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Papaver somniferum (opium poppy) is one of the world's oldest medicinal plants which are widely used for medicinal, nutritive and scientific purposes. Turkey is one of the major legal opium poppy producer countries in the world and the seed paste of the poppies is consumed in great deal, even more than 100g per meal. The main objective of this study is to investigate the influence of poppy seed paste ingestion on urine tests for opiates whether or not could lead to opiate positive urine test results. For this purpose, a variety of poppies were used and the morphine content of white, yellow and blue-black poppies were determined as 1.9, 4.0 and 2.6mg/kg, respectively. 100g of these seed pastes were consumed in the breakfast by ten healthy adults enrolled in the study over three days and urine samples were collected before and after the breakfast. Opiate screening analysis was carried out by enzyme immunoassay method and the results were evaluated by two different cut-off values (300 and 2000ng/mL). Morphine confirmation analysis was made by GC-MS system and the chromatographic method was validated in terms of selectivity, extraction efficiency, linearity (25-2000ng/ml), intra-assay precision, accuracy, limit of detection (LOD) and limit of quantitation (LOQ) (3 and 10ng/ml), carryover, matrix effect, dilution integrity and stability. According to cut-off value 300ng/ml, opiate concentrations were found positive up to 48h. For cut-off value 2000ng/mL; this time was up to 12h in collected urine samples after consumption of three different colored poppy seed pastes. In all urine samples, thebaine was detected while the heroin abuse metabolite 6-acetyl morphine (6-AM) was not. Urine drug testing legislation was revised on 2016 in Turkey and opiate screening cut-off values increased from 300 to 2000ng/mL. Overall results have shown that poppy seed paste as food consumption could lead to opiate positive urine test result even if increased cut off levels are used. It can also be deduced that thebaine can be taken as supportive biomarker for poppy seed paste consumption. Awareness of interpretation of urine test results and defining the procedures especially for forensic drug testing must be done in legal aspect to ensure justice for each individual (workplace, traffic, court etc.)., (Copyright © 2018. Published by Elsevier B.V.)

The cultivation of opium poppy is the only commercially viable source of most morphinan alkaloids. Bioproduction of morphinan alkaloids in recombinant whole-cell systems provides a promising alternate source of these valuable compounds. The enzyme codeine 3-O-demethylase can transform morphinan alkaloids by O-demethylation and has been applied in single step biotransformation reactions or as part of larger biosynthetic cascade, however, the productivity for these reactions remains low and suboptimal enzyme properties could be improved. This mutagenesis study targeted non-conserved N-and C-terminal residues, which were replaced with the equivalent residues from enzyme thebaine 6-O-demethylase. Whole cell biotransformation performance was significantly improved in Escherichia coli expressing codeine 3-O-demethylase mutants, with a ~ 2.8-fold increase in the production of oripavine from thebaine and ~ 1.3-fold increase in the production of morphine from codeine. Statistical analysis of biotransformation yield, enzyme expression and stability, predicted using changes in Gibbs free energy (ΔΔG) with deep-learning-based model DDmut, suggested that altered enzyme stability and/or expression of soluble protein may contribute to the observed improvements in biotransformation. This approach could be beneficial for screening future codeine 3-O-demethylase mutations and for other enzymes. [ABSTRACT FROM AUTHOR]

Opium poppy is a plant used in both the pharmaceutical and food industries. Substances found on the surface of dry poppy seeds belong to the group of opium alkaloids. However, the presence of these substances in food products poses a risk to consumer health, which is why new permissible levels for both substances in poppy seeds and derivative products have been introduced in Regulation (EU) 2023/915. This research aimed to analyze the content of all six opium alkaloids in poppy seeds provided directly by producers as well as those available on the local market in Poland. The research confirmed the presence of morphine in all examined poppy seed samples. The alkaloid content ranged from 12.46 to 102.86 mg/kg for seeds purchased in local markets and from 1.1 to 110.1 mg/kg for seeds obtained directly from producers. Both groups showed similar levels of morphine content as well as other OAs, which significantly exceeded the permissible limit of 20 mg/kg set by the European Commission (EU) 2023/915. These results indicate that the presence of morphine and other opium alkaloids in poppy seeds exceeds permissible levels, posing a serious health issue and necessitating further research and improvement in processing methods. [ABSTRACT FROM AUTHOR]

Objective The present study was performed to investigate the effect of salicylic acid at different times on the expression of three genes involved in the morphine production end pathway (T6ODM, COR and CODM) in Opium Poppy capsules. It should be noted that these genes play an important role in the production of morphine as a medicinal alkaloid. Materials and methods Seeds of Papaver Somniferum were grown in pots under greenhouse conditions. When the plants reached the flowering stage, two to three days after the petals fell; a superficial scratch was created in the plant capsule and then treated with salicylic acid at a concentration of 50 μM. Capsule sampling was performed at three times zero (a few minutes after spraying salicylic acid solution on the capsule), three and 12 hours after salicylic acid treatment, compared to the control plant. RNA was extracted from the capsule samples, followed by cDNA, and finally the results obtained by qRT-PCR were analyzed using GenEX software. Results The results of this study showed that with increasing the time after treatment of the capsules with salicylic acid, the expression level of all three genes decreased compared to the control plant. The expression of T6ODM gene at zero time increased about 1.84 times the expression of gene compared to the control plant, but the expression of this gene at 3 and 12 hours decreased by 46% and 21%, respectively, compared to the gene expression in the control plant. The results also showed that the expression of COR gene increased by about 1.26 times in zero hours compared to the control plant and decreased by 15% in three hours and by almost 30% in 12 hours compared to the control plant. . The expression level of CODM gene at zero hours was almost equal to that of the control plant and at three and 12 hours their expression level was almost zero. Also, the graphs related to T6ODM, CODM and COR genes showed that there is a significant difference in terms of gene expression between different times in each gene. Conclusions It is generally inferred that salicylic acid treatment reduces the expression of the three end genes involved in the morphine production pathway by increasing the time from zero hours to 12 hours. [ABSTRACT FROM AUTHOR]

The goal of this study was to clarify the role of capsule size and morphology in the alkaloid yield of poppy. In 2023, two industrial varieties from large-scale cultivation were investigated. Three classes of capsule size (large, medium, and small) and four organelles (wall, placenta, disc, and thalamus) of the seedless capsule were studied for their mass proportions and alkaloid contents. In 'Meara', large capsules had 41% lower total alkaloid levels than smaller ones. In 'Morgana', there was no difference in total alkaloids between size groups, but large capsules had higher contents of codeine and thebaine. Among the four organelles, the wall represented the largest mass in both varieties (60–67%), while the disc and the thalamus gave the lowest proportions (below 9%). In the variety 'Meara', the highest alkaloid contents appeared in the wall (2.69% d.w.), followed by the placenta, and the other two parts. 'Morgana' accumulated the highest alkaloid content (3.72% d.w.) in the placenta. Morphine follows the trend of the total content, while codeine and thebaine may differ. Accurate information on the accumulation of alkaloids in the generative organs may contribute to increasing effectiveness in target-oriented breeding and optimization of cultivation with an appropriate choice of variety. [ABSTRACT FROM AUTHOR]

The opium poppy's ability to produce various alkaloids is both useful and problematic. Breeding of new varieties with varying alkaloid content is therefore an important task. In this paper, the breeding technology of new low morphine poppy genotypes, based on a combination of a TILLING approach and single-molecule real-time NGS sequencing, is presented. Verification of the mutants in the TILLING population was obtained using RT-PCR and HPLC methods. Only three of the single-copy genes of the morphine pathway among the eleven genes were used for the identification of mutant genotypes. Point mutations were obtained only in one gene (CNMT) while an insertion was obtained in the other (SalAT). Only a few expected transition SNPs from G:C to A:T were obtained. In the low morphine mutant genotype, the production of morphine was decreased to 0.1% from 1.4% in the original variety. A comprehensive description of the breeding process, a basic characterization of the main alkaloid content, and a gene expression profile for the main alkaloid-producing genes is provided. Difficulties with the TILLING approach are also described and discussed. [ABSTRACT FROM AUTHOR]

Opioids have been used for thousands of years for the treatment of pain. Records on papyri in Ancient Egypt reported the use of opium to relieve pain. In 1973, Candace Pert used radioactive morphine to assess its place of action and, surprisingly, found that the drug attaches to specific areas of the brain, namely on receptors called “morphine receptors”. Because animal model studies have debunked that a receptor would not be needed for the alkaloid in the Papaver somniferum plant, this finding sparked a search for the molecule that would endogenously stimulate that receptor, culminating in the discovery of “endogenous opiopeptides” or “endorphins” by John Hughes and Hans Kosterlitz in 1975. Most clinically relevant opioids operate at the level of the “morphine receptor” or “μ receptors”, and are therefore considered “agonists μ”. This paper looks at opioids in an effort to better understand the side effects and drug interactions. [ABSTRACT FROM AUTHOR]

The urine toxicology screen is a test widely used in clinical practice, but it may be subject to false positive or negative results. With regard to opioid screen, one of the causes of false positives is the ingestion of poppy seeds. The authors describe the case of an adolescent who performed a urine toxicology screen in the context of a first seizure episode, which revealed the presence of morphine. After a detailed anamnesis, the teenager reported having consumed crackers with poppy seeds the night before. The opium poppy is widely used in the food industry, mainly through its seeds. This clinical case alerts us to the possibility of false positives in toxic screening tests after ingesting poppy seeds. This situation can be a problem as it can have medical-legal implications. For this reason, the cut-off value of 300 ng/ml used by most laboratories in many countries has been frequently discussed. [ABSTRACT FROM AUTHOR]

Poppy (Papaver somniferum) L. is cultivated commercially in several countries legally to produce alkaloids (i.e. morphine, codeine, thebaine, narcotine, papaverine and oripavine) for pharmaceutical industries. The demand for these alkaloids is increasing and Global climate change is influencing poppy cultivated areas. Turkiye is responsible for poppy cultivation, breeding new cultivars and adaptation trials. Therefore, the present investigation was undertaken during two years to examine the most cultivated 16 cultivars and 3 new lines for capsule morphology properties, their alkaloid values and capsule yield in Ankara conditions which is not in the poppy cultivation area in Turkiye. The experiment was arranged in the randomized complete block design with four replications. The plot size of 2.4 m² (2 m × 1.2 m) and 4 rows with spacing 30 cm between rows and 10 cm within plants were applied. The capsule parameters and alkaloid content were measured in 10 dry capsules after harvesting. To measure the content of alkaloids (%) the capsules were ground into powder and HPLC-MS/MS analysis after the solvent extraction of poppy straw on dry matter was conducted. Genotypes showed variation in stigmatic rays and the number of stigmatic rays was higher in the first year. The maximum stigmatic ray value was seen in cv. Ofis-95 with 13.27 in the first year. The maximum value for capsule length and diameter was obtained from cv. Ofis-NP (51.75 mm) and cv. Ofis-95 (45.00 mm) in the mean of two years. The maximum capsule yield was obtained from cv. Ofis-95 for both years and the values were 155.90 and 160.30 kg da-1. The maximum morphine percentage was recorded in cv. Ofis-1 with 1.63 and 1.24% respectively. The percentage of noscapine, codeine, thebaine was noted as maximum values in Ofis-1 among genotypes. The results favoured the cultivation of these genotypes in Ankara which is not one of the poppy cultivation area and further agronomic studies should be undertaken to develop production technology of poppy in these environmental conditions. [ABSTRACT FROM AUTHOR]

Background: The poppy seeds commonly known as ‘khus-khus’ or ‘postadana’, obtained from opium poppy plant (Papaver somniferum L.) is known one of the world’s oldest medicinal plant. Its alkaloids, seeds and oil used since time immemorial for therapeutic, food stuffs and economical purpose. An effective breeding program plays an important role for selection, genetic improvement and development of high yielding cultivars/variety in opium poppy. Therefore, a study was conceded out to evaluate the genetic variability, path analysis for different agronomic traits along with their major chemical constituents of opium alkaloids in 30 accessions/landraces of opium poppy (Papaver somniferum L.) collected from different geographical places of India. Methods: The 30 genotypes of Opium poppy including different breeding lines and landraces collected from different places were grown in year (2017-18) in randomized complete-block designs (RCBD) with three replications at the research farm of CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow. Morpho-metric data were recorded on five competitive randomly selected plants in each line for following thirteen traits. Dried husk/straw capsules were chemically analyzed through HPLC. The pooled mean data were statistically analysed by using Windostat statistical software 4.0 versions available at Department of Genetics and Plant Breeding, CSIR-CIMAP Lucknow. Result: Variation among the mean of thirty diverse genetic stocks was highly significant (p<0.01) for all thirteen traits. High heritability coupled with high Genetic advance as percent mean (GAM) and Genotypic coefficient of variation (GCV) for the traits Thebaine and Nosacapine. The results of associations studies revealed that the trait capsule/plant was positively and significantly correlated with seed (g)yield/plant (gm) and nosacapine at both genotypic and phenotypic level. According to results, a significant genetic variability was also present among 30 accessions, simple selection can be employed to improve seed yield along with alkaloids yield. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the proportions of morphine, thebaine, noscapine, codeine, oripavine and papaverine alkaloids in poppy varieties and hybrids. Nine parents and 36 hybrid lines were used in the trial. The trial was carried out in 2016 and 2017 in four replications according to the Randomized Block Trial Design. According to the average results of the two years, in parent and hybrid combinations, morphine was found to vary between 0.42% and 1.66%, thebaine between 0.01% and 0.53%, noscapine between 0.01% and 0.31%, codeine between 0.03% and 0.17%, oripavine between 0.00% and 0.12% and papaverine between 0.00% and 0.10%. In the study, Ofis NM x Ofis 1, Ofis 1 x TMO T, Ofis 2 x TMO T, Ofis NM x Ofis 1, Ofis NM x TMO T hybrid combinations were identified as superior hybrids compared to the others. [ABSTRACT FROM AUTHOR]

Objective: Czech Republic belongs among the biggest world producers of poppy seeds. Poppy seeds are used in medicine and are part of traditional food. This plant contains several alkaloids including morphine and codeine. The aim of our study was to investigate whether opiates can be detected in urine samples after single ingestion of poppy seeds in cakes in a group of volunteers. Design: prospective trial Settings: Psychiatric a psychotherapeutic out-patient department, Slovanska 69, Plzen, MedAvante Inc., Smrkova 23, Plzen and Department of Clinical Biochemistry and Haematology, Faculty of Medicine, Charles University and University Hospital, Pilsen, Czech Republic Material and Methods: We examined opiates with a qualitative and semiquantitative method in urine samples of 14 volunteers 15 hours after ingestion of a definitive amount of poppy seeds in home-made cakes. Correlation between amount of ingested poppy seeds and concentration of opiates in urine was observed. Results: In 12 volunteers opiates in urine were detected by a qualitative immunochemical test 15 hours after poppy seeds ingestion. Using a semiquantitative immunochemical method, a significant correlation between opiates concentration in urine (after correction for urine creatinine) and amount of ingested poppy seeds was found. In two persons concentration of opiates in urine exceeded 300 µg/L; this concentration is considered positive when testing opiate-addicted persons. Conclusion: On the basis of the study results and a case of a patient with unconsciousness and a positive finding of opiates in urine we can conclude that preceding ingestion of poppy seeds in diet must be taken into account when evaluating this laboratory finding. [ABSTRACT FROM AUTHOR]

In recent years, following intoxications and false positive drug tests for poppy seeds, dangerously high concentrations of opium alkaloids (OAs) have been found. For this reason, health authorities are demanding studies to establish effective practices to reduce OAs in these seeds. Grinding, a common culinary process for various recipes, has previously been associated with potential morphine degradation. However, these studies have not established effective grinding conditions to decrease the concentration of all main OAs. Furthermore, due to the large variation in OAs concentration that can occur even in the same bag, this can be a difficult task. In view of the above, this study aimed to evaluate for the first time the impact of different grinding types, varying grinding time or repetitions, to determine any degradation trends of the main OAs present in poppy seeds. As a result, it was obtained a notable 20% degradation of morphine in the second grinding with grinders where the oil content of the seeds is not released, hinting at oil's protective role against morphine oxidation. Therefore, the choice of grinding method is crucial. However, while acknowledging this, relying solely on this method as a good practice for OAs reduction may be insufficient, as it seems to have minimal impact on other OAs with any of the tested methods and conditions. [Display omitted] • Grinding should not be a good practice for OAs reduction in poppy seeds. • Grinding types that extract oil do not exhibit degradation of OAs in poppy seeds. • Morphine is the only alkaloid that exhibits a small reduction with grinding. • Longer grinding time did not result in a degradation trend of OAs. [ABSTRACT FROM AUTHOR]

Secondary metabolite biosynthesis in medicinal plants is multi-step cascade known to be modulated by associated endophytes. While a single endophyte is not able to upregulate all biosynthetic steps, limiting maximum yield achievement. Therefore to compliment the deficient characteristics in an endophyte we tried consortium of endophytes to achieve maximum yield. Here, efforts were made to maximize the in planta morphine yield, using consortium of two endophytes; SM1B (Acinetobacter sp.) upregulating most of the genes of morphine biosynthesis except T6ODM and CODM , and SM3B (Marmoricola sp.) upregulating T6ODM and CODM in alkaloid-less Papaver somniferum cv. Sujata. Consortium-inoculation significantly increased morphine and thebaine content, and also increased the photosynthetic efficiency of poppy plants resulted in increased biomass, capsule weight, and seed yields compared to single-inoculation. The increment in morphine content was due to the modulation of metabolic-flow of key intermediates including reticuline and thebaine, via upregulating pertinent biosynthetic genes and enhanced expression of COR , key gene for morphine biosynthesis. This is the first report demonstrating the endophytic-consortium complimenting the functional deficiency of one endophyte by another for upregulating multiple genes of a metabolic pathway similar to transgenics (overexpressing multiple genes) for obtaining enhanced yield of pharmaceutically important metabolites. [ABSTRACT FROM AUTHOR]

This study assesses the morphine content of different preparations of poppy seed tea using an acidic potassium permanganate chemiluminescence detection method. Four 'model' teas were prepared utilizing extractants commonly described in online drug forums and compared with a 'control' solution containing acetic acid. High performance liquid chromatography, coupled with acidic potassium permanganate chemiluminescence detection, was able to determine that significant concentrations of morphine can be extracted from the culinary poppy seeds with all four tea extractants (between 155 µg/g and 223 µg/g). The results of this study provide a process of determining the presence of morphine in a range of different poppy seed tea extracts in a fast, efficient and selective manner. This protocol will afford better understanding of the extent of poppy seed tea extracts in the community and allow for extension of forensic practice. [ABSTRACT FROM AUTHOR]

Summary: Codeinone reductase (COR) catalyzes the reversible NADPH‐dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). It also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3‐O‐demethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, the formation of neomorphine by COR is irreversible. Neopine is a minor substrate for codeine O‐demethylase (CODM), yielding morphine. In the plant, neopine levels are low and neomorphine has not been detected. Silencing of CODM leads to accumulation of upstream metabolites, such as codeine and thebaine, but does not result in a shift towards higher relative concentrations of neopine, suggesting a mechanism in the plant for limiting neopine production. In yeast (Saccharomyces cerevisiae) engineered to produce opiate alkaloids, the catalytic properties of COR lead to accumulation of neopine and neomorphine as major products. An isoform (COR‐B) was isolated from opium poppy chemotype Bea's Choice that showed higher catalytic activity than previously characterized CORs, and it yielded mostly neopine in vitro and in engineered yeast. Five catalytically distinct COR isoforms (COR1.1–1.4 and COR‐B) were used to determine sequence–function relationships that influence product selectivity. Biochemical characterization and site‐directed mutagenesis of native COR isoforms identified four residues (V25, K41, F129 and W279) that affected protein stability, reaction velocity, and product selectivity and output. Improvement of COR performance coupled with an ability to guide pathway flux is necessary to facilitate commercial production of opiate alkaloids in engineered microorganisms. [ABSTRACT FROM AUTHOR]

Poppy ( Papaver somniferum) is a traditional source of isoquinoline alkaloids, especially morphine, codeine and papaverine that exhibit a wide spectrum of therapeutic effects. Due to beneficial properties, poppy has been used by humankind for several thousand years and is still being used around the world. The present study was aimed to investigate alkaloid composition and biological activity of various parts of the plant (leaves, stems, roots, capsules, flowers, seeds) in an ornamental variety of P. somniferum. The alkaloid content rangedwithin 0.16 - 6.5 mg/g fresh weight of raw plant material. The major components of the alkaloid fraction were papaverine (37.7 - 2062.9 μg/g), codeine (7.4 - 1280.5 μg/g) and morphine (3.25 - 929.3 μg/g). The P. somniferum alkaloid extract produced a strong antioxidant effect, which was evaluated using the radical-scavenging DPPH, ABTS and FRAP assays. The antioxidant properties were characterized by IC values ranging within 35.1 - 157.6 μg/mL for DPPH radical and 138.5 - 306.3 μg/mL for ABTS∙ radical scavenging. The ferric reducing antioxidant power (FRAP) values varied from 59.75 to 1348.71 mM FeSO/g extract. The alkaloid extract was active against all human tumor cell lines studied (HeLa, Caco-2, MCF-7, CCRF-CEM and CEM/ADR 5000). The methanol extract exhibited a pronounced cytotoxicity against most of cancer cell lines studied, especially those with a low expression of ABC transporters. [ABSTRACT FROM AUTHOR]

Opium poppy is an important medicinal plant because of its very valuable pharmaceutical alkaloids such as morphine, codeine, and papaverine, etc. The research was carried out with the aim to examining the relationships between capsule yield, some other yield and quality traits by means of correlation, path and principal components analysis (PCA) in fifteen opium poppy (Papaver somniferum L.) cultivars registered in Turkey. The experiments were conducted designed according to a randomized complete block with three replications during 2012/13 and 2013/14 growing years in Isparta conditions. In the research, there were significant positive correlations between capsule yield and capsule width, and 1000 seed weight, while insignificant associations between capsule yield (non-seed) and seed yield, plant height, capsule number, capsule length, oil yield, and morphine content were determined. The significant and high negative correlation was determined between capsule yield with oil content. According to the path analysis, the highest positive direct effect on capsule yield was seed yield (48.202%), and the highest positive indirect effect on capsule yield was capsule width (47.877%) via seed yield. The ten PCA components (PC1 to PC10) created 90.09% of the total variation among traits in poppy cultivars. PC1, PC2, PC3, and PC4 with values of 52.0%, 16.9%, 11.8%, and 10.2%, respectively contributed to the total PCA value, and plant height, capsule width, capsule number, and 1000 seed weight were found to be effective components on the yield in PCA analysis. The bi-plot analysis showed that capsule number, capsule length, seed yield, and oil yield created the same group and plant height and capsule width were another group, and these characters showed stability for the cultivars. The according to the results of the correlation, path, and PCA, capsule width and 1000 seed weight were effective components on capsule and seed yields of the opium poppy. [ABSTRACT FROM AUTHOR]

Benzylisoquinoline alkaloids (BIAs) are important secondary plant metabolites and include medicinally relevant drugs, such as morphine or codeine. As the de novo synthesis of BIA backbones is (still) unfeasible, to date the opium poppy plant Papaver somniferum L. represents the main source of BIAs. The formation of BIAs is induced in poppy plants by stress conditions, such as wounding or salt treatment; however, the details about regulatory processes controlling BIA formation in opium poppy are not well studied. Environmental stresses, such as wounding or salinization, are transduced in plants by phospholipid-based signaling pathways, which involve different classes of phospholipases. Here we investigate whether pharmacological inhibition of phospholipase A 2 (PLA 2 , inhibited by aristolochic acid (AA)) or phospholipase D (PLD; inhibited by 5-fluoro-2-indolyl des-chlorohalopemide (FIPI)) in poppy plants influences wound-induced BIA accumulation and the expression of key biosynthetic genes. We show that inhibition of PLA 2 results in increased morphinan biosynthesis concomitant with reduced production of BIAs of the papaverine branch, whereas inhibition of PLD results in increased production of BIAs of the noscapine branch. The data suggest that phospholipid-dependent signaling pathways contribute to the activation of morphine biosynthesis at the expense of the production of other BIAs in poppy plants. A better understanding of the effectors and the principles of regulation of alkaloid biosynthesis might be the basis for the future genetic modification of opium poppy to optimize BIA production. [ABSTRACT FROM AUTHOR]

Combining ability studies for eight parents and their all possible crosses (excluding reciprocals) of opium poppy were grown at experimental farm of Plant Breeding and Genetics, Rajasthan College of Agriculture, Maharana Pratap University of Agriculture and Technology, Udaipur (Rajasthan). This experiment was conducted in random block design with three replications and estimate combining ability for latex yield and yield related traits. Combining ability analysis indicated that mean square due to gca and sca were significant for all the characters, expect for plant height for sca, indicating the importance of both additive as well as non-additive genetic effect for the inheritance of all the characters under pooled over environments. Parents UOP-69, UOP-80 and UOP-99 were good general combiners for most of the important characters specially latex yield per plant, seed yield per plant, effective capsules per plant, seed harvest index and morphine content in pooled over the environments. The parent UOP-53 was also good general combiner for morphine content. The parent UOP-79 possessed good nicking ability for earliness and short plant stature. On pooled basis, the hybrids UOP-80 x UOP-20, UOP-53 x UOP-1185, UOP-79 x UOP-60, UOP-79 x UOP-20, UOP-79 x UOP-1185 and UOP-80 x UOP-1185 also showed high SCA effect for latex, seed and husk yield per plant, it could be used for exploitation of heterosis for latex yield potential and other related traits. [ABSTRACT FROM AUTHOR]

The goal of this study was to characterize forty genotypes of Papaver somniferum L. and assess the genetic variability using data from morphological as well as biochemical studies. For the characterization, the morphological characters viz., plant height, primary branch, peduncle length, days to maturity, number of selfed-capsules, weight of selfed-capsule, number of open-pollinated capsule, weight of open pollinated capsule were complimented with five biochemical alkalodis morphine, codeine, thebaine, papaverine and narcotine. The results show that morphine and codeine had highly significant positive correlation (0.68 **). Similarly, a highly positive significant correlation (0.63 **) was established between morphine and narcotine. Further, all the 40 genotypes were subjected to cluster analysis where eight primary clusters were obtained using morphological analysis, whereas nine clusters were formed based on biochemical analysis. On the basis of morphological analysis, 32 genotypes were assigned to a one, large cluster which was further organized into 12 sub-clusters. However, clustering based on biochemical analysis yielded one, large cluster with 25 genotypes, which was further subdivided into eight subclusters. The findings from the present study can be successfully employed for developing superior lines of opium poppy. • Correlation studies revealed insights to correlate traits that affect yield directly or indirectly in opium poppy. • Correlation studies help accelerate the process of selection, instantly discarding undesirable genotypes. • Conversion of codeine into morphine occurs as the plant ages. • Narcotine, morphine and codeine accumulation is high when papaverine accumulation has ceased or slowed down. • Direct and indirect selection of strongly correlated traits with the desired parameter can be utilised for enhancing yield in opium poppy. [ABSTRACT FROM AUTHOR]

The alkaloid content in industrial opium poppies (Papaver somniferum L.) has been studied by numerous authors, but not in ornamental cultivars. The aim of the study was to investigate the content of morphine, codeine, and papaverine in P. somniferum cultivars by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). The studied poppy capsules were either grown from the ornamental poppy seeds purchased from different vendors or were unknown cultivars from home gardens in Estonia, cultivated as ornamental poppies. All dried capsules samples (n = 34) contained on average 362 mg/100g of morphine, 25 mg/100g of codeine, and 29 mg/100g of papaverine as determined by CE. The content of morphine determined by HPLC was 152-676 mg/100g, which is a remarkably high concentration allowing potential illegal use of ornamental poppies. Both analytical methods demonstrated similar results. Hence, CE is a suitable alternative to HPLC for quantitative analysis of opium alkaloids as it simplifies the sample preparation procedure. [ABSTRACT FROM AUTHOR]

A method of high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was developed for simultaneous determination of the residues of five opium poppy husk alkaloids in foods, such as morphine, codeine, tibane, papaverine and narcotinum. The samples were extracted by methanol (containing 5% ammonia acetate), and then analyzed by HPLC-MS/MS. The separation was carried out by a Capcell PAK C18 TYPE MGⅡ(5 μm×2.0 mm×150 mm) column, with 10 mmol/L ammonium acetate (pH 4.2) and acetonitrile as mobile phases at a flow rate of 0.2 mL/min. Multiple reaction monitoring (MRM) mode was applied, with positive ion electrospray ionization (ESI). Sample matrix-matched calibration was used to determine the residue contents by external standard. Under the optimized detection conditions, the linear ranges for morphine and codeine are 1.0-20.0 μg/L, and for tibane, papaverine and narcotinum are 0.2-4.0 μg/L, the linear correlation coefficients are all more than 0.999. The limits of quantification for morphine, codeine, tibane, papaverine and narcotinum are 7.5, 7.5, 1.5, 1.5 and 1.5 μg/kg, respectively. The recoveries of five opium poppy husk alkaloids range from 72.2% to 111.4% with the relative standard deviations (RSD) of 3.1%-8.8%. This method is simple, effective and sensitive, which is suitable for the determination and confirmation of five opium poppy husk alkaloids added in the foods illegally. [ABSTRACT FROM AUTHOR]

Main conclusion: Endophytes reside in different parts of the poppy plant and perform the tissue-specific functions. Most leaf endophytes modulate photosynthetic efficiency, plant growth, and productivity while capsule endophytes modulate alkaloid biosynthesis. Endophytes promote plant growth, provide protection from environmental stresses and are the source of important secondary metabolites. Here, we established that the endophytes of opium poppy Papaver somniferum L. may play a role in the modulation of plant productivity and benzylisoquinoline alkaloid (BIA) biosynthesis. A total of 22 endophytes isolated from leaves, roots, capsules and seeds of the poppy plants were identified. Isolated endophytes were used to inoculate the endophytes free poppy seeds and screened for their ability to improve plant productivity and BIA production. It was evident that the endophytes from leaf were involved in improving photosynthetic efficiency, and thus crop growth and yield and the endophytes from capsule were involved in enhancing BIA biosynthesis. Capsule endophytes of alkaloid-rich P. somniferum cv. Sampada enhanced BIA production even in alkaloid-less cv. Sujata. Expression study of the genes involved in BIA biosynthesis conferred the differential regulation of their expression in the presence of capsule endophytes. The capsule endophyte SM1B ( Acinetobacter) upregulated the expression of the key genes for the BIA biosynthesis except thebaine 6- O-demethylase ( T6ODM) and codeine O-demethylase ( CODM). On the other hand, another capsule endophyte SM3B ( Marmoricola sp.) could upregulate both T6ODM and CODM. Colonization of poppy plant by endophytes isolated from leaves, roots and capsules found to be higher in their respective plant parts confirmed their tissue-specific role. Overall, the results demonstrate the specific role of endophytes in the modulation of host plant productivity and BIA production. [ABSTRACT FROM AUTHOR]

The study was carried out in the years 2013 and 2014 at the Łagiewniki farm to determine the effect of some herbicides on the yield and development of two opium poppy cultivars: 'Lazur' - with high morphine content, and 'Borowski Biały' - with low morphine content. The development and yield of the poppy was a derivative of environmental and agronomic conditions. The mixture of tembotrione and fluroxypyr applied post-emergence at a rate of 88 and 75 g a.i. . ha-1, respectively, effectively controlled most weeds which are harmful for the poppy and did not phytotoxically affect opium poppy plants. The level of yield also depended on the cultivar's ability to grow under unfavourable weather conditions. A lower yield was noted for the cultivar with a lower content of morphine - 'Borowski Biały'. [ABSTRACT FROM AUTHOR]

In this study, amount of morphine from poppy capsules (Papaver somniferum) was investigated using ultrasonic assisted extraction (UAE). Response surface methodology was used to estimate effective experimental conditions on the content extraction of poppy capsules. For this purpose, solvent/solid ratio (10–20 mL/500 mg sample), pH (1–13), time (30–60 min), and temperature (30–50°C) were chosen as experimental variables. The affected response is extraction recovery values for morphine from poppy straw. For interpreting the relationship between experimental factors and response, a design table was established with combinations of three different concentrations levels of this compound in 29 trials. The second order quadratic model gave a satisfactory description of the experimental data. In our study, R-Squared (0.96), Adj-R-Squared (0.92), and Pred R-Squared (0.78) values for extraction yield display good accuracy of the derived model. The predicted optimal conditions for the highest morphine level (3.38 mg morphine/500 mg-sample) were found at 19.99 mL solvent/500 mg solid ratio, 59.94 min extraction time, 1.10 pH, and 42.36°C temperature. In the optimal extraction conditions, the experimental values are very close to the predicted values. Consequently, the response surface modeling can be achieved sufficiently to predict extraction yield from poppy straw by ultrasound assisted extraction. [ABSTRACT FROM AUTHOR]

To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (⩾50 °C) was observed in A3, pH increased 16.9–17.54%, total carbon content decreased 15.5–22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P 2 O 5 and K 2 O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. [ABSTRACT FROM AUTHOR]

Papaver somniferum produces therapeutically useful benzylisoquinoline alkaloids (BIAs) like papaverine, thebaine, codeine, and morphine that accumulate in its capsular latex. Morphine is a potent analgesic but is also abused as a narcotic, which has increased the demand for non-narcotic thebaine that can be converted into various analgesics. To curtail the narcotic menace, many distinct genotypes of the plant have been developed that are deficient in morphine and/or latex. Sujata is one such latex-less low alkaloid-producing variety developed from the alkaloid-rich gum harvest variety Sampada. Its utility for gene prospecting and studying differential gene regulation responsible for its low alkaloid, nutritive seed oil, and latex-less phenotype has been exploited in this study. BIA profiling of Sujata and Sampada capsules at the early and late stages indicated that except for thebaine, Sujata had a depressed alkaloid phenotype as compared to Sampada. Comparative transcript-based analysis of the two genotypes was carried out in the early stage capsule (higher thebaine) using subtractive hybridization and microarray. Interrogation of a P. somniferum array yielded many differentially expressing transcripts. Their homology-based annotation classified them into categories-latex related, oil/lipid related, alkaloid related, cell wall related, and others. These leads will be useful to characterize the highly sought after Sujata phenotype. [ABSTRACT FROM AUTHOR]

In November 2013, the UN's Afghanistan Opium Survey reported a 36 per cent rise in opium poppy cultivation, with opium production up by almost half since 2012. This situation has long been recognised as a security threat, with effective programmes to address the complex links between opium trafficking, organised crime and insecurity in Afghanistan more important than ever given the transfer of responsibility for security and governance, by the end of 2014, to the Afghan government. David Bewley-Taylor questions the current focus of counter-narcotics policies and highlights the key challenges likely to impede the reduction of organised crime in Afghanistan post-2014. [ABSTRACT FROM AUTHOR]

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]-phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. [ABSTRACT FROM AUTHOR]

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type–specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O -demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy. [ABSTRACT FROM AUTHOR]

Abstract: A Gram-negative bacterium transforming codeine 1a to 14-hydroxycodeine 1c was isolated from the sample of composted wastes of Papaver somniferum deposited in a factory producing poppy seed. Based on 16S ribosomal RNA gene phylogeny, biochemical and morphological properties, the strain was designated as Rhizobium radiobacter R89-1. The bacterium is able to transform 1a into four C-14-hydroxy derivatives of codeine. When used as a whole-cell catalyst, 100% conversion was achieved at concentration of 1a up to 6.0g/L to 14-hydroxycodeine 1c as a single product. Biohydroxylation of codeine to C-14-hydroxy derivatives, a high tolerance of the strain to 1a and activity with morphine 2a make the biocatalyst promising for pharmaceutical applications. [Copyright &y& Elsevier]

The diallel cross design is frequently utilized to obtain information on genetic effects, estimates of General and Specific Combining Ability (GCA and SCA) and to identify promising heterotic combinations as well as heterotic patterns. In the present study, heterotic crosses were identified for specific alkaloids in opium poppy (Papaver somniferum L.) following Yan's GGE Biplot model by use of 5×5 full diallel data. The results obtained through biplot analysis were compared with those obtained through Griffing's to check and confirm the accuracy of Yan's GGE biplot model. Parents A (papline), B (NB5KR40-7/2-3), and E (58/1) were identified as good general combiners. The crosses B×C, B×E and E×B for morphine, C×D and C×E for narcotine, and A×B, A×C and A×E were identified as heterotic combinations. None of the crosses were found heterotic for codeine and thebaine. [ABSTRACT FROM AUTHOR]

Abstract: The content of pharmaceutically important alkaloids (morphine, codeine, thebaine, papaverine and narcotine) was analysed in the empty poppy capsules (poppy straw) of fifteen selected cultivars of Papaver somniferum. By applying the cluster analysis and k-means methods, four clusters representing the sets of cultivars with a defined level of production of the selected alkaloids were determined, based on their similarities. The content of individual minor alkaloids, which was obtained was relatively low (0.00–0.17%) and in some cases negligible, defined by the dominant representation of morphine in the alkaloid spectrum of all selected cultivars. In addition to the high-morphine cultivar ‘Buddha’ (mean 1.64%), there was a middle content (mean 0.79%) or low content (mean 0.61%) of morphine in the cultivars included in clusters 2 and 3 (average of 3 consecutive years 2007, 2008 and 2009). A relatively high content of morphine was detected in cultivar ‘Böhmův bělosemenný’ (mean 0.91%), although it is usually published that white-seed cultivars contain less morphine and other alkaloids, compared to blue-seed or grey-seed cultivars. Low content of morphine (mean 0.48% resp. 0.44%) by relatively high content of narcotine (mean 0.11% resp. 0.15%) was obtained in poppy cultivars ‘Danneborg’ and ‘Tatarstan’. Also, surprisingly the highest papaverine content (mean 0.07%) was detected in the cultivar ‘Sušický červenosemenný’ with the lowest content of morphine (mean 0.34%). [Copyright &y& Elsevier]

Summary: Opium poppy (Papaver somniferum) produces medicinally important benzylisoquinoline alkaloids, including the analgesics codeine and morphine, in the morphinan pathway. We aligned three dioxygenases that were recently discovered in P. somniferum and subsequently identified the nonconserved regions. Two of these enzymes, codeine O-demethylase (PsCODM) and thebaine O-demethylase (PsT6ODM), are known to facilitate regioselective O-demethylation in morphinan biosynthesis. We systematically swapped the residues that were nonconserved between the PsCODM and PsT6ODM sequences to generate 16 mutant PsCODM proteins that could be overexpressed in Escherichia coli. While wild-type PsCODM can demethylate both codeine and thebaine, one engineered PsCODM mutant selectively demethylates codeine. Use of this reengineered enzyme in the reconstitution of morphine biosynthesis could selectively disable a redundant pathway branch and therefore impact the yields of the downstream products codeine and morphine in subsequent metabolic engineering efforts. [ABSTRACT FROM AUTHOR]

Summary Opium poppy ( Papaver somniferum) remains the sole commercial source for several pharmaceutical alkaloids including the narcotic analgesics codeine and morphine, and the semi-synthetic drugs oxycodone, buprenorphine and naltrexone. Although most of the biosynthetic genes have been identified, the post-transcriptional regulation of the morphinan alkaloid pathway has not been determined. We have used virus-induced gene silencing (VIGS) as a functional genomics tool to investigate the regulation of morphine biosynthesis via a systematic reduction in enzyme levels responsible for the final six steps in the pathway. Specific gene silencing was confirmed at the transcript level by real-time quantitative PCR (polymerase chain reaction), and at the protein level by immunoblot analysis using antibodies raised against salutaridine synthase (SalSyn), salutaridine reductase (SalR), salutaridine 7- O-acetyltransferase (SalAT), thebaine 6- O-demethylase (T6ODM), codeinone reductase (COR), and codeine O-demethylase (CODM). In some cases, silencing a specific biosynthetic gene resulted in a predictable accumulation of the substrate for the corresponding enzyme. Reduced SalSyn, SalR, T6ODM and CODM protein levels correlated with lower morphine levels and a substantial increase in the accumulation of reticuline, salutaridine, thebaine and codeine, respectively. In contrast, the silencing of genes encoding SalAT and COR resulted in the accumulation of salutaridine and reticuline, respectively, which are not the corresponding enzymatic substrates. The silencing of alkaloid biosynthetic genes using VIGS confirms the physiological function of enzymes previously characterized in vitro, provides insight into the biochemical regulation of morphine biosynthesis, and demonstrates the immense potential for metabolic engineering in opium poppy. [ABSTRACT FROM AUTHOR]

Abstract: Opium poppy (Papaver somniferum L.) is an important medicinal plant produces more than 80 alkaloids belonging to various tetrahydrobenzylisoquinoline derived classes. These alkaloids are obtained from the capsules and straw of the plant. Information on the nature and magnitude of gene effects are required for genetic improvement. Therefore, the continuous assessment of newer breeding materials is mandatory on part of breeders. The objective of this study was undertaken to understand the particular gene action involved in the inheritance of yield and component traits. Two families (VG26×VG20 and SG35II×VE01) of opium poppy were analyzed to study the gene actions involved in the inheritance of yield and component traits (plant height, leaves per plant, capsules per plant, peduncle length, capsule index, seed and straw yield per plant and morphine content). Simple additive, dominance, and epistatic genetic components were found to be significant. Dominance effect (‘h’) was higher than additive effect (‘d’) for capsule index and morphine content. Digenic interaction indicated the prevalence of dominance×dominance (‘l’) followed by additive×dominance (‘j’) type epistasis. The opposite sign of dominance (‘h’) and dominance×dominance (‘l’) indicated duplicate epistasis for all the traits. Biparental mating followed by recurrent selection involving desired recombinants may be utilized to improve the component traits. [Copyright &y& Elsevier]

The use of papaver somniferum (from the Latin fero ferre = 'to bear/bring' and somnium = 'sleep') as a narcotic, goes back to the 13th century BC. The works of ancient authors such as Dioscorides, Celsus, Galen, Theophrastus and Pliny the Elder provide us with detailed information about the morphology of the plant, its processing and the administration of the drug. These authors make it clear that opium was mainly employed as anodyne and narcotic but they also documented its use as a drug in the treatment of a variety of ailments, either as one of many ingredients in a medicinal recipe or as the main ingredient. Modern botanical and pharmaceutical analysis of the plant and its active ingredients provide us with some surprising conclusions regarding its effectiveness in the treatment of the medical conditions for which it was prescribed in the 1st and 2nd century. [ABSTRACT FROM AUTHOR]

In this sttuddy we analized dynamic of morfine content in different organs of five selected lines of Papaver somniferum L. during ontogenetic cycle. Five selected by self pollination lines (with pink, white, mauve, dark mauve and red petals) were use in our experiment. The collection of sample material and the analysis of the morphine content were conducted along five stages of vegetation corresponding to the the most important moments in the ontogenetic development of plants: rosette stage at 25 day after germination, bud initiation stage at 43 day after germination, bud dropping stage at 61 day after germination, flowering stage at 75 day after germination and lancing stage at 85 day after germination. The earlier stage of morphine detection was in rosette study only in the roots in the 0.001% d.w. The level of morphine in the leaves of all genotypes increased starting at the 43th day after germination and ending at the green capsule stage. During bud dropping stage (pendulous bud) the roots was recorded a higher morphine amount, which decreases to extinction in the lancing stage. The comparative analyze of morphine content of five different genotypes using in our experiment show that no many difference between morphine accumulation profiles during the life cycle. [ABSTRACT FROM AUTHOR]

Abstract: Five varieties (‘Minoan’, ‘Medea’, ‘Korona’, ‘Przemko’, ‘Kozmosz’) of poppy representing different chemotypes were combined and the alkaloid profiles of F1–F3 progenies were studied during 2006–2009. In the crosses of high alkaloid containing varieties the content of total alkaloids and that of morphine and thebaine showed increased levels in the hybrid generations which persisted till F3. Narcotine (noscapine), however accumulated at lower level than the midparent values and showed a decreasing tendency over generations. A higher number of homogenous strains starts to appear in F3 progenies. The majority of codeine containing individuals concentrates to certain strains. A growing number of high thebaine containing individuals was observed in several combinations. In the crosses with low alkaloid containing parent (‘Przemko’) the F1 exhibits considerable heterosis for total alkaloid content. Low alkaloid containing recessive individuals segregate in F2 and stabilise in F3. Results of our crossing experiments reflected well the effects of genetic regulation at three levels of enzymatic processes during the biosynthesis of poppy alkaloids. Data support the recessive determination of transformations at TyDC (tyrosine decarboxylase) and BBE (berberine bridge enzyme) levels while more complex (polygenic) effects are supposed in controlling the quantity of narcotine (noscapine) and morphinanes. Selection for fixing very low alkaloid content and narcotine may be effective in early F2 generations, however a selection for morphinanes is not worthy before F3. [Copyright &y& Elsevier]

When and how the potency of the sap of the opium poppy was discovered by man is shrouded in mystery. It has been suggested that humans were attracted to the poppy plant because of its colorful flowers. Historically, there have been two basic ways to indulge in opium-taking: one was to eat it, and the other to smoke it. For a period of about 200 years, opium was instrumental in affecting a very high proportion of lives of peoples in Europe, Asia, and perhaps even in the New World. Fortunes were made and lost by merchants trading in opium. Wars were fought over it and the results affected entire empires. Several famous writers, poets, and musicians were among its users during the 19th century. It is difficult to say if opium affected the quality of their output. Migrations of Indian indentured labor for harvesting sugarcane in the far corners of the British Empire during the late 1800s and early 1900s was also a result of colonial policy of opium growing and export. The cultivation, land preparation of the opium poppy, and refining of its exude into a more potent heroin are discussed. However, the detrimental effects of opium-taking became clear in the 20th century and its narcotic use is banned in almost all countries of the world today. But despite everything opium did provide great relief as a painkiller in both world wars when converted into morphine. Just as atomic energy is a boon to mankind, the atomic bomb destroys. Almost every opium user exhorts the virtues of the narcotic at the beginning but invariably regrets the habit later on when it eventually leads to a painful death. [ABSTRACT FROM AUTHOR]