Papaver (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

Papaver L.

Protologue: Sp. pl. 1: 506 (1753); Gen. pl. ed. 5: 224 (1754).

Family: Papaveraceae

Chromosome number: x= 7, 14; P. rhoeas: 2n= 14; P. somniferum: 2n= 20, 22, 36, 44

• Papaver somniferum L.

• Poppy (En).

Papaver consists of about 100 species, most of which are found in the Mediterranean region. The most important species is P. somniferum (opium poppy), the source of opium. The cultivation of Papaver for medicinal purposes dates to about 2000 BC in Mesopotamia. The cultivation of P. somniferum has been prohibited in many countries due to the misuse of opium and its deleterious effects on human health.

About 2350 years ago, the Greek physician Hippocrates mentioned poppy juice ("opium") as a cathartic, hypnotic, narcotic and styptic. P. somniferum is the only source of opium, which is the dried, alkaloid-containing latex obtained from the immature capsules of the plant. When the surface of these unripe fruits is damaged, e.g. by making incisions with a specially designed knife, latex oozes out in the form of white droplets which quickly turn brown and become semi-solid. Commercial opium is used medicinally, as a starting material for the extraction of several medicinally important alkaloids, or as a narcotic.

The only Papaver species with medicinal use in South-East Asia are P. somniferum and P. rhoeas. The dried fruit without the seed of P. somniferum is the "anh tuc xac" of the traditional Vietnamese Pharmacopoeia, used to treat cough and diarrhoea. Dried fruits have also been used to treat cough in Europe and diarrhoea and cough in China. In northern Thailand, as well as in many other countries worldwide, opium is used to treat pain, diarrhoea, cough and insomnia, or as a narcotic. It is sometimes taken orally, but also often smoked, which is habit-forming and may subvert the personality. The major role of opium in medicinal practice has been for its astringent properties. Standardized opium tincture and camphorated opium are prescribed for severe diarrhoea and dysentery, as well as for pain, cough and nausea. Although still present in official pharmacopoeias of some countries, the use of opium or opium preparations has largely been superseded by its purified, extracted alkaloids, mainly morphine, codeine and noscapine (= narcotine).

The flowers and roots of P. rhoeas are recommended in China for treating jaundice and in Japan and the Philippines an infusion of the flowers may be used as a gargle or ingested as a bechic. The petals have a reputation as having mild sedative, antitussive, anodyne and sudorific properties. Infusions or syrups made from the petals have been used as a red colourant in pharmacy; however, they act as litmus, turning red with acid and blue with base.

P. somniferum is also a source of edible seeds and seed oil. The seeds are used in food, for instance in cakes and on bread. They are also used in bird feed. Poppy seed oil is mainly used as an edible oil, but also for the production of paint and soap. Poppy-seed cake or meal left after extraction of the oil is sweet and nutritious and used alone or mixed with other feeds, suitable as food for cattle and other animals. However, its use as animal feed has sometimes resulted in poisoning due to the presence of alkaloids arising from contamination of the seed with particles of the capsule. Some tribes in South-East Asia eat the young leaves of P. somniferum.

In Java, several Papaver species (e.g. P. nudicaule L., P. rhoeas and P. somniferum) used to be grown as ornamentals. They have bright flowers, ranging from white to almost black, and through various shades of yellow, pink, orange, scarlet and crimson.

P. somniferum is cultivated for the production of opium, straw for extraction of alkaloids, and/or seeds and seed oil. Poppy straw consists of the upper stalks with crushed capsules. The legal production of opium is limited to India, but extensive illegal opium production is found in the "Golden Triangle" (the border region of Thailand, Burma (Myanmar) and Laos), the "Golden Crescent" (Pakistan, Afghanistan, Iran), Lebanon and Mexico. Total legal opium production in 1983 was 1000 t, produced in India on about 32 000 ha. The opium-producing areas in Burma (Myanmar), Thailand and Laos were estimated at respectively 60 000 ha, 3500 ha and 3500 ha. Opium production estimates for 1989 were for Burma (Myanmar) 2000 t, for Afghanistan 800 t, for Laos 400 t, for Pakistan 130 t, and for Thailand 50 t.

Production for straw is mainly found in the more temperate zones, being for Spain 13 700 t, for France 3700 t, for Australia 1180 t and for Turkey 940 t in 1980.

A large number of alkaloids have been isolated from Papaver. At least 25 alkaloids that are biosynthetically derived from the amino acid tyrosine have been isolated from opium. The most important are morphine (5-25%), codeine (0.2-3%), thebaine (0.2-5%), noscapine (2-10%), narceine (0.1-0.7%) and papaverine (0.5-3%). Biosynthetical routes are extremely complex within the family of P. somniferum alkaloids, thus several subgroups of related compounds can be recognized. Of the 6 main alkaloids, morphine, codeine and thebaine belong to the phenanthrene (or morphinane) type, noscapine and narceine belong to the phtalide-isoquinoline type, and papaverine to the benzyl-isoquinoline type. Other alkaloids include aporeine, codamine, cryptopine, gnoscopine, hydrocotarnine, lanthopine, laudanidine, laudanine, laudanosine, meconidine, narcotoline, neopine, oxynarcotine, papaveramine, porphyroxine, protopine, reticuline, rhoeadine and xanthaline. Many of these opium alkaloids are not only present in the fruit but also in other parts of P. somniferum.

In opium, the alkaloids are largely present as salts of organic acids, such as meconic or lactic acid. The drug also contains sugars, salts (e.g. sulphates), free organic acids such as meconic, lactic, fumaric and oxalacetic acid, albuminous substances, colouring matters and water. Most of the world legal opium production is used to obtain morphine, codeine and noscapine, which are medicinally the most important. A large part of the isolated morphine is converted into codeine by chemical semisynthesis, since there is much greater demand for this compound. Morphine can also be converted into heroin by addition of acetyl groups; this substance is very addictive.

Morphine (named after Morpheus, the greek god of dreams) as a pure substance is mostly applied as one of its salts (e.g. HCl or sulphate). It is a very strong analgesic, acting on the central nervous system and widely used to relieve pain. Furthermore, morphine has digestive effects leading to constipation, and it is antidiuretic. At high doses it causes depression of respiration, bradycardia, vasodilatation and hypotension, but the best known side effects are the development of psychic and physical dependence. Morphine acts by interaction with specialized receptors, called opioid receptors, of which several types (e.g. μ, κ, σ, δ) are recognized. There is also evidence of the existence of several subtypes. μ-Receptor activation in the brain is presumed to be responsible for the strong central analgesic effect. κ-receptors in the brain and spinal cord also appear capable of producing analgesia, particularly in the spine. Most of the psychomimetic effects (e.g. hallucinations) are apparently mediated by σ-receptors. The δ-receptor is presumed to be the primary receptor for endogenous opioid pentapeptides known as enkephalins. These enkephalins, together with the other endogenous opioid peptide families endorphines and dynorphines, and the opioid receptors, are believed to be responsible for the modulation of nociception, especially in cases of pain. Endogenous opioid peptides regulate respiration (μ-receptor); respiratory depression is therefore a very significant side effect of morphine, even at therapeutic levels. Some endogenous opioid peptides and receptors also exist in tissues and organs other than the brain: the gastro-intestinal tract is another principal site of action (μ-, κ-receptor; decreasing of motility).

Heroin is the diacetyl ester of morphine. The effects of heroin are similar to those of morphine, but it is more addictive and causes disruptions of blood flow, infections and collapsed blood veins. The manufacture and possession of heroin is illegal in most countries.

Codeine is the most widely used opium alkaloid, which also has some analgesic properties of its own. However, it is known to enhance the effects of other (non-opiate) analgesics, and thus it is often given in combination with e.g. paracetamol (acetaminophen). Codeine acts like morphine, but it is far less narcotic, euphoric or constipating. It has strong antitussive properties, and it is often employed in cough medicines and decongestants.

Thebaine is more a convulsant than a narcotic. It may cause tetanic spasms, which do resemble those caused by strychnine. The compound has been used as a narcotic antagonist in the treatment of heroin addiction, although better alternatives (e.g. naloxone) are available at present. Noscapine (narcotine) is not an analgesic, but a moderately strong antitussive. Like codeine, it is often used in cough medicines, especially for children. Papaverine has very little narcotic or analgesic action, but relaxes the involuntary muscles of the body and increases the blood flow by its effects on heart and blood vessels.

The leaves, stems and roots of P. rhoeas contain coptisine and protopine, whereas the capsules contain rhoeadine, rhoeagenine and rhoearubine. The pharmacology of the main alkaloid, rhoeadine (a tetrahydrobenzazepine) is unknown, but closely related derivatives are dopaminergic antagonists and neuroleptics. The presence of P. rhoeas in hay can be dangerous to animals.

The seeds of Papaver are rich in oil, carbohydrates, proteins and calcium. The oil content of 10 different Papaver species was found to range from 35% to 48%, the protein content from 21% to 28%. The fatty acids in poppy-seed oil are linoleic acid (65%), oleic acid (25%) and saturated acids (6-10%).

An alternative source of codeine is P. bracteatum Lindley, which grows wild in mountainous regions in western Asia. It contains thebaine, but no morphine or codeine. Thebaine can easily be converted into codeine and morphine by chemical methods, but is not readily converted into heroin.

Synthetic derivatives of morphine with fewer side effects have been developed, such as meperidine, methadone and fentanyl. However, the isolation of morphine derivatives from natural sources still seems easier and cheaper than synthetic production.

In Western medicine, preparations from hemp (Cannabis sativa L.) were extensively used between the middle of the 19th Century and the Second World War as a milder and less dangerous analgesic than opium.

• Herbs or sometimes shrubs up to 150 cm tall, smooth or hispid, pale green or glaucous, with bitter, milky latex.
• Leaves arranged spirally or in a radical rosette, often deeply incised.
• Flowers solitary, bisexual, long pedicelled; sepals 2-3, free, deciduous when the flower expands; petals 4-6, corrugate in bud, fugacious; stamens numerous, much shorter than corolla; ovary superior, with 4-18 parietal, much intruded placentas and many ovules, stigma sessile, peltate, rather deeply lobed, lobes as many as placentas, opposite to them, radiating.
• Fruit a capsule, globose, urceolate to broadly ovoid, campanulate or cylindrical-clavate, stalk-like contracted at the base, under the stigmatic shield dehiscing by transverse pores (arising by the recurving of short valves).
• Seeds numerous, globose to slightly reniform, reticulate.
• Seedling with sessile or shortly petioled, linear cotyledons, base cuneate; hypocotyl elongate, epicotyl absent.

Most Papaver species are annuals or biennials, including P. rhoeas and P. somniferum. The seed of P. somniferum germinates in 10-15 days. The minimum temperature for germination is around 3°C. The seedling grows slowly; it takes a month to reach the rosette stage. After that, stem differentiation occurs and growth is more rapid. Reproductive buds appear at about one month from the rosette stage. About a week before flowering, the pedicel bends, but it unbends when the flower opens. Flowering occurs about 90-100 days after sowing; the petals are shed within 3 days. After fertilization, the fruit grows fast, reaching its final size within 2 weeks. In another 10-15 days, the fruits become ready for lancing and latex collection. The seeds reach maturity 2 weeks after that.

Papaver spp. have been grouped in different sections, but no consensus exists. Neither is there agreement on the relationship between P. somniferum and P. setigerum DC., which some taxonomists separate, whereas others lump them into one very variable species. Sometimes 3 subspecies are recognized: P. somniferum subsp. somniferum (opium poppy) cultivated and escaped throughout most of Europe, P. somniferum subsp. songaricum Basil. cultivated in the Balkans and Asia, and P. somniferum subsp. setigerum (DC.) Corb. (setaceous poppy) probably native in the western Mediterranean region and a weed elsewhere.

Papaver is found in the relatively dry temperate and subtropical parts of the Old World and does not tolerate tropical lowland conditions. In the "Golden Triangle", opium poppy only grows well when grown above 850 m altitude, and the best opium is obtained from above 1000 m altitude. P. somniferum is a long-day plant. Both P. somniferum and P. rhoeas are adapted to open or disturbed habitats, and commonly found in association with cereal cropping. Regions where it may rain during the latex stage of the crop are not suitable for latex production, because exuded latex may be washed away. Windy areas should be avoided, to prevent lodging of the heavy-capsuled plants. Opium poppy can be grown on a relatively wide range of soils.

Most Papaver species are propagated by seed. Seed is broadcast (3-4 kg/ha) and plants are thinned later to a distance of 20-25 cm when about 10 cm tall. Seedlings resent transplanting. In Tasmania, poppy is sown in rows with 100-150 plants/m². Some hill tribes in the "Golden Triangle" practise staggered planting, to spread the harvest over a longer period, but others sow their fields in one go.

Seed of P. somniferum is very small, with a 1000-seed weight of less than 0.2 g; the colour varies from yellowish-white to purplish-black.

Tissue culture of both P. somniferum and P. bracteatum is possible and may serve as a future technique in commercial production of codeine.

In northern Thailand, P. somniferum is usually sown in September-October after maize on recently cleared land. In India, P. somniferum is sown in November. P. somniferum has high nutrient requirements. It benefits from phosphate fertilization during early growth, whereas later on nitrogen fertilization, at 100-140 kg/ha, will help to increase opium yield and morphine content. Under Tasmanian conditions, irrigation can have a beneficial effect. The crop especially needs adequate water at the start of flowering. Because of the heavy capsules, lodging can be a serious problem at higher plant densities.

In general, P. somniferum is not regarded as very susceptible to diseases and pests. It is reported to be susceptible to downy mildew (Peronospora arborescens), leaf blight (Helminthosporum spp.), root rot (Rhizoctonia sp.) and thread mould (Dactylium roseum). Insect pests include Agrotis suffusa (opium cut worm), Agrotis epsilon, Aphis fabae, Franklinella sp., Heliothis armigera, Myzus persicae, Nephotettix sp., Pachycephus smyrnensis and Phytomyza horticola.

Latex is collected before the capsules are mature and dry. They are carefully incised; the depth of the incision is very important. It must be deep enough to reach the laticiferous ducts, but not so deep that it cuts into the endocarp, otherwise the latex flows inside the capsule. Lancing or scarification is done in the afternoon. The exuding latex is then left to coagulate overnight, during which time it will become darker and thicker. The next morning it is collected with a special scraper and air dried. Opium collection is a labour-intensive activity. In northern Thailand, the capsules are incised when they change colour from green to slightly grey-green. The harvest period lasts from a few days up to a week after the last petals have dropped from a flower. Tapping is carried out with a special knife, consisting of several sharp blades bound together so that one stroke makes several incisions on the capsule, about 1 mm apart. The lancing and collection is repeated 3-4 times for each capsule in as many days. The capsules are then allowed to mature, and those from the most robust plants are harvested to obtain seed for the next year. The hill tribes of the "Golden Triangle" do not use the seed for food or oil. When the crop is grown for straw extraction, the fruits are harvested after maturity with 10-30 cm of the pedicel attached. The seeds are separated and the straw is used for extraction of alkaloids. The crop can also be harvested about 3 weeks before flowering, giving "green poppy", which is rich in alkaloids but has to be dried quickly.

When grown for seed production, the crop is harvested when the capsules turn yellow-green and the seeds inside rattle.

Yield levels in northern Thailand depend on how frequently poppy has been grown on a given field. In the first year, the yield is high, but it drops the second year, and it is usually not worth planting after the third year. The yield is also influenced by the number and mode of lancing practices. The first lancing gives raw opium with a higher morphine content than subsequent lancings; thus, the raw opium obtained from different lancings is stored separately. Terminal capsules (each plant bears 5-8 capsules) yield opium of considerably higher morphine content than the lateral ones. In India, average yield of raw opium is around 30 kg/ha, but yields as high as 60 kg/ha have been reported. When poppy is grown for seed, seed yields are usually between 1.2 and 1.8 t/ha. High commercial yields are obtained in Tasmania, where average dry matter yield of poppy heads (capsules and seeds) is 2.5 t/ha. In Tasmanian field experiments, 3-4 t/ha of poppy heads have been obtained, and morphine yields of 18-30 kg/ha.

In northern Thailand, the harvested opium is carefully packed in leaves before marketing. In India, the raw opium is stored in metal or earthen pots (perforated at the bottom or placed at a tilt to allow the moisture to drain off) and turned over every 10 days to give it a uniform consistency. After that, it is sun-dried and packed in sacks or jars.

Opium requires careful storage as morphine is quickly decomposed by enzyme activity on exposure to air at 15.5°C. However, storing in sealed containers at 36-37°C gave little loss. Under moist conditions, opium may become covered with mould but this does not seem to affect its morphine content. The total alkaloid content of opium may vary from 5-25%. The opium alkaloids (in particular, morphine and codeine) and their salts may be extracted from either raw opium or poppy straw, the process involving concentration of aqueous extracts to a syrupy consistency, followed by precipitation of alkaloids from concentrated extracts.

When poppies are grown for straw production, the seeds are separated from the capsules and pedicels, which are used for direct alkaloid extraction. Oil is extracted from the seeds by pressing or by solvent extraction of crushed seed.

Cross-pollination is common in P. somniferum, and a crop can contain a wide range of forms. Breeding has mainly been carried out in Europe. Until the 1970s, European breeding work was aimed at increased seed and oil yields as well as high alkaloid contents. The increasing abuse of opiates as heroin has stimulated attempts to reduce illicit traffic in opium by banning cultivation of the opium poppy, and to search for Papaver spp. which do not contain morphine. One of these is P. bracteatum, which lacks an enzyme for the demethylation of thebaine. It produces this alkaloid instead of morphine and codeine, and its content can reach up to 3.5% in the dried capsules. The amount is sufficient for economic production on a large scale; chemical demethylation of thebaine to codeine is relatively simple, demethylation of codeine to morphine, however, is not easy. For P. somniferum, breeding in more recent years has been aimed at creating types with a low morphine content. P. orientale L. and P. bracteatum have been crossed to develop perennial types containing thebaine but no morphine, but the resulting progenies were sterile.

Many varieties, strains and hybrids of ornamental poppy with single and double flowers and some with fringed petals have been raised.

P. somniferum as a medicinal crop has generally declined in importance due to its narcotic reputation and the strict regulations imposed on any such ventures. Only the production of limited quantities of drug for legitimate uses is allowed. This situation is likely to continue for the foreseeable future. Nevertheless, in South-East Asia illegal planting still exists, especially in northern Thailand, Laos and Burma (Myanmar). Opium poppy is a popular cash crop for the hill tribes in these areas. In certain areas, activities may also include illegal processing into morphine and heroin. However, there has recently been a drop in opium production in northern Thailand, mainly due to the efforts of the government to suppress opium poppy cultivation and to develop the inaccessible poppy-growing areas. Cultivation as an ornamental and for the production of edible seeds and seed oil may hold out some prospects but should be monitored closely to prevent abuse. Investigation into the potential of poppy flowers for the production of colouring agent (dye) may be worthwhile.

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• Papaver rhoeas
• Papaver somniferum

• Khozirah Shaari & M. Brink