**2. Geographical distribution**

In India, the main opium cultivating areas are divided into 12 divisions including Madhya Pradesh, Uttar Pradesh and Rajasthan while in other parts minor cultivation is also prac‐ ticed (Figure 2). In Uttar Pradesh, the opium cultivation belt is around Barabanki, Shahja‐ hanpur, Faizabad and Bareilly while Ratlam, Mandsaur and Neemuch in Madhya Pradesh are major opium producing areas. Kota, Chittorgarh and Jhalawar in Rajasthan are the areas producing opium. The opium poppy is distributed in the temperate and subtropical regions of the old world extending from 60° North West Soviet Union whereas the southern limit reach almost the tropics. Legally it is cultivated in India, China, USSR, Egypt, Yugoslavia, Czechoslovakia, Poland, Germany, Netherland, Japan, Argentina, Spain, Bulgaria, Hungary and Poland [4, 5]. India is the largest opium producing and exporting country in the world. Globally the licit opium poppy cultivation is under the strict control of Central Bureau of

16

Narcotics with its headquarter at Vienna, Austria. But at some places illegal cultivation is also being practiced which include Golden Crescent (Iran, Afghanistan and Pakistan) and Golden Triangle (Thailand, Burma, Myanmar). In Afghanistan, illegal cultivation of opium poppy to a large extent is the reason for very high drug trafficking compared with other ille‐ gal cultivating areas. Eleven other countries i.e. Australia, Austria, France, China, Hungary, the Netherlands, Poland, Slovenia, Spain, Turkey and Czech Republic also cultivate opium poppy, but they do not extract gum. They cut the bulb with 8" of the stalk (CPS system) for processing to extract alkaloids (Described earlier).

ages. The seeds of opium poppy are highly nutritious as it contains protein upto 24% and other vital nutrients beneficial for human health. The leaves of the plant are used as vegeta‐ ble in some places in the world. The seed oil of poppy is also important for health point of view due to having high percentage of linoleic acid (68%) which helps in lowering blood cholesterol level in human body and is also used in the treatment of cardiovascular diseases

Red Latex Pink Latex

In India, the main opium cultivating areas are divided into 12 divisions including Madhya Pradesh, Uttar Pradesh and Rajasthan while in other parts minor cultivation is also prac‐ ticed (Figure 2). In Uttar Pradesh, the opium cultivation belt is around Barabanki, Shahja‐ hanpur, Faizabad and Bareilly while Ratlam, Mandsaur and Neemuch in Madhya Pradesh are major opium producing areas. Kota, Chittorgarh and Jhalawar in Rajasthan are the areas producing opium. The opium poppy is distributed in the temperate and subtropical regions of the old world extending from 60° North West Soviet Union whereas the southern limit reach almost the tropics. Legally it is cultivated in India, China, USSR, Egypt, Yugoslavia, Czechoslovakia, Poland, Germany, Netherland, Japan, Argentina, Spain, Bulgaria, Hungary and Poland [4, 5]. India is the largest opium producing and exporting country in the world. Globally the licit opium poppy cultivation is under the strict control of Central Bureau of

16

in human system [2,3].

210 Plant Breeding from Laboratories to Fields

Figure 1. Capsule having brown and pink latex in opium poppy.

**2. Geographical distribution**

**Figure 1.** Capsule having brown and pink latex in opium poppy.

**Figure 2.** Opium cultivating areas in India and different offices of Narcotics Deptt. Cited from: http:// www.uwmc.uwc.edu/academics/departments/political\_science/opiumprod.html#map

#### **3. Economic importance of opium poppy and its derivatives**

Opium poppy belongs to the family Papaveracae and has been attracting the interest of re‐ searchers because of its pharmaceutical, decorative and alimentary attributes. Scientists have been able to identify 2500 different compounds in opium poppy belonging to different biochemical groups used in pharmaceutical industries. Among the various drugs of medici‐ nal importance, opioids are an important class of compounds produced by opium poppy which are used in medicine as a pain reliever. These opioids interact with the opioid recep‐ tor present in the central nervous system and gastro-intestinal tract [6]. However, several of these medicinal compounds can be made synthetically but alkaloids belonging to various groups viz., Phenanthredene (Morphine, Codeine, Thebaine), the true Benzylisoquinilone (Papaverine) and Phthalideisoquinilone (Narcotine) are only obtained from opium which place opium poppy at the highest place among the diverse array of medicinal plants [7]. The most important and potent alkaloid is morphine which can be used for both short term as well as long term pain control, is widely used in many prescriptions of pain medications. The drug occurs as a white crystalline powder or colorless crystals and is available for legal medical use. Recently, scientists at the University of Pennsylvania have noticed complica‐ tion in patient with hepatitis C disease due to withdrawal of morphine as it suppresses IFNalpha-mediated immunity and enhances virus replication. This disease is common among intravenous drug users. Due to the interactive role of morphine with hepatitis C disease, in‐ terest has been developed in determining the effect of drug abuse, especially morphine and heroin on progression of the disease. The discovery of the association between two would certainly help in the treatment of both HCV infection and drug abuse [8]. Morphine is also beneficial for immediate relief in reducing the symptoms of shortness of breath caused due to cancer and non-cancerous incident [9, 10]. Morphine is widely available in market as tab‐ lets, modified release-tablets, capsules, oral liquid and sachets of modified-release oral liq‐ uid, injections and suppository [11]. There are however, many serious side effects of morphine which includes shallow breathing, slow heartbeat, stiff muscles, seizure (convul‐ sions), unusual thoughts or behavior, severe weakness, constipation etc.

Another important alkaloid is codeine which is considered as a prodrug because it is con‐ verted into morphine and codeine-6-glucuronide (C6G) in *in vivo* [12, 13]. Codeine is a natu‐ ral isomer of morphine and is formulated as 3-methyl morphine. In *in vivo* system, 5-10% of codeine is metabolized into morphine, while remaining is left free or in conjugated system as codeine-6-glucuronide (~70%), or it is converted into norcodeine (~10%) and hydromor‐ phone (~1%). Codeine is less effective and has lower dependence-liability than morphine [13]. Similar to all other opioids, continuous use of codeine induces physical dependence and it can be psychologically addictive. However, mild effects are caused due to its with‐ drawal, so is less addictive than other opiates. Codeine is also used as antitussive drug against coughing and widely used in the treatment of severe diarrhea and diarrhea predom‐ inant bowel syndrome. The most frequently used drug forms are "loperamide, diphenoxy‐ late, paregoric and laudanum [14, 15]. In addition to analgesic and antitussive effect there

are some side effects of codeine which includes euphoria, itching, drowsiness, vomiting, or‐ thostatic hypotension, urinary retention, depression and constipation [16]. One of the most serious adverse effects includes respiratory depression [17]. Another alkaloid thebaine is al‐ so produced which is non-narcotic in nature can also be used as an analgesic. It is used for the production of oxycodone and other semi-synthetic analgesic opiates [18, 19]. Higher doses of thebaine cause convulsions similar to that of strychnine poisoning [20]. Another im‐ portant constituent in opium latex is noscapine which is used in relieving cough and head‐ ache. Researchers are continuously investigating of its use in treatment of several cancers and hypoxic ischemia in stroke patients. In the treatment of cancers, noscapine appears to interfere with the functioning of microtubule and thus in division of cancer cells while in treatment of stroke patients, noscapine seems to block the bradykinine β-2 receptors which help in recovery from the disease. Early studies in the treatment of prostate cancer are very promising [21]. Scientists have found a noticeable decrease in mortality in patients treated with noscapine [22]. Noscapine is non-addictive, widely available, has low incidence of side effect and can be easily administered orally, prompting a huge potential for its use in devel‐ oping countries. An important member of Benzylisoquinilone group 'Papaverine' is also an important alkaloid produced by opium poppy. Papaverine is used in the treatment of spasms of the gastrointestinal tract, bile ducts and ureter. It is also used as a cerebral and coronary vasodilator in subarachnoid hemorrhage (combined with balloon angioplasty) and coronary artery bypass surgery [21, 23-25]. Papaverine is also used as an erectile dysfunction drug alone or sometimes in combination with phentolamine [26, 27]. During microsurgery, papaverine is used as a smooth muscle relaxant and is directly applied to blood vessels [28, 29]. It is also applied in cryopreservation of blood vessels along with other glycosaminogly‐ cans and protein suspensions [21, 30]. Papaverine also functions as a vasodilator during cry‐ opreservation when used in conjunction with verapamil, phentolamine, nifedipine, tolazoline or nitroprusside [22, 31]. Scientists are continuously investigating for its use as a topical growth factor in tissue expansion with some success [23]. All these effects of papa‐ verine are attributed to its inhibitory effect on phosphodiesterases [32]. Though papaverine has such extra ordinary attributes but has some common side effects which include poly‐ morphic ventricular tachycardia, constipation, increased transaminase levels, increased al‐ kaline phosphatase levels, somnolence and vertigo. The area under poppy cultivation varied according to the total demand of opium put through the United Nation. India is one of the largest producer and exporter of licit opium and produces about half the opium utilized by the world's pharmaceutical industries.

**3. Economic importance of opium poppy and its derivatives**

212 Plant Breeding from Laboratories to Fields

sions), unusual thoughts or behavior, severe weakness, constipation etc.

Another important alkaloid is codeine which is considered as a prodrug because it is con‐ verted into morphine and codeine-6-glucuronide (C6G) in *in vivo* [12, 13]. Codeine is a natu‐ ral isomer of morphine and is formulated as 3-methyl morphine. In *in vivo* system, 5-10% of codeine is metabolized into morphine, while remaining is left free or in conjugated system as codeine-6-glucuronide (~70%), or it is converted into norcodeine (~10%) and hydromor‐ phone (~1%). Codeine is less effective and has lower dependence-liability than morphine [13]. Similar to all other opioids, continuous use of codeine induces physical dependence and it can be psychologically addictive. However, mild effects are caused due to its with‐ drawal, so is less addictive than other opiates. Codeine is also used as antitussive drug against coughing and widely used in the treatment of severe diarrhea and diarrhea predom‐ inant bowel syndrome. The most frequently used drug forms are "loperamide, diphenoxy‐ late, paregoric and laudanum [14, 15]. In addition to analgesic and antitussive effect there

Opium poppy belongs to the family Papaveracae and has been attracting the interest of re‐ searchers because of its pharmaceutical, decorative and alimentary attributes. Scientists have been able to identify 2500 different compounds in opium poppy belonging to different biochemical groups used in pharmaceutical industries. Among the various drugs of medici‐ nal importance, opioids are an important class of compounds produced by opium poppy which are used in medicine as a pain reliever. These opioids interact with the opioid recep‐ tor present in the central nervous system and gastro-intestinal tract [6]. However, several of these medicinal compounds can be made synthetically but alkaloids belonging to various groups viz., Phenanthredene (Morphine, Codeine, Thebaine), the true Benzylisoquinilone (Papaverine) and Phthalideisoquinilone (Narcotine) are only obtained from opium which place opium poppy at the highest place among the diverse array of medicinal plants [7]. The most important and potent alkaloid is morphine which can be used for both short term as well as long term pain control, is widely used in many prescriptions of pain medications. The drug occurs as a white crystalline powder or colorless crystals and is available for legal medical use. Recently, scientists at the University of Pennsylvania have noticed complica‐ tion in patient with hepatitis C disease due to withdrawal of morphine as it suppresses IFNalpha-mediated immunity and enhances virus replication. This disease is common among intravenous drug users. Due to the interactive role of morphine with hepatitis C disease, in‐ terest has been developed in determining the effect of drug abuse, especially morphine and heroin on progression of the disease. The discovery of the association between two would certainly help in the treatment of both HCV infection and drug abuse [8]. Morphine is also beneficial for immediate relief in reducing the symptoms of shortness of breath caused due to cancer and non-cancerous incident [9, 10]. Morphine is widely available in market as tab‐ lets, modified release-tablets, capsules, oral liquid and sachets of modified-release oral liq‐ uid, injections and suppository [11]. There are however, many serious side effects of morphine which includes shallow breathing, slow heartbeat, stiff muscles, seizure (convul‐

> Keeping in mind, the enormous importance of opium poppy among the diverse array of me‐ dicinal plants, researchers were encouraged to work for its genetical improvement. Re‐ searchers engaged in opium poppy researches are continuously working to develop designer plants having all specific alkaloids in latex in large quantities. Previously, both con‐ ventional and molecular approaches have been applied to develop varieties rich in specific alkaloids. This chapter deals a detailed account (in different subheadings) of the convention‐ al breeding techniques applied to upgrade the latex and alkaloid status along with its nutri‐ tional content in opium poppy.
