are about one year old and 20-25 cm tall. In the field, they are planted at a spacing of 1-2 m. The actual time of transplanting and the spacing of the plants varies with climatic factors and whether coca is interplanted or cultivated as a sole crop.
In vitro production of active compounds
It is possible to obtain cocaine and other alkaloids from E. coca var. coca shoot tissue cultures. The levels of cocaine produced have been found to be 50% of that produced by the parent plant, but within the range of the species. Whereas in Solanaceae the tropane alkaloids are biosynthesized in the roots, in E. coca tropane alkaloids (e.g. cocaine) can be produced from rootless explants.
In mountain areas, coca is often grown on terraced fields. The fields are often manured with ash or plant material to sustain production. Older plants are severely pruned when leaf production decreases, after which regrowth occurs, but coca plantings are usually renewed after 20 years. E. coca var. ipadu is grown by semi-nomadic Amazonian tribes in isolated small plots, and constitutes an important part of their shifting cultivation system.
Diseases and pests
Erythroxylum spp. are susceptible to Fusarium wilt, caused by the host-specific fungus Fusarium oxysporum , which is considered a potential mycoherbicide to combat illegal coca production. Symptoms are vascular wilt and permanent defoliation.
The first harvest of coca takes place at 1-3 years after transplanting. In Java, a first harvest can be expected within a year after transplanting. The leaves have to be stiff and easily detachable to be harvested. Leaves can be harvested every 50-60 days in the rainy season, but when it is drier, they are usually harvested every 3-4 months. The leaves should be pinched from the plant, not ripped off.
Annual yields of 1.7-2.2 t dry coca leaves per ha have been reported. The highest yields are obtained between 3 and 10-15 years after transplanting. In the Asian coca plantations, yields are about 700 kg dry coca leaves per ha, with the leaves containing up to 1.4% cocaine.
Handling after harvest
When the leaves of coca are used for cocaine production, they are dried in the sun or artificially. Temperatures should not exceed 40°C, because the cocaine content of the leaves decreases at higher temperatures. The leaves are considered dry when they can be broken. In Asia, dried leaves are ground, pulverized and packed in plastic bags, while in South America they are pressed into bales of about 50 kg for transport. Leaves intended for chewing in South America must keep their form and colour and are dried more carefully.
Genetic resources and breeding
The gene pool of cultivated E. coca has changed little over 5000 years, and wild or abandoned E. coca shows no morphological and genetic differences from cultivated E. coca . No germplasm collection and breeding programmes are known to exist.
The chewing of coca leaves is very important in Indian culture in parts of South America, and therefore coca will remain important there in the future. Elsewhere, the crop will only be important in regions where illegal production of narcotics is possible, because the world market for cocaine for medical use is limited, as synthetic agents have almost completely replaced the use of cocaine as a local anaesthetic.
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R.C.K. Chung & M. Brink