Alkaloid Accumulation and Distribution within the Capsules of Two Opium Poppy (Papaver somniferum L.) Varieties.

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.

The effects of opium consumption on severity of disease on hospitalized COVID-19 patients in East of Iran, a prospective cohort study.

There are few theories and little empirical evidence about the bilateral impact of substance use and coronavirus disease 2019 (COVID-19), so a logical and accurate picture of this area is required. We investigated the effects of opium use on severity of disease on hospitalized COVID-19 patients in east of Iran. Demographic and clinical characteristics, vital signs, laboratory tests, mortality rate, type and duration of opium consumption in hospitalized patients who recovered from COVID-19 in the follow-up after 3 months were evaluated. In this study, 60 (20%) participants were the opium user and 251 (80%) were the non-user patients. Based on clinical symptoms, hypertension and systolic blood pressure in opium user were significantly higher than non-user patients (p < 0.05). In the laboratory tests, only the level of urea was higher in the opium positive group (37 [26.5-48.5] vs. 32 [23-43], respectively) and the percent of lymphocytes were lower in the opium positive (17 [8.2-25.8] vs. 18.7 [13.85-26.35], respectively). The initial therapies of both opium positive and negative infected patients showed not any significant changes (p > 0.05). Among the studied groups, one deceased case with COVID-19 was related to a drug user patient. Although, uses of opium reduced the levels of some risk factors, vital signs at admission and initial therapies during hospitalization in COVID-19 patients but it increased lung and heart diseases. Also, the severity of COVID-19 including hospitalization and mortality were associated with opium consumption.

Comparison of direct analysis in real-time mass spectrometry, atmospheric solids analysis probe-mass spectrometry, and ion mobility spectrometry for ensuring food safety by rapid screening of poppy seeds.

The opium poppy (Papaver somniferum) is a global commercial crop that has been historically valued for both medicinal and culinary purposes. Naturally occurring opium alkaloids including morphine, codeine, thebaine, noscapine, and papaverine are found primarily in the latex produced by the plant. If the plant is allowed to fully mature, poppy seeds that do not contain the opium alkaloids will form within the pods and may be used in the food industry. It is possible for the seeds to become contaminated with alkaloids by the latex during harvesting, posing a potential health risk for consumers. In the USA, there have been more than 600 reported adverse events including 19 fatalities that may be linked to the consumption of a contaminated poppy-containing product such as home-brewed poppy seed tea. Unwashed poppy seeds and pods may be purchased over the Internet and shipped worldwide. The Forensic Chemistry Center, US Food and Drug Administration (FDA) has evaluated several mass spectrometers (MS) capable of rapid screening to be used for high-throughput analysis of samples such as poppy seeds. These include a direct analysis in real-time (DART) ambient ionization source coupled to a single-quadrupole MS, an atmospheric solids analysis probe (ASAP) ionization source coupled to the same MS, and ion mobility spectrometers (IMS). These instruments have been used to analyze 17 poppy seed samples for the presence of alkaloids, and the results were compared to data obtained using liquid chromatography with mass spectral detection (LC-MS/MS). Results from the 17 poppy seed samples indicate that the DART-MS, ASAP-MS, and IMS devices detect many of the same alkaloids confirmed during the LC-MS/MS analyses, although both the false-positive and false-negative rates are higher, possibly due to the non-homogeneity of the samples and the lack of chromatographic separation.

Studies on Sensory and Phytochemical Characteristics of Poppy (Papaver somniferum L.) Varieties for Their Oil Utilisation.

Poppy is a significant pharmaceutical crop, but the seeds and the cold-pressed oil have a big potential as healthy foods. Breeding has mainly focused on agronomical characteristics and alkaloid content. Here, we compared the sensory values, fatty acid and headspace volatile composition of poppy oils and flours produced from different varieties. Two industrial and four culinary varieties were cultivated in our field in 2021-2022. The sensory test differentiated well among varieties. Typical poppy odour and flavour were stronger both in the oils and the flours of the blue-seed varieties compared to the white-seed ones. For most varieties, the harvest year caused no relevant differences. Linoleic, oleic, and palmitic acids were the main components both in oils and flours. Larger differences were detected in the volatiles (e.g., 2 and 3 methyl-butanal and 3 methyl-butanol γ-n-caprolactone, pentofuran), depending on genotype and year. A higher ratio of saturated fatty acids negatively influenced the flavour and odour characteristics. In the headspace volatiles, these features correlated negatively with 2-pentylfuran and hexanal. The oil content of poppy flour has a positive effect on colour, appearance, tactility and poppy flavour. Our results support a goal-oriented use of poppy genotypes for high-quality dietary products.

Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application.

The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of Papaver somniferum L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterase in smooth muscles, and it has been observed to increase intracellular levels of cAMP and cGMP. It induces coronary, cerebral, and pulmonary artery dilatation and helps to lower cerebral vascular resistance and enhance cerebral blood flow. Current pharmacological research has revealed that papaverine demonstrates a variety of biological activities, including activity against erectile dysfunction, postoperative vasospasms, and pulmonary vasoconstriction, as well as antiviral, cardioprotective, anti-inflammatory, anticancer, neuroprotective, and gestational actions. It was recently demonstrated that papaverine has the potential to control SARS-CoV-2 by preventing its cytopathic effect. These experiments were carried out both in vitro and in vivo and require an extensive understanding of the mechanisms of action. With its multiple mechanisms, papaverine can be considered as a natural compound that is used to develop therapeutic drugs. To validate its applications, additional research is required into its precise therapeutic mechanisms as well as its acute and chronic toxicities. Therefore, the goal of this review is to discuss the major studies and reported clinical studies looking into the pharmacological effects of papaverine and the mechanisms of action underneath these effects. Additionally, it is recommended to conduct further research via significant pharmacodynamic and pharmacokinetic studies.

Papaver somniferum and Papaver rhoeas Classification Based on Visible Capsule Images Using a Modified MobileNetV3-Small Network with Transfer Learning.

Traditional identification methods for Papaver somniferum and Papaver rhoeas (PSPR) consume much time and labor, require strict experimental conditions, and usually cause damage to the plant. This work presents a novel method for fast, accurate, and nondestructive identification of PSPR. First, to fill the gap in the PSPR dataset, we construct a PSPR visible capsule image dataset. Second, we propose a modified MobileNetV3-Small network with transfer learning, and we solve the problem of low classification accuracy and slow model convergence due to the small number of PSPR capsule image samples. Experimental results demonstrate that the modified MobileNetV3-Small is effective for fast, accurate, and nondestructive PSPR classification.

Structural Characterization and Molecular Dynamics Study of the REPI Fusion Protein from Papaver somniferum L.

REPI is a pivotal point enzyme in plant benzylisoquinoline alkaloid metabolism as it promotes the evolution of the biosynthetic branch of morphinan alkaloids. Experimental studies of its activity led to the identification of two modules (DRS and DRR) that catalyze two sequential steps of the epimerization of (S)- to (R)-reticuline. Recently, special attention has been paid to its genetic characterization and evolutionary history, but no structural analyses of the REPI protein have been conducted to date. We present here a computational structural characterization of REPI with heme and NADP cofactors in the apo state and in three complexes with substrate (S)-reticuline in DRS and intermediate 1,2-dehydroreticuline in DRS and in DRR. Since no experimental structure exists for REPI, we used its AlphaFold model as a scaffold to build up these four systems, which were submitted to all-atom molecular dynamics (MD) simulations. A comparison of MD results for the four systems revealed key dynamic changes associated with cofactor and ligand binding and provided a dynamic picture of the evolution of their structures and interactions. We also explored the possible dynamic occurrence of tunnels and electrostatic highways potentially involved in alternative mechanisms for channeling the intermediate from DRS to DRR.

Nutritional and Chemical Characterization of Poppy Seeds, Cold-Pressed Oil, and Cake: Poppy Cake as a High-Fibre and High-Protein Ingredient for Novel Food Production.

Currently, society demands natural healthy foods with improved nutritional characteristics. Accordingly, poppies (Papaver somniferum) are a traditional crop, cultivated for food and pharmaceutical purposes, whose seeds meet consumers' preferences, making them a promising candidate for incorporation into the formulation of novel functional foods. This work performed an overall chemical characterization of poppy seeds, cold-pressed oil, and press cake, a by-product of the oil industry. The proximate composition, fatty acids, and vitamin E profiles of the oil fraction were analysed with respect to the whole seeds and the cake. The cold-press oil extracted from the poppy seeds was also characterized. Since poppy cake is a partially defatted product, it has a lower fat content than the seeds, but higher content of the rest of its elements, namely, ash (10%), protein (26%), and fibre (38%). Regarding protein composition, the major amino acid in the cake and seeds was determined to be glutamic acid (59 and 36 mg/g, respectively). All the samples presented α- and γ-tocopherols (>21 and >25 mg/kg, respectively) and the fatty acids profile of the oil fraction was mainly composed of unsaturated fatty acids, where linoleic acid predominates (>50%). The oil's oxidative stability was low (2.8 h), according to the predominance of unsaturated fatty acids. Thus, poppy cake may be considered as an ingredient with great potential for incorporation into products in the food industry according to its high content in protein and fibre, and the remaining fat content, where polyunsaturated fatty acids predominate.

Opium abuse and stroke in Iran: A systematic review and meta-analysis.

Introduction: Opium dependence is a significant health concern in low and middle-income countries, leading to a considerable number of deaths annually. Opium has several detrimental effects on its consumers. Data regarding the impact of opium on stroke are controversial. The objective of this study is to evaluate the association between opium dependence and stroke. Methods: I conducted a systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the association between opium dependence and stroke. Following the extraction of qualitative findings from included studies, a meta-analysis was performed to assess the pooled estimate of odds ratios (ORs). Results: Eight and four studies were included in qualitative and quantitative synthesis, respectively. Opium dependence increases the hazard of stroke mortality. Also, opium increases the odds of ischemic stroke by 127% (pooled OR = 2.27, 95% CI: 1.47-3.07). Conclusion: Opium not only merely increases the odds of being diagnosed with ischemic stroke but also leads to a notable increase in the mortality rate following stroke.

Emerging trends in genomic and epigenomic regulation of plant specialised metabolism.

Regulation of specialised metabolism genes is multilayered and complex, influenced by an array of genomic, epigenetic and epigenomic mechanisms. Here, we review the most recent knowledge in this field, drawing from discoveries in several plant species. Our aim is to improve understanding of how plant genome structure and function influence specialised metabolism. We also highlight key areas for future exploration. Gene regulatory mechanisms influencing specialised metabolism include gene duplication and neo-functionalization, conservation of operon-like clusters of specialised metabolism genes, local chromatin modifications, and the organisation of higher order chromatin structures within the nucleus. Genomic and epigenomic research to-date in the discipline have focused on a relatively small number of plant species, primarily at whole organ or tissue level. This is largely due to the technical demands of the experimental methods needed. However, a high degree of cell-type specificity of function exists in specialised metabolism, driven by similarly specific gene regulation. In this review we focus on the genomic characteristics of genes that are found in different types of clusters within the genome. We propose that acquisition of cell-resolution epigenomic datasets in emerging models, such as the glandular trichomes of Cannabis sativa, will yield important advances. Data such as chromatin accessibility and histone modification profiles can pinpoint which regulatory sequences are active in individual cell types and at specific times in development. These could provide fundamental biological insight as well as novel targets for genetic engineering and crop improvement.

Evaluation of chloroplast DNA barcoding markers to individualize Papaver somniferum for forensic intelligence purposes.

The opium poppy, Papaver somniferum L., is a forensically important plant due to the medicinal and illegal uses for the milky latex stored in the pods. This latex contains the alkaloids morphine, codeine, and thebaine that are used for their analgesic properties and/or for synthesizing other opioids. However, these compounds are highly addictive and have caused a national opioid epidemic. Two other Papaver species, P. setigerum DC. and P. bracteatum Lindl., are also of forensic interest because they pose both forensic and legal issues. They are largely uncontrolled under the Controlled Substances Act, making these species a common defense strategy. Current morphological and chemical identification methods have been moderately successful but have drawbacks. There is also a lack of sequencing data available. Therefore, exploiting the genome using chloroplast DNA barcoding markers could help to accurately identify these species of interest when plant material is taken. This study screened and assessed the genetic variation both between species and within populations of P. somniferum in nine cpDNA barcode regions (ndhF-rpl32, petA-psbJ, rpl32-trnL, rps16-trnQ, trnE-trnT, trnH-psbA, trnL-trnF, rpl16 intron, and psbE-petL). Published reference genomes from the NCBI GenBank database were aligned and compared for an initial in silico screening. Additionally, ten P. somniferum seed samples from various vendors were sequenced and compared across samples and to published reference data at the various barcode regions of interest. This study showed that the regions trnH-psbA and petA-psbJ have promise for utility in individualization for both inter- and intra-species individualization of P. somniferum.

Opium, Street Opium, and Cancer Risk.

Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics; designing less addictive opioids is an active area of pharmaceutical research that may lead to significant improvements in chronic pain management. Recently, the International Agency for Research on Cancer (IARC) has classified opium consumption as carcinogenic to humans (Group 1) based on sufficient evidence of carcinogenicity in human studies. However, all human studies analyzed by the IARC Working Group included participants who consumed opium that was mixed, adulterated, and/or contaminated with known and probable human carcinogens (e.g., tarry residues of combusted opium, arsenic, lead, and chromium). The working group considered that these carcinogens were part of the complex mixture that opium is, rather than co-exposure or confounders. No evidence of carcinogenicity was available for pure opium in human, animal, or mechanistic studies. To avoid confusion and concern among health professionals and patients using medicinal opium preparations and in scientists involved in the design and development of new opium derivatives, opium should be classified in Group 3 (not classifiable as to its carcinogenicity to humans). The term 'street opium' could be used to refer to opium that probably contains human carcinogens not present in pure opium and should remain in Group 1 (carcinogenic to humans).

Kamini, a little recognised source of illicit opioid: A case series of 12 patients.

INTRODUCTION: This case series describes 12 patients who developed opioid use disorder after ingesting a prohibited, imported herbal product, Kamini, which contains Papaver somniferum. They appeared unaware of the risk of dependence from Kamini and most had struggled to manage their use for many months before presenting for treatment. METHODS: After two cases were presented at a clinical meeting, a chart review was conducted of cases across four public opioid treatment clinics in south-east Queensland with about 1500 patients registered, identifying 10 further cases. RESULTS: Twelve patients presented with features of opioid withdrawal, seeking treatment after use of Kamini for periods between 6 months and 8 years. Eleven patients were born in India. Nine patients stabilised on buprenorphine maintenance treatment, three of whom commenced long-acting injectable buprenorphine. One patient left after 1 day and subsequently began methadone treatment with a private prescriber. Two patients on smaller doses and shorter-term use undertook withdrawal with prescribed (off-label) trans-dermal buprenorphine. One patient, initially lost to follow-up, later stabilised on long-acting injectable buprenorphine. Reasons for presenting included supply shortages and financial distress during the COVID-19 pandemic. DISCUSSION AND CONCLUSION: Kamini represents an illicit source of non-prescription opioid in Australia. Although classified as an illegal import by the Therapeutic Goods Administration, patients confirm that it is readily available in Brisbane. Targeted efforts are needed to prevent further patients developing opioid dependence from use of Kamini and also to highlight treatment options for those seeking to stop Kamini use.

Assessment of Dry Heating, Water Rinsing, and Baking on Concentrations of the Opium Alkaloid Noscapine in Poppy Seeds.

Limited information is available on methods to reduce concentrations of the opium alkaloid noscapine in poppy seeds. A series of experiment were conducted using poppy seeds to evaluate the impact of thermal treatments, water rinsing, and baking on noscapine concentrations. A sample set of commercially available poppy seeds (n=15) was screened for noscapine using liquid chromatography-tandem mass spectrometry. The mean and median noscapine concentrations for poppy seed samples above the limit of quantitation (LOQ) was 89.9 and 28.4 mg kg-1, respectively. Six out of 15 samples were less than the LOQ. Poppy seed samples containing a mean noscapine concentration of 121 mg kg-1 were subjected to dry heat treatments ranging from 120-200 °C and a 5 min rinse with water. Baking experiments were also done by incorporating the poppy seeds into a muffin batter and baking in an oven at 200 °C. The dry heat treatment experiments showed that noscapine degraded at 160-200 °C, with a 50% loss of noscapine observed after 3.44 ± 0.46 min at 200 °C. Although the mean concentration of noscapine decreased when a muffin containing poppy seeds was baked at 200 °C for 16 min, these changes were not statistically significant (P>0.05). Rinsing the poppy seeds with water did not have a significant effect on noscapine concentrations. Together, these data allow for better characterization of potential dietary exposure to noscapine and indicate that certain thermal treatments can be effective for reduction of noscapine in poppy seeds.

Forensic Application of Genetic and Toxicological Analyses for the Identification and Characterization of the Opium Poppy (Papaver somniferum L.).

BACKGROUND: A reliable and science-based taxonomic determination of Papaver somniferum L. (opium poppy), the illegal species of the genus Papaver, may have practical and legal implications for law enforcement. P. somniferum is a controlled plant because of its narcotic substances, such as morphine and codeine. As poppy plants have rather similar morphological features, both chemical and genetic analysis are required in order to achieve an accurate characterization of such species. The chemical structures of alkaloids are extremely variable even within the same species, which is why the genetic approach may lead to a more scientific Papaver sp. differentiation. The aim of our study was the taxonomic identification of poppy capsules seized by the Italian Police Forces being considered as potential P. somniferum derivatives. METHODS: The alkaloids detected using gas chromatography/mass-spectrometry (GC/MS) were morphine, codeine, thebaine, noscapine, meconin, hydrocotarnine, and traces of papaverine. Further genetic analysis was carried out simultaneously using three plastid DNA barcoding regions (matK, trnH-psbA, and rbcL) for the samples' identification. RESULTS: The Random Amplification of Polymorphic DNA (RAPD) method showed that the analysed samples were genetically identical. CONCLUSIONS: The morphological, toxicological, and genetic profile of the samples revealed that they belonged to P. somniferum species. Furthermore, the alkaloid content of dried poppy capsules might be used to investigate and track their origin.

Development of SSR and SNP markers for identifying opium poppy.

Papaver somniferum L. (opium poppy) is the original plant of heroin, which is a major narcotic drug, and this plant has brought great harm to human health. However, the ban on opium poppy cultivation and trafficking is facing great challenges because of abnormal profits. Therefore, rapid and accurate identification is important to address the abovementioned problems. In this study, eleven simple sequence repeats (SSR) markers and two single nucleotide polymorphism (SNP) markers were mined to distinguish opium poppy from other six Papaver species. These molecular markers were further verified through a large number of plant materials of these seven Papaver species. An excellent multiplex polymerase chain reaction (PCR) system that simultaneously amplifies the three of eleven SSR markers was developed, which effectively improves the efficiency and speed of identification. The present research is of great implication for identifying and investigating the illegal cultivation and trafficking of opium poppy.

Interindividual variability in diabetic patients' response to opium poppy: an overview of impressive factors.

Diabetic patients always seek alternative treatments to lower their blood glucose level efficiently, because antidiabetic drugs produce adverse effects and many patients experience reduced response after a treatment period. Opium poppy (Papaver somniferum) is frequently consumed by diabetic patients for reduction of blood glucose level. Scientific studies found controversial results in the investigation of the blood glucose-lowering effects of opium poppy. In this regard, we explored the antidiabetic effect of opium poppy more closely. The antidiabetic or antihyperglycemic effect of P. somniferum alkaloids were reviewed. Next, opioid receptors and their role in diabetes were explored. In the final part origins of interindividual variabilities in opioid receptors and metabolizing enzymes' functions including genetic and epigenetic factors were reviewed.

Molecular identification and phylogenetic analysis of Papaver based on ITS2 barcoding.

In forensic cases suspected to involve Papaver somniferum, species identification is key to the investigation. To accurately detect and identify P. somniferum as well as common adulterants of the same genus, 19 internal transcribed spacer 2 (ITS2) sequences of P. somniferum (256 bp), Papaver canescens (254 bp), Papaver nudicaule (254 bp), Papaver pavoninum (250 bp), Papaver radicatum (254 bp), and Papaver rhoeas (256 bp) were obtained. Based on the ITS2 sequence, similarity analysis via BLAST, the nearest Kimura-2-parameter (K2P) genetic distances were calculated, and a phylogenetic tree was constructed using MEGA X software for the identification of six species of Papaver. Finally, differences in the ITS2 secondary structure between species were analyzed. The best matches of the P. somniferum ITS2 sequence were of other P. somniferum from different sources. The nearest K2P genetic distances between P. somniferum and its counterparts from other sources were zero, which was the smallest pairwise genetic distance among distances from the other five Papaver species. Various sources of P. somniferum clustered into an independent branch in the phylogenetic tree. The secondary structures of P. somniferum and P. rhoeas were significantly different from those of the other four species of Papaver. In summary, P. somniferum can be effectively distinguished from five closely related plants of the same genus by using ITS2 as a DNA barcode.