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Opium Poppy ( Papaver somniferum), POPPY LATEX, opioid receptors, GI…
Opium Poppy ( Papaver somniferum)
Regulation of the alkaloid biosynthesis by miRNA in opium poppy
Opium poppy (Papaver somniferum) is an agronomically and economically important medicinal plant used for main morphinan alkaloid production (Ziegler and Facchini, 2008). The opium poppy synthesizes large amount of benzylisoquinoline alkaloids (BIA) as secondary metabolites. The latex of the poppy capsule mainly includes morphine and relatively low levels of other BIA alkaloids, such as codeine, papaverine, thebaine and noscapine (Page, 2005).
Boke, H., Ozhuner, E., Turktas, M., Parmaksiz, I., Ozcan, S., & Unver, T. (2015, March 04). Regulation of the alkaloid biosynthesis By miRNA in opium poppy. Retrieved February 12, 2021, from
https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.12346
Short- and Long-term Opioid Use in Patients with Oral and Oropharynx Cancer
McDermott, Jessica D, et al. “Short- and Long-Term Opioid Use in Patients with Oral and Oropharynx Cancer.” Otolaryngology--Head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery, U.S. National Library of Medicine, 6 Nov. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6886698/.
Opioid use and abuse is a national health care crisis, yet opioids remain the cornerstone of pain management in cancer. We sought to determine the risk of acute and chronic opioid use with head and neck squamous cell cancer (HNSCC) treatment.
Oxycodone prescribed as the first opioid was the least likely to lead to ongoing use at 3 and 6 months
The Centers for Disease Control and Prevention (CDC) estimates that opioid addiction and overdose claimed more than 70,000 lives in 2017 and has resulted in an estimated annual economic cost of $78.5 billion
Long-term use was consistently associated with tobacco use, prior opioid use, and type of opioid use.
This latter study had a very high percentage of patients who screened positive for alcoholism (30%), which was found to be a significant predictor for chronic opioid use and may have contributed to their high ongoing use.
Use of long-acting opioid medications was a risk factor for ongoing use at 3 months while high daily doses of opioids (>100 mg morphine equivalent) were a risk factor for persistent use at 6 months
Opioid use has been associated with worse physical symptoms (constipation, insomnia, lack of energy, anorexia, etc) and lower quality of life measures in cancer and noncancer patients.
Nonopioid alternative agents and treatments including acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentin, tricyclic antidepressants, physical therapy, and acupuncture have been evaluated in small series to manage HNSCC treatment-related toxicity with mixed effects.
Further research and use of these and other opioid-sparing medications and treatments will be critical to reduce acute and chronic opioid use in patients with curative HNSCC.
CONCLUSIONS
Persistent use at 3 and 6 months remains high relative to the general population with patient and opioid prescribing patterns as significant risk factors. These findings underline the importance of monitoring high-risk patients, evaluating the types of opioid medications prescribed, and finding alternative pain management regimens that can decrease short- and long-term opioid use.
The Economic Burden of Prescription Opioid Overdose, Abuse and Dependence in the United States, 2013
The total economic burden is estimated to be $78.5 billion. Over one third of this amount (is due to increased health care and substance abuse treatment costs ($28.9 billion)
Approximately one quarter of the cost is borne by the public sector in health care, substance abuse treatment, and criminal justice costs.
Prescription opioids account for approximately 70% of fatal prescription drug overdoses.
From 2007 to 2013, the annual number of prescription opioid overdose deaths has increased by over 1,800 cases
In 2013, an estimated 1.9 million people reported prescription opioid abuse or dependence, while 517,000 reported heroin abuse or dependence (with some reporting both).
In the ideal case, decision makers could use these estimates when weighing the benefits and risks of using opioids to treat pain, and evaluating prevention measures to reduce harmful use.
Florence, Curtis S, et al. “The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013.” Medical Care, U.S. National Library of Medicine, 30 May 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5975355/.
ON OPIUM: ITS HISTORY, LEGACY AND CULTURAL BENEFITS
Thomas Sydenham, the celebrated “father of English medicine,” once said: “Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium”
Opium, or poppy tears, is the dried latex derived from opium poppies.
piates, defined in medicine, refer to the alkaloids naturally found in opium poppies, and opioids are the synthetic drugs that resemble opiates.
Opium’s influence throughout history stretches well beyond China’s widely noted opium wars in the 19th century, as Carbon-14 dating records it use as early as 4200 B.C.
The earliest findings of opium poppy cultivation come from Mesopotamia in 3400 B.C. There, Sumerians named the plant Hul Gil, or “joy plant” (Brownstein 1993).
in Egyptian mythology, Thoth holds credit for the creation of opium, while Isis allegedly used the plant on Ra to treat a headache. Egypt limited opium’s use to magicians, priests, and warriors. In Greek mythology, the gods Hypnos, Nyx, and Thanatos (deities of sleep, night, and death, respectively) often held or wore a wreath of poppies.
In 1874, after experimenting with morphine, British scientist C. R. Alder Wright synthesized the earliest opiate called diacetylmorphine, now known more commonly as heroin.
In 1900, the Eli Lilly pharmaceutical company began selling heroin over the counter in the United States and marketed the drug as a treatment for cough and flu alongside Aspirin. In World War I, doctors administered heroin intravenously to fatally wounded and anguished soldiers on a normal basis. By the 1920s, heroin’s risks outweighed its advantages, and clinicians pushed for the drug’s recall.
Today, heroin prescriptions are still available in some countries like Great Britain, where they remarket the product as diamorphine and use it as an analgesic.
Flascha, Carlo. “ON OPIUM: ITS HISTORY, LEGACY AND CULTURAL BENEFITS.” PROSPECT, UCSD International House, 25 May 2011, prospectjournal.org/2011/05/page/2/.
A brief history of opiates, opioid peptides, and opioid receptors.
Brownstein, Michael J. “A Brief History of Opiates, Opioid Peptides, and Opioid Receptors.” NCBI, PubMed Central, 15 June 1993, www.ncbi.nlm.nih.gov/pmc/articles/PMC46725/.
In 1898, heroine was synthesized and Pronounced to be more potent than morphine and free from abuse liability. This was the first of several such claims for novel opiates. To date, none has proven valid
The opioid receptors are all acknowledged to be guanine nucleotide binding (G)-protein-coupled.
Both µ and ∂ receptors mediate the inhibition of adenylate cyclase and the activation of inwardly rectifying potassium channels
K and ∂ receptors have also been shown to inhibit the opening of voltage-dependent calcium channels.
Opium and Its Alkaloids
Schiff Jr, Paul L. “Opium and Its Alkaloids .” Archive, American Journal of Pharmaceutical Education, 3 Nov. 2002, archive.ajpe.org/legacy/pdfs/aj660217.pdf.
The opium poppy, Papaver somniferum L. (Papaveraceae), is one of the oldest medicinal plants in recorded history. It is believed that the plant originated in Asia Minor, but the exact time and place of discovery are unknown.
the first mention of the opium poppy is found on Sumerian clay tablets inscribed in Cuneiform script in about 3000 BC. These tablets were found at Nippur, a spiritual center of the Sumerians located south of Baghdad, and described the cultivation of the opium poppy, including the collection of poppy juice in the early morning, with the subsequent production of opium.
The Assyrians, like the Sumerians, also collected poppy juice early in the morning (via scraping the poppy capsule with an iron scoop) and placed these collections in earthen pots.
The ancient Egyptians cultivated opium poppies, however the use of opium was generally restricted to priests, magicians, and warriors, and was associated with religious cultism
The word “opium” has been postulated to be of Greek origin, deriving from “opos” (juice) and “opion” (poppy juice).
The League of Nations subsequently assumed this role, and all signatory countries agreed to pass laws and regulations to limit the import, sale, distribution, export and use of all narcotic drugs to medical and scientific purposes.
WHAT IS THE STRUCTURE?
The opium poppy is an annual herb with an erect stem, having a solitary flower that is white, red, or purplish, depending on the cultivar. All parts of the plant exude a white latex on incision.
characterized by white flowers and seeds is commonly cultivated in India, and is traditionally designated as the variety album.
CHEMISTRY
followed by simple chemical transformations of the alkaloid, such as its acetylation to heroin (diacetylmorphine) by Wright in 1874 and its methylation to codeine (monomethylmorphine) by Grimaux in 1881.
dation of dihydrocodeinone (18). Morphine (pKb 5.8) is an amphoteric pentacyclic alkaloid that exists naturally in its levorotatory form as columnar colorless prisms
The initial elemental analysis of C34H36O6N2 proposed by Liebig in 1831 was corrected to C17H19O3N by Laurent in 1847.
PHARMACOLOGY
Morphine is a classical exogenous opioid (xenobiotic opioid) that produces a well-characterized analgesia
Endogenous opioids are peptides that are the naturally occurring ligands for opioid receptors, with the term endorphin (endogenous + morphine) being coined to refer to the endogenous opioids as a group,
existence of three major types of opioid receptors [mu (µ), delta (δ), and kappa (κ)]
These receptors are members of the superfamily of G-protein-coupled receptors.
Opioid receptors are found in nerve cells located in the various regions of the brain and the spinal medulla, as well as in intramural nerve plexuses that are involved in the regulation of gastrointestinal and urogenital motility.
The mode of action of opioids involves an increase in K+ conductance (opening of IC channels) with most neurons responding via hyperpolarization. This results in a decrease of Ca++ influx into nerve termini (closing of voltage-gated Ca++ channels) and subsequent inhibition in the release of excitatory neurotransmitters and in synaptic activity. The resulting synaptic inhibition is characterized by either a depressant or an excitant effect, depending on the population of cells involved(23).
Major features of morphine and morphine-like narcotic agonists in the central nervous system include: analgesia, drowsiness, euphoria, a sense of detachment, respiratory depression (reduced sensitivity of medullary chemoreceptors to carbon dioxide), nausea and vomiting (direct stimulation of medullary emetic chemoreceptors in the area postrema), depressed cough reflex (partially via direct action on the medullary cough center), and hypothermia.
A stimulant action on the parasympathetic portion of the oculomotor nucleus (third cranial nerve) is responsible for pupillary miosis.
PRODUCTION
Cultivation of the opium poppy for the production of opium principally occurs in northern India in the regions of Madhya Pradesh, Uttar Pradesh, and Rajasthan
requires rich moist soil, plentiful sunlight, and a clear area in which to grow.
After the plants have emerged in the spring and reached a height of about 15 cm, the fields are thinned such that the remaining plants stand about 60 cm apart.
Flowering occurs in April or May, with the capsules maturing in May or June. Five to eight capsules are normally present on each plant, and as the capsules ripen to about four cm in diameter, their color changes from bluish-green to yellow.
There are four-to-six such incisions and each incision is made sufficiently deep in order to incise the lactiferous ducts, but not so deep as to penetrate the endocarp, which would result in the latex flowing inward toward the center of the capsule.
A white latex exudes from the incisions, rapidly darkening to a brownish or blackish color on exposure to air.
The morning following incision, the darkened solidified latex is collected via scraping with an iron scoop/trowel or knife prior to the heat of the day causing the latex to become sticky.
material is kneaded together into balls, wrapped in poppy leaves, and air-dried in the shade.
. Alternatively, the coagulated latex may be stored in metal or earthen pots with perforated bottoms, allowing drainage of a dark-colored fluid. If the bottoms are not perforated, the pots are stored at a tilt and turned over every ten days for drainage.
Further processing then occurs at government collection stations where the crude opium is placed in rectangular pans and allowed to sit in the sun for about 1-3 weeks.
SEED AND STRAW USE
the leaves are dry and the seeds contain a maximum of poppy seed oil (an unsaturated fixed oil).
poppy seed cake is crushed and used as a source of cattle feed.
Poppy seed oil has been as a culinary salad oil, cooking oil, drying oil for use in art, and as a vehicle for various parenteral formulations
Whole or crushed dark poppy seeds, sometimes called maw seeds, are used in various baked goods in both Europe and the United States
once thought to contain little if any alkaloids
it was determined that morphine and codeine may be detected in the urine more than 48 hours after the ingestion of culinary poppy seeds
consumption of a single poppy seed bagel could lead to the ingestion of up to 0.1 mg of codeine and up to 1.5 mg of morphine, demonstrating that a positive detection and identification of urinary morphine or codeine may not always be due to drug ingestion
The upper stalk of the plant (including the crushed capsules) may be cut and dried and the resultant poppy “straw” processed via extraction to remove the alkaloid morphine
Poppy straw is principally produced in Australia, France, Spain, Ukraine, Yugoslavia, and Turkey.
Illicit opium trade is more commonly found in remote border areas of “the Golden Triangle” (Laos, Thailand, and Myanmar), “the Golden Crescent” (Afghanistan, Iran, Pakistan), India, Lebanon, and Mexico
Presently, the cultivation of the opium poppy is internationally regulated by the International Narcotics Control Board of the United Nations, with India being the only country that is significantly involved in opium production to meet world demands.
Our Own Opium: Cultivation of the Opium
Poppy in Britain, 1740, 1823
Young, Cowley and Staines, and the Rev. G. Swayne, the latter writing in the "Quarterly Journal" were particularly interested in this aspect, producing detailed drawings and diagrams ol their inventions.
Young, he employed two convex edged scalpels, the blades of which were almost totally covered with sealing wax with only the very edge, left bare, so as to prevent the knife from penetrating the cavity of the capsules.
The scalpel blades were held 1/2'' apart and were fastened together with thread
Young was unusual in making a double incision, both longitudinally and obliquely, but he claimed more opium was obtained this way.
He used a small painter's hair brush, a sashtool, to scrape the opium off into a hip flask fastened to the breast of the gatherer.
The juice was afterwards evaporated in shallow earthen dishes.
eslimated the yield per aere at 56 Ib
Berridge, Virginia. “Our Own Opium: Cultivation of the Opium Poppy in Britain, 1740-1823.” British Journal of Addiction (to Alcohol & Other Drugs), vol. 72, no. 1, Mar. 1977, pp. 90–94. EBSCOhost, doi:10.1111/j.1360-0443.1977.tb03970.x.
Water stress effects on growth, development and yield of opium poppy (Papaver
somniferum L.)
Poppy (Papaver somniferum L.), is a plant of the dicot family
Papaveraceae, cultivated for seed, oil and opium.
It is an erect, annual herb, 30–170 cm tall; flower buds are ovate, dropping before anthesis (hook stage); the fruit is a capsule that usually contains a high number of very small seeds
In Europe, poppy seeds – that are free of alkaloids – have culinary uses in confectionery and bakery and are widely used in perfume, cosmetic and medicinal industries.
Poppy is also cultivated for opium production, the dried plant latex located mainly in the capsule walls. Opium is one of the oldest known painkillers, and the source of several alkaloids used for analgesic, antitussive and antispasmodic purposes in modern medicine (Peter, 2001).
Opium poppy is one of the most important crops for the pharmaceutical industry for the production of natural opiate alkaloids, mainly morphine, codeine and thebaine, that are extracted mainly from the crushed dried capsules emptied of seeds.
Some cultivars contain up to 50% oil in seed, mainly in the form of oleic and linoleic acids and may be used as a source of linoleic acid. The oil is of high quality for human consumption because of its high amount of polyunsaturated fatty acids
Development Stages
1.) growth of seedlings
2.) formation of rosette-type leaves and stalks
3.) budding (hook stage)
4.) flowering
technical maturity (readiness for cutting).
6.) biological maturity (ripening of dry seed).
Factors that affect growth and development
Chung (1982) reported that longer sunshine duration seems to be more favorable for vegetative growth and morphine production in poppy.
longer sunshine increased dry matter production in poppy
The critical daylength for flowering of opium poppy is between 14 and 16 h (Gentner et al., 1975).
. Chung (1987) showed that irrigation increased dry matter production and leaf area index and delayed leaf senescence
In comparison with no irrigation, Laughlin and Chung (1992) showed that full irrigation throughout the growing season increased head yield by 95%. Although excessive water may be detrimental due to possible morphine leaching (Hofman and Menary, 1984) and promotion of fungal diseases, previous studies have shown that water stress reduces total alkaloid production in opium poppy
Mahdavi-Damghani, A., Kamkar, B., Al-Ahmadi, M., Testi, L., Munoz-Ledesma, F., & Villalobos, F. (2010, October). Water stress effects on growth, development and yield of opium poppy (Papaver somniferum L.). Retrieved from
https://www.sciencedirect.com/science/article/abs/pii/S0378377410001733
(Mahdavi-Damghani et al., 2010)
The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum
Weid, Marion, et al. “The Roles of Latex and the Vascular Bundle in Morphine Biosynthesis in the Opium Poppy, Papaver Somniferum.” PNAS, National Academy of Sciences, 21 Sept. 2004, www.pnas.org/content/101/38/13957/.
opium poppy produces approximately eighty alkaloids belonging to various tetrahydrobenzylisoquinoline-derived classes
In conclusion, two cell types, parenchyma within the vascular bundle and laticifers, are sites of the biosynthesis of isoquinoline alkaloids in P. somniferum.
The early stages of morphine biosynthesis occur in parenchyma cells surrounding laticifers and then at late stages, possibly at the level of either salutaridinol-7-O-acetate or thebaine, moves into the laticifer, which is the storage site of the morphinans thebaine, codeine, and morphine.
It has been known for over a century that morphinan alkaloids accumulate in the latex of opium poppy.
The opium poppy, Papaver somniferum, is the source of the narcotic analgesics codeine and morphine, which accumulate in specialized internal secretory cells called laticifers
The morphinan alkaloids morphine, codeine, and thebaine are found both in roots and in aerial plant parts and specifically accumulate in vesicles within laticifers
The capsule (fruit) of opium poppy is a rich source of latex and, therefore, of morphinan alkaloids.
Stem tissue that lies within 2–4 cm of the capsule is also a rich source of latex.
The opium poppy genome and morphinan production
:Morphinan-based painkillers are derived from opium poppy (Papaver somniferum L.)
the sap, known as opium, contains various alkaloids, including morphine and codeine, with effects ranging from pain relief and cough suppression to euphoria, sleepiness, and addiction.
We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively.
In the United States and Canada, more than 3000% of the estimated need is met and in Western Europe, 870% is met, whereas in China, Russia, India, and Nigeria, 16%, 8%, 4%, and 0.2%, respectively, is met
Guo, Li, et al. “The Opium Poppy Genome and Morphinan Production.” Science, American Association for the Advancement of Science, 19 Oct. 2018, science.sciencemag.org/content/362/6412/343.
(Guo et al.)
Folklore and odysseys of food and medicinal plants
Lehner, E., & Lehner, J. (2020, September 27). Folklore and odysseys of food and medicinal plants. Retrieved February 25, 2021, from
https://babel.hathitrust.org/cgi/pt?id=mdp.39015007092318&view=1up&seq=112
The red or corn poppy ( Papaver rhoeas ) and the garden or opium poppy ( Papaver somniferum ) , both native to Eurasia , have been grown in the Near East since ancient times .
inducing narcotic drugs , opium , whose name is derived from the Greek opion — poppy juice .
The juice of poppy seeds was well known to the ancient Egyptians as a sleep and dream inducing narcotic .
One of the enjoyable products of the poppy is the poppy - seed which , for generations , has been used as a condiment in bread , pastry and other baked goods
Their seeds are so tiny that one pod may contain as many as thirty thousand of them
The root of the poppy was used in ancient Assyria and Babylonia as an aphrodisiac .
The ancient Greeks used poppy seeds to relieve pain and procure sleep .
he opiate properties of poppy juice were mentioned by the Geek poet , Homer , as earuly as 850 B . C . , and the use of poppy juice for medical purposes in the form of opium wine has been noted in the writings
. The cultivation of the opium poppy spread with the march of Islam into Persia , Malaya and India
For centuries , poppies have been cultivated and opium manufactured in Bengal , the world ' s principal production center of the narcotic
The common notion that opium is typically Chinese is altogether false .
. Poppies were grown in Chinese gardens , but only as ornamental flowers , and not to provide a source of opium .
Today the three medically important and benevolent substances derived from the poppy -opium , morphine and heroin
Scientific Basis of Therapeutic Uses of Opium Poppy (Papaver
somniferum) in Ayurveda
Mani, D. and Dhawan, S.S. (2014). SCIENTIFIC BASIS OF THERAPEUTIC USES OF OPIUM POPPY (PAPAVER SOMNIFERUM) IN AYURVEDA . Acta Hortic. 1036, 175-180 DOI: 10.17660/ActaHortic.2014.1036.20
https://doi.org/10.17660/ActaHortic.2014.1036.20
It is widely grown as an ornamental flower
throughout Europe, North America, South America, and Asia.
Until now more than 40 different alkaloids have been known in this species which the most important ones are morphine, codeine, thebaine, and noscapine.
Alkaloids are affected with genetical characteristics and environmental conditions.
However it is pertinent to note that cultivation of gum varieties of opium
poppy and collection of latex is not prevalent in most of the countries except India
USES
dried latex obtained from plant capsule, is used after processing, as purified opium for pain management, treating dysentery, diarrhea etc. In Ayurveda, it is believed that each individual body has a specific PRAKRITI based on the genetic predisposition. The doshas vata, pitt and kapha when in balanced condition, symbolize a healthy body while imbalance in doshas, a disease state occurs.
In Ayurveda purified opium is used for balancing the vata and kalpa dosha but increases pitta dosha.
Small doses of opium and morphine are nerve stimulants.
Opium and morphine do not produce in animals the general calmative and hypnotic effects which characterize their use in man, but applied locally, they effectually allay pain and spasm.
It is unexcelled as a hypnotic and
sedative, and is frequently administered to relieve pain and calm excitement.
It is unexcelled as a hypnotic and sedative, and is frequently administered to relieve pain and calm excitement. For its astringent properties, it is employed in diarrhea and dysentery, and on account of its expectorant, diaphoretic, sedative and antispasmodic properties, in certain forms of cough, etc.
Morphine increases the activity and tone of the smooth muscles of gastrointestinal, biliary, and urinary tracts, causing constipation, gall bladder spasms, and urinary retention (Gennaro et al., 1956). In addition, morphine also depresses respiration and causes myosis (Gennaro et al., 1956).
Codeine is used as antitussive, analgesic, sedative, narcotic, and antiperistaltic (Gennaro et al., 1956). Thebaine, in low doses, reduces the intraocular pressure, but in higher doses causes convulsions (Gennaro et al., 1956), releases histamine (Yukio, 1957) and initiates vasodilation.
ORIGINS
From Asia Minor the Arabs traders took it to the Far Eastern countries, including India and China. P. somniferum is sometimes found apparently wild in Britain.
P. somniferum is originally a native of the warmer parts of Western Asia from where it was taken to Greece.
Primary Alkaloids
Morphine, codeine, thebaine, narcotine, papaverine, narceine, pseudomorphine, cryptopine, protopine, hydrocatarnine, laudanine, laudanosine, meconidine, rhoeadine, meconidine, codamine, nascopine, lanthopine, xanthaline
Very recently Prof. M.H Zenk and Tony Kutchan, Donald Danfold Plant Science Center have shown that the human brain biosynthesize morphine in trace amount using a biosynthetic pathway i.e. is distant from the one operation in the poppy plant.
Symptoms of opium poisoning
TANDRA (drowsiness) 2. SANYAS (numbness) 3. SWASAVRODHA (rRespiratory chock) 4. NINDRA (sedation) 5. AVASADA (lessitude) 6. MIRTYU (death)
Method of Opium Purification
Dissolve the opium in water and filter with cloth and make concentrate by boiling in heat and mix twenty one times with ginger juice seven Bhawnas concentrate and dry than used for medicine.
Papaver somniferum L.
Duke, James A. “Papaver Somniferum L.” Papaver Somniferum, Purdue University , 7 Jan. 1998, hort.purdue.edu/newcrop/duke_energy/Papaver_somniferum.html.
Cultivation
seed sown in shallow furrows, at rate of 4–6 kg/ha.
in some areas poppy seed, mixed with sand, is often broadcast over tilled fields in early autumn at rate of about 0.5 kg/ha, as in Asia Minor
Seeds germinate best at 15°C and are less sensitive to temperature than most poppy species.
Then fields are weeded in the spring when the poppy has grown to about 15 cm tall, and plants are thinned then to stand about 60 cm apart.
They flower in April and May and the capsules are ripe in June to July
Optimum yields are obtained when plants are spaced 10 cm between plants and rows 32 cm apart, thus allowing space for mechanical cultivation.
Yields of seeds are slightly higher when plants are spaced 30 cm apart than when 40 cm apart. Thinning and spacing do not affect the oil content of the seeds. Fertile soil is essential for good growth and land should be fertilized accordingly.
Climate Preference
Soils with pH neutral or slightly alkaline preferable.
Deep, warm, moderately moist, medium heavy soils, well cultivated, and limed meet the requirements for poppy growing.
Thrives in rich, well-manured soil, in hot to warm regions
poppy is reported to tolerate annual precipitation of 3.1 to 17.3 dm
annual temperature of 5.6 to 23.5°C
and pH of 4.9 to 8.
It does poorly in the humid tropics.
The Impact of Morphine on the Characteristics and Function Properties of Human Mesenchymal Stem Cells
Holan, V., Cechova, K., Zajicova, A. et al. The Impact of Morphine on the Characteristics and Function Properties of Human Mesenchymal Stem Cells. Stem Cell Rev and Rep 14, 801–811 (2018).
https://doi.org/10.1007/s12015-018-9843-8
Impact of opioids on tissues
The prolonged use of morphine
impaired angiogenesis and the activation of endothelial progenitor cells and negatively influenced wound repair
Using an experimental model of wound closure it has shown that topical opioids impaired wound healing and caused a detrimental effect on the healing proces
At low concentrations (2 and 20 μM) morphine significantly enhanced adipogenic differentiation, but at the high concentration (200 μM) the differentiation of MSCs was inhibited. The osteogenic differentiation was inhibited by morphine in a dosedependent manner
The production of VEGF and LIF were significantly decreased in a dose-dependent manner in the presence of morphine (Fig. 6D and E). HGF is a factor, which is produced constitutively by untreated MSCs and its production is rather decrerased in the presence of proinflammatory cytokines. F
Here we showed that morphine, in higher concentrations, significantly enhances the expression of genes for potent intracellular immunomodulatory molecules IDO and COX-2 or for membrane molecules PD-L1 and TSG-6.
Morphine binds and acts primarily on cells of the nervous system, but multiple other cell types express OR and their functions are modified by this drug.
MSCs represent another type of stem cells, which are present in nearly all tissues of the body and contribute to tissue regeneration and healing by their differentiation potential, potent immunoregulatory properties and by the production of numerous growth and trophic factors
Impaired tissue healing observed after morphine administration or in opioid addicts suggests the possibility of the harmful impacts of morphine on stem cells and their functions
It suggests that morphine inhibit MSC proliferation, but metabolic pathways are not affected. Another property of MSCs is their ability to differentiate into adipocytes and osteoblasts. Using real-time PCR we showed that the expression of genes for adipocyte markers ADPC and PPARγ or osteoblast marker OPN was modified in MSCs growing in differentiation-inducing media in the presence of morphine.
The inhibition of the expression of regulatory molecule CD146 and the decreased production of growth factors VEGF, HGF and LIF suggests that this inhibition could be a reason for the impaired and slowed down tissue healing which is regularly observed after morphine administration.
CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016
Deborah Dowell, MD. “CDC Guideline for Prescribing Opioids for Chronic Pain, 2016.” JAMA, JAMA Network, 19 Apr. 2016, jamanetwork.com/journals/jama/article-abstract/2503508.
(Deborah Dowell)
when opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible.
Opioids should be used only when benefits for pain and function are expected to outweigh risks.
Of primary importance, nonopioid therapy is preferred for treatment of chronic pain.
From 1999 to 2014, more than 165 000 persons died of overdose related to opioid pain medication in the United States.8 In 2013 alone, an estimated 1.9 million persons abused or were dependent on prescription opioid pain medication.
Adverse Effects
Long-term opioid therapy was associated with an increased risk of an opioid abuse or dependence diagnosis (as defined by ICD-9-CM codes) vs no opioid prescription.
Long-term opioid therapy was associated with problematic patterns of opioid use leading to clinically significant impairment or distress. Varying terminology has been used to reflect this pattern, including “addiction” (more informally), “opioid abuse and opioid dependence” (per Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] [DSM-IV] or International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]), and “opioid use disorder” (per DSM-5
In primary care settings, prevalence of opioid dependence (using DSM-IV criteria) ranged from 3% to 26%.
Factors associated with increased risk of misuse included history of substance use disorder, younger age, major depression, and use of psychotropic medications
Studies examining patients who underwent low-risk surgery or experienced low back pain from injury revealed that opioid therapy prescribed for acute pain was associated with greater likelihood of long-term use.
Compared with dosages of 1 to <20 MME per day, dosages of 50 to <100 MME per day were found to increase risks for opioid overdose by factors of 1.920 to 4.6,22
Veterans Health Administration patients with chronic pain who died of overdoses related to opioids were prescribed higher mean opioid dosages (98 MME/d) than controls (48 MME/d)27; above 200 MME per day, mortality rates continue to increase more gradually.
POPPY LATEX
opioid receptors
GI muscle involvement
