title: Iran hostage crisis

text: Some of the ex-hostages and their families received payments, but then Justice Department lawyers interpreted the law to allow 9/11 family members to get a judgment against Iran as well and to apply to the USVSST fund. Later, victims of the 1983 Beirut bombings also instituted claims against USVSST fund. Due to depletion of the fund, by February 2019, only 17.8% of the legislated amount had been paid to the freed hostages and their direct families.


title: Iran hostage crisis

text: The timing of the release of the hostages gave rise to allegations that representatives of Reagan's presidential campaign had conspired with Iran to delay the release until after the 1980 United States presidential election to thwart Carter from pulling off an "October surprise". In 1992, Gary Sick, the former national security adviser to Ford and Carter, presented the strongest accusations in an editorial that appear in "The New York Times", and others, including former Iranian president Abolhassan Banisadr, repeated and added to them. This alleged plot to influence the outcome of the 1980 United States presidential election between Carter and Reagan became known as the October Surprise conspiracy theory.


title: Iran hostage crisis

text: After twelve years of varying media attention, both houses of the United States Congress held separate inquiries and concluded that credible evidence supporting the allegation was absent or insufficient.


title: Iran hostage crisis

text: Over 80 songs which are about the Iran hostage crisis or contain references to it have been released.


title: Iran hostage crisis

text: The 2012 Hollywood movie "Argo," which won the Academy Award for Best Picture, was based on the Canadian Caper rescue.


title: Iran hostage crisis

text: In the video game campaign of , CIA agents Russell Adler, Frank Woods and Alex Mason are sent to target two Iranian diplomats due to their roles in the crisis. They theorize that the KGB spy codenamed Perseus was responsible for the instigation of the crisis.


title: Iran hostage crisis

text: Records of the Prime Minister's Office, Correspondence & Papers; 1979–97 at discovery.nationalarchives.gov.uk: IRAN. Internal situation in Iran; Attack on British Embassy; Hostage-taking at US Embassy; Freezing of Iranian Assets; US Mission to release hostages; Relations with US & UK following hostage taking at US Embassy.


title: Poutine

text: Poutine () is a dish of french fries and cheese curds topped with a brown gravy. It emerged in Quebec, in the late 1950s in the Centre-du-Québec region, though its exact origins are uncertain and there are several competing claims regarding its invention. For many years it was perceived negatively and mocked, and even used by some to stigmatize Quebec society. Poutine later became celebrated as a symbol of Québécois culture and the province of Quebec. It has long been associated with Quebec cuisine, and its rise in prominence has led to popularity throughout the rest of Canada, in the northern United States, and internationally.


title: Poutine

text: Annual poutine celebrations occur in Montreal, Quebec City, and Drummondville, as well as Toronto, Ottawa, New Hampshire, and Chicago. It has been called "Canada's national dish", though some believe this labelling represents cultural appropriation of the Québécois or Quebec's national identity. Many variations on the original recipe are popular, leading some to suggest that poutine has emerged as a new dish classification in its own right, as with sandwiches and dumplings.


title: Poutine

text: The dish was created in the Centre-du-Québec area in the late 1950s. Several restaurants in the area claim to be the originators of the dish, but no consensus exists.


title: Poutine

text: According to Canadian food researcher Sylvain Charlebois, while Warwick is the birthplace of poutine, Drummondville's Jean-Paul Roy is the true inventor since le Roy Jucep was the first to sell poutine with three combined ingredients, in 1964. "The Oxford Companion to Cheese" takes a different perspective, stating that the inventors were not chefs but the customers who chose to add cheese curds to their fries.


title: Poutine

text: Poutine was consumed in small "greasy spoon" diners (commonly known in Quebec as "cantines" or "casse-croûtes"), pubs, at roadside chip wagons (commonly known as "cabanes à patates", literally "potato shacks") and in hockey arenas. For decades it remained a country snack food in Quebec's dairy region, due to the narrow freshness window of cheddar cheese curds. In 1969, poutine was brought to Quebec City in Ashton Leblond's food truck (a business which grew into the Chez Ashton fast-food chain). In the early 1970s, La Banquise began serving poutine in Montreal, followed by the Burger King chain in 1983. Others that followed used inferior cheese and the dish's reputation declined. Poutine was largely perceived as an unsophisticated backwoods creation or unhealthy junk food to be consumed after a night of drinking.


title: Poutine

text: Montreal chefs would make poutine to feed their staff but had not dared to put it on their menus. In the 1990s, attempts were made to elevate the dish by using baked potatoes and duck stock. In November 2001, Martin Picard of bistro Au Pied de Cochon began serving a foie gras poutine which was praised by customers and food critics. This influenced chefs in Toronto and Vancouver to feature poutine on upscale menus. Chef Mark McEwan served lobster poutine at his Bymark eatery, and chef Jamie Kennedy served braised beef poutine at his eponymous restaurant. Over the next decade, poutine gained acceptance and popularity in all types of restaurants, from haute cuisine to fast food, and spread across Canada and internationally.


title: Poutine

text: The "Dictionnaire historique du français québécois" lists 15 meanings of "poutine" in Québécois and Acadian French, most of which are for kinds of food; the word "poutine" in the meaning "fries with cheese and gravy" is dated to 1982 in English. Other senses of the word have been in use since at least 1810.


title: Poutine

text: According to Merriam-Webster, a popular etymology is that "poutine" is from a Québécois slang word meaning "mess", and that others attribute it to the English word "pudding". The exact provenance of the word "poutine" is uncertain.


title: Poutine

text: The "Dictionnaire historique" mentions the possibility that the form "poutine" is simply a gallicization of the word "pudding". However, it considers it more likely that it was inherited from regional languages spoken in France, and that some of its meanings resulted from the later influence of the similar-sounding English word "pudding". It cites the Provençal forms "poutingo" "bad stew" and "poutité" "hodgepodge" or "crushed fruit or foods"; "poutringo" "mixture of various things" in Languedocien; and "poutringue" or "potringa" "bad stew" in Franche-Comté as possibly related to "poutine". The meaning "fries with cheese and gravy" of "poutine" is among those held as probably unrelated to "pudding", provided the latter view is correct.


title: Poutine

text: To maintain the texture of the fries, the cheese curds and gravy are added immediately before serving the dish. The hot gravy is usually poured over room-temperature cheese curds, so they are warmed without melting completely. The thin gravy allows all the fries to be coated. The serving dish typically has some depth to act as a basket for the fries so that they retain their heat. It is important to control the temperature, timing, and the order in which the ingredients are added to obtain the right food textures—an essential part of the experience of eating poutine.


title: Poutine

text: Freshness and juiciness of the curds is essential. Air and moisture seep out of the curds over time, altering their acidity level. This causes proteins to lose their elasticity, and the curds to lose their complex texture and characteristic squeaky sound when chewed. The curds should be less than a day old, which requires proximity to a dairy. While Montreal is from a cheese plant in Mirabel, restaurants and specialty cheese shops outside of dairy regions may be unable to sell enough curds to justify the expense of daily deliveries. Furthermore, Canadian food safety practices require curds to be refrigerated within 24 hours, which suppresses the properties of their texture. This has resulted in "poutineries" which specialize in the dish; busy poutineries may use of curds per day. Poutineries which are too distant from dairies may make their own cheese curds on site, in batches every few hours, to ensure a fresh and steady supply.


title: Poutine

text: The texture, temperature and viscosity of poutine's ingredients differ and continuously change as the food is consumed, making it a dish of highly dynamic contrasts. Strengthening these contrasts, superior poutines are identified by the crispiness of the fries, freshness of the curds, and a unifying gravy. Even small variations in ingredients or preparation—the oil used for frying, the origin of the curds, or spices in the gravy—can result in a distinctly different experience of eating the poutine.


title: Poutine

text: Some recipes eliminate the cheese, but most Québécois would call such a dish a "frite sauce" (), not poutine. When curds are unavailable, mozzarella cheese may be an acceptable alternative. Shredded mozzarella is commonly used in Saskatchewan. Sweet potato may be used as a healthier alternative to french fries, adding more dietary fibre and vitamins.


title: Poutine

text: Poutineries, like Montreal's La Banquise, which is credited for much of the innovation and popularization of poutine, have dozens of varieties of poutine on their menus. Many of these are based on the traditional recipe with an added meat topping such as sausage, chicken, bacon, brisket, or Montreal-style smoked meat, with the gravy adjusted for balance. The Quebec City-based chain Chez Ashton is known for its poutine Galvaude (topped with chicken and green peas) and Dulton (with ground beef). New variations are frequently introduced. Pulled pork was popular around 2013, followed a couple years later by Asian-fusion poutines.


title: Poutine

text: Montreal's high immigrant population has led to many takes on the dish inspired by other cuisines, such as Haitian, Mexican, Portuguese, Indian, Japanese, Greek, Italian and Lebanese. These poutines may bear little resemblance to the traditional recipe. They replace some or all of the ingredients but maintain the dynamic contrasts of textures and temperatures with a crispy element, a dairy or dairy-like element, and a unifying sauce. Many variations on the original recipe are popular, leading some to suggest that poutine has emerged as a new dish classification in its own right, as with sandwiches, dumplings, soups, and flatbreads.


title: Poutine

text: Poutineries will frequently offer limited-time promotional specials, such as a Thanksgiving poutine with turkey, stuffing and cranberry sauce. In anticipation of the legalization of cannabis in Canada, Montreal's Le Gras Dur served a "pot poutine" with a gravy that included hemp protein, hemp seeds and hemp oil, offered with a joint-like roll of turkey, wild mushrooms and arugula.


title: Poutine

text: Gourmet poutine with three-pepper sauce, merguez sausage, foie gras or caviar and truffle can be found. This is a trend that began in the 1990s and is credited to David McMillan of Montreal's Joe Beef and Globe restaurants. Savoury sauces like Moroccan harissa, lobster sauce, and red-wine veal "jus" have been used to complement artisanal cheeses and rich ingredients.


title: Poutine

text: Chains such as Smoke's Poutinerie, New York Fries, McDonald's, Wendy's, A&W, KFC, Burger King, Harvey's, Mary Brown's, Arby's, and Wahlburgers restaurants also sell versions of poutine in Quebec and the rest of Canada (although not always country-wide). Tim Hortons began selling poutine in 2018. Fast-food combination meals in Canada often have the options to have french fries "poutinized" by adding cheese curds (or shredded cheese in the Prairies and Western Canada) and gravy, or substituting a poutine for a fries side.


title: Poutine

text: Poutine is found in the northern border regions of the United States, including New England and the larger Northeast, the Pacific Northwest, and the Upper Midwest. These regions offer further variations of the basic dish, usually by utilizing cheeses other than fresh curds, which are not widely available in the US. Wendy's fast food chain offers poutine in the form of "Baconator Fries", which is fried thin sticks of potato with melted yellow cheese and bits of bacon. In the country culture, a mixed fry can also come with cooked ground beef on top and is referred to as a hamburger mix, though this is less popular than a regular mix. In the Pacific Northwest, one variation replaces the gravy with chowder featuring local seafood.


title: Poutine

text: Disco fries, french fries typically covered in mozzarella cheese and brown gravy, were popularized in New Jersey in the 1990s. They gained their name in the 1970s for being a favourite of late-night diners, who often came from dancing at disco clubs. The dish is also popular in New Orleans including variations called Cajun poutine.


title: Poutine

text: A dish of cheese, chips and gravy was proposed to replace the Isle of Mann's traditional national dish of boiled potatoes and herring in 2018. It is made of french fries and grated Manx cheddar cheese melted by a hot beef gravy, and became popular in the 1990s. It is unclear whether this dish is an independent invention or a poutine variant.


title: Poutine

text: Poutine spread to the United Kingdom, Japan, Korea and Russia, where it has been referred to as "Raspoutine". The first poutinerie in Paris, La Maison de la Poutine, opened in 2017 and quickly gained attention from mainstream media and gastronomers.


title: Poutine

text: A cultural marker, poutine had long been Quebec's adored junk food before spreading across the rest of Canada and the United States. It had by then made inroads with food critics and established culinary circles, challenging its junk food status. Food critic Jacob Richler noted in 2012 that Canadian dishes are too similar to their European roots to be considered original, with the exception of poutine, which he credited as the country's most famous culinary creation. In May 2014, the word "poutine" was added to the "Merriam-Webster Dictionary" of the English language.


title: Poutine

text: In 2007, the Canadian Broadcasting Corporation (CBC) declared the results of an online survey on the greatest Canadian inventions, in which poutine ranked at  10. "Maclean's" 2017 survey of "favourite iconic Canadian food" placed poutine first with 21% of respondents, ahead of maple syrup with 14%. By 2011, media outlets were reporting 11 April as National Poutine Day.


title: Poutine

text: In March 2016, poutine was served at the White House during the first state dinner hosted by President Barack Obama and Canada's Prime Minister Justin Trudeau. Poutine has been a highlight of Canada Day celebrations in Trafalgar Square in London, England, for several years, and was a comfort food for the local community after the 2013 Lac-Megantic derailment. It was served at the inaugural Canadian Comedy Awards.


title: Poutine

text: The first poutine festival was held in Warwick, Quebec, in 1993. This annual event expanded to become the largest cheese festival in Canada. In 2014, it was moved to the larger town of Victoriaville. Montreal has hosted La Poutine Week, an annual festival, food tour, and competition held 1–7 February, since 2013. It spread across Canada and internationally, and by 2021 had become the largest poutine festival in the world, with over 700 restaurants serving more than 350,000 poutines. Poutine festivals are also held in Drummondville (since 2008), Ottawa-Gatineau, Toronto, Calgary, Vancouver, Quebec City and Sherbrooke. In the US, major festivals have been held in Chicago, IL, Manchester, NH, Knoxville, TN, and in Rhode Island.


title: Poutine

text: Since 2010, the International Federation of Competitive Eating (IFCE) has held a world poutine-eating championship sponsored by Toronto-based chain Smoke's Poutinerie. There was criticism that the inaugural contest was held outside of Quebec and excluded Québécois. The IFCE stated that Montreal poutineries had not expressed any interest in holding the competition. Regulations for contests in Quebec make it difficult to include the province, which is often absent from national contests. Smoke's has since sponsored a cross-Canada poutine eating tour. In 2011, chef Chuck Hughes won on "Iron Chef America" (episode 2 of ) by beating Bobby Flay with a plate of lobster poutine.


title: Poutine

text: Jones Soda Co., originally a Canadian company now based in the US, created a poutine-flavoured limited-edition soft drink in 2013, which received international pop culture attention. Bacon-poutine was one of four flavours selected as a finalist in the 2014 Lay's Canada Do Us A Flavour potato chip contest. Though it did not win, Lay's later added a bacon-poutine variety in its Canada entry for the World Flavourites. Loblaws' President's Choice and Ruffles brands also offer poutine-flavoured potato chips in Canada.


title: Poutine

text: Giapos Ice Cream of New Zealand has served a "poutine ice cream" of oolong matcha tea, ice cream and caramel sauce over hand-cut fries since 2017.


title: Poutine

text: In a 2018 promotional campaign for the film "Crazy Rich Asians", "the world's richest poutine" was created with wagyu steak, lobster, truffles, shiitake and chanterelle mushrooms, edible orchids, and gold flakes, priced just under $450.


title: Poutine

text: Joel Edmundson, of the 2018–19 National Hockey League champion team St. Louis Blues, ate poutine from the Stanley Cup during celebrations attended by over 4,000 fans in his hometown of Brandon, Manitoba. Mathieu Joseph, a Chambly, Quebec native who won the Cup with the Tampa Bay Lightning in 2020 and 2021, also ate poutine from the Cup during a celebration with the Cup in 2021.


title: Poutine

text: The social status of poutine has evolved dramatically since its origins in rural Quebec in the 1950s. The dish was long mocked as a culinary invention and used as a means of stigmatization by non-Québécois against Quebec society to reduce its legitimacy. While the first generations that suffered from the poutine stigma opted to disidentify from the dish, Quebec youth have recently been operating a reappropriation of poutine to positively revalue the dish as a symbol of Quebecois cultural pride. Today, the dish is celebrated in many annual poutine festivals in Quebec, the rest of Canada, and in the United States.


title: Poutine

text: The evolution of the different symbols associated with poutine was first studied in "Maudite Poutine!" by Charles-Alexandre Théorêt. Théorêt revisited many of these stigmas in an interview given at "Tout le monde en parle" on 11 November 2007.


title: Poutine

text: As poutine gained popularity outside Quebec provincial borders in the mid-2000s, the dish gradually stopped being mocked and was eventually introduced into the popular discourse as a symbol of Canadian identity. Today, the dish is often presented as being of Canadian cuisine, even as Canada's national dish. Nicolas Fabien-Ouellet, the author of "Poutine Dynamics" (a peer-reviewed article published in the journal "CuiZine") has suggested that this "Canadization" of poutine constitutes cultural appropriation. This appropriation is not linked to its preparation or consumption outside Quebec per se, but strictly to its presentation as a Canadian dish instead of a Québécois dish. Fabien-Ouellet explains:


title: Poutine

text: Fabien-Ouellet has given many talks about the canadianization and cultural appropriation of poutine, notably in "The New York Times", "National Post", "Vice", Radio-Canada, , , , Vermont Public Radio, HuffPost, "La Presse", and "Le Journal de Montréal".


title: Poutine

text: In a "Talking to Americans" segment on the Canadian mock television news show "This Hour Has 22 Minutes", during the 2000 US election, comedian Rick Mercer posed as a reporter and asked US politicians what they thought of "Prime Minister Jean Poutine" and his endorsement of George W. Bush for president. (The Prime Minister of Canada at the time was Jean Chrétien.) None of the interviewees noticed the insertion of "Poutine" and Bush pledged to "work closely" with Mr. Poutine. A few years later, when Bush made his first official visit to Canada as president, he joked in a speech, "There's a prominent citizen who endorsed me in the 2000 election, and I wanted a chance to finally thank him [...] I was hoping to meet Jean Poutine." The remark was met with laughter and applause.


title: Poutine

text: In French, Russian president Vladimir Putin's surname is spelled "Poutine", with the two having identical pronunciation. The similarity has been a source of confusion; in commenting on the "Talking to Americans" prank on Bush, "Washington Post" columnist Al Kamen mistakenly believed that Mercer's fictional Jean Poutine was a reference to Putin. In 2017, Russian-themed poutinerie Vladimir Poutine opened in Montreal, with dishes named for political figures from Rasputin to Donald Trump. In the week following the 2022 Russian invasion of Ukraine, frequent insults and threats were received by the three Maison de la Poutine restaurants in Paris, some stating a belief that they worked for the Russian state. Another poutinerie in Lyon changed the name of its 20-year signature dish, Vladimir poutine, stating that it "was no longer funny". In Quebec, Le Roy Jucep announced that it was retiring the word "poutine" in support of Ukraine and reverted to "fromage-patate-sauce" on its menus and branding.


title: Poutine

text: During the 2011 Canadian federal election, some voters reported receiving robocalls claiming to be from Elections Canada, from a phone number registered to "Pierre Poutine". The calls targeted voters who had previously indicated they would not vote for the Conservative Party. The calls, made on election day or the day before, falsely advised voters that their polling station had been changed, in an attempt to prevent them from voting. The allegations became known as the Robocall scandal, and subsequent investigation by the Royal Canadian Mounted Police resulted in Michael Sona, a junior Conservative Party staffer, being convicted of violating the "Elections Act".


title: Poutine

text: Belgian Prime Minister Charles Michel had a Canadian lunch with counterpart Justin Trudeau on 16 June 2017, during which they ate hotdogs and poutine. Michel tweeted later that this was "A great way to meet a dear friend though our fries are better", referring to the popular claim that fries were originally invented in Belgium. In 2019, Canada attempted to garner support for its campaign for a non-permanent United Nations Security Council seat in the following year's election by serving poutine to UN diplomats.


title: Prostate

text: The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physiologically. Anatomically, the prostate is found below the bladder, with the urethra passing through it. It is described in gross anatomy as consisting of lobes and in microanatomy by zone. It is surrounded by an elastic, fibromuscular capsule and contains glandular tissue as well as connective tissue.


title: Prostate

text: The prostate glands produce and contain fluid that forms part of semen, the substance emitted during ejaculation as part of the male sexual response. This prostatic fluid is slightly alkaline, milky or white in appearance. The alkalinity of semen helps neutralize the acidity of the vaginal tract, prolonging the lifespan of sperm. The prostatic fluid is expelled in the first part of ejaculate, together with most of the sperm, because of the action of smooth muscle tissue within the prostate. In comparison with the few spermatozoa expelled together with mainly seminal vesicular fluid, those in prostatic fluid have better motility, longer survival, and better protection of genetic material.


title: Prostate

text: Disorders of the prostate include enlargement, inflammation, infection, and cancer. The word prostate comes from Ancient Greek προστάτης, "prostátēs", meaning "one who stands before", "protector", "guardian", with the term originally used to describe the seminal vesicles.


title: Prostate

text: The prostate is a gland of the male reproductive system. In adults, it is about the size of a walnut, and has an average weight of about 11 grams, usually ranging between 7 and 16 grams. The prostate is located in the pelvis. It sits below the urinary bladder and surrounds the urethra. The part of the urethra passing through it is called the prostatic urethra, which joins with the two ejaculatory ducts. The prostate is covered in a surface called the "prostatic capsule" or "prostatic fascia".


title: Prostate

text: The internal structure of the prostate has been described using both lobes and zones. Because of the variation in descriptions and definitions of lobes, the zone classification is used more predominantly.


title: Prostate

text: The prostate has been described as consisting of three or four zones. Zones are more typically able to be seen on histology, or in medical imaging, such as ultrasound or MRI. The zones are:


title: Prostate

text: The "lobe" classification describes lobes that, while originally defined in the fetus, are also visible in gross anatomy, including dissection and when viewed endoscopically. The five lobes are the anterior lobe or isthmus, the posterior lobe, the right and left lateral lobes, and the middle or median lobe.


title: Prostate

text: Inside of the prostate, adjacent and parallel to the prostatic urethra, there are two longitudinal muscle systems. On the front side (ventrally) runs the "urethral dilator" ("musculus dilatator urethrae"), on the backside (dorsally) runs the muscle switching the urethra into the ejaculatory state ("musculus ejaculatorius").


title: Prostate

text: The prostate receives blood through the inferior vesical artery, internal pudendal artery, and middle rectal arteries. These vessels enter the prostate on its outer surface where it meets the bladder, and travel forward to the apex of the prostate. Both the inferior vesical and the middle rectal arteries often arise together directly from the internal iliac arteries. On entering the bladder, the inferior vesical artery splits into a urethral branch, supplying the urethral prostate; and a capsular branch, which travels around the capsule and has smaller branches which perforate into the prostate.


title: Prostate

text: The veins of the prostate form a network – the prostatic venous plexus, primarily around its front and outer surface. This network also receives blood from the deep dorsal vein of the penis, and is connected via branches to the vesical plexus and internal pudendal veins. Veins drain into the vesical and then internal iliac veins.


title: Prostate

text: The lymphatic drainage of the prostate depends on the positioning of the area. Vessels surrounding the vas deferens, some of the vessels in the seminal vesicle, and a vessel from the posterior surface of the prostate drain into the external iliac lymph nodes. Some of the seminal vesicle vessels, prostatic vessels, and vessels from the anterior prostate drain into internal iliac lymph nodes. Vessels of the prostate itself also drain into the obturator and sacral lymph nodes.


title: Prostate

text: The prostate consists of glandular and connective tissue. Tall column-shaped cells form the lining (the epithelium) of the glands. These form one layer or may be pseudostratified. The epithelium is highly variable and areas of low cuboidal or flat cells can also be present, with transitional epithelium in the outer regions of the longer ducts. The glands are formed as many follicles, which in drain into canals and subsequently 12–20 main ducts, These in turn drain into the urethra as it passes through the prostate. There are also a small amount of flat cells, which sit next to the basement membranes of glands, and act as stem cells.


title: Prostate

text: The connective tissue of the prostate is made up of fibrous tissue and smooth muscle. The fibrous tissue separates the gland into lobules. It also sits between the glands and is composed of randomly orientated smooth-muscle bundles that are continuous with the bladder.


title: Prostate

text: About 20,000 protein coding genes are expressed in human cells and almost 75% of these genes are expressed in the normal prostate. About 150 of these genes are more specifically expressed in the prostate, with about 20 genes being highly prostate specific. The corresponding specific proteins are expressed in the glandular and secretory cells of the prostatic gland and have functions that are important for the characteristics of semen, including prostate-specific proteins, such as the prostate specific antigen (PSA), and the Prostatic acid phosphatase.


title: Prostate

text: In the developing embryo, at the hind end lies an inpouching called the cloaca. This, over the fourth to the seventh week, divides into a urogenital sinus and the beginnings of the anal canal, with a wall forming between these two inpouchings called the urorectal septum. The urogenital sinus divides into three parts, with the middle part forming the urethra; the upper part is largest and becomes the urinary bladder, and the lower part then changes depending on the biological sex of the embryo.


title: Prostate

text: The prostatic part of the urethra develops from the middle, pelvic, part of the urogenital sinus, which is of endodermal origin. Around the end of the third month of embryonic life, outgrowths arise from the prostatic part of the urethra and grow into the surrounding mesenchyme. The cells lining this part of the urethra differentiate into the glandular epithelium of the prostate. The associated mesenchyme differentiates into the dense connective tissue and the smooth muscle of the prostate.


title: Prostate

text: Condensation of mesenchyme, urethra, and Wolffian ducts gives rise to the adult prostate gland, a composite organ made up of several tightly fused glandular and non-glandular components. To function properly, the prostate needs male hormones (androgens), which are responsible for male sex characteristics. The main male hormone is testosterone, which is produced mainly by the testicles. It is dihydrotestosterone (DHT), a metabolite of testosterone, that predominantly regulates the prostate. The prostate gland enlarges over time, until the fourth decade of life.


title: Prostate

text: The prostate secretes fluid which becomes part of semen. Semen is the fluid emitted (ejaculated) by males during the sexual response. When sperm is emitted, it is transmitted from the vas deferens into the male urethra via the ejaculatory ducts, which lie within the prostate gland. Ejaculation is the expulsion of semen from the urethra. Semen is moved into the urethra following contractions of the smooth muscle of the vas deferens and seminal vesicles, following stimulation, primarily of the glans penis. Stimulation sends nerve signals via the internal pudendal nerves to the upper lumbar spine; the nerve signals causing contraction act via the hypogastric nerves. After traveling into the urethra, the seminal fluid is ejaculated by contraction of the bulbocavernosus muscle. The secretions of the prostate include proteolytic enzymes, prostatic acid phosphatase, fibrinolysin, zinc, and prostate-specific antigen. Together with the secretions from the seminal vesicles, these form the major fluid part of semen.


title: Prostate

text: It is possible for some men to achieve orgasm solely through stimulation of the prostate gland, such as via prostate massage or anal intercourse. This has led to the area of the rectal wall adjacent to the prostate to be popularly (yet inaccurately) referred to as the "male G-spot".


title: Prostate

text: The prostate's changes of shape, which facilitate the mechanical switch between urination and ejaculation, are mainly driven by the two longitudinal muscle systems running along the prostatic urethra. These are the "urethral dilator" ("musculus dilatator urethrae") on the urethra's front side, which contracts during urination and thereby shortens and tilts the prostate in its vertical dimension thus widening the prostatic section of the urethral tube, and the muscle switching the urethra into the ejaculatory state ("musculus ejaculatorius") on its backside.


title: Prostate

text: In case of an operation, e.g. because of benign prostatic hyperplasia (BPH), damaging or sparing of these two muscle systems varies considerably depending on the choice of operation type and details of the procedure of the chosen technique. The effects on postoperational urination and ejaculation vary correspondingly. (See also: Surgery for benign prostatic hyperplasia).


title: Prostate

text: Prostatitis is inflammation of the prostate gland. It can be caused by infection with bacteria, or other noninfective causes. Inflammation of the prostate can cause painful urination or ejaculation, groin pain, difficulty passing urine, or constitutional symptoms such as fever or tiredness. When inflamed, the prostate becomes enlarged and is tender when touched during digital rectal examination. The bacteria responsible for the infection may be detected by a urine culture.


title: Prostate

text: Acute prostatitis and chronic bacterial prostatitis are treated with antibiotics. Chronic non-bacterial prostatitis, or male chronic pelvic pain syndrome is treated by a large variety of modalities including the medications alpha blockers, nonsteroidal antiinflammatories and amitriptyline, antihistamines, and other anxiolytics. Other treatments that are not medications may include physical therapy, psychotherapy, nerve modulators, and surgery. More recently, a combination of trigger point and psychological therapy has proved effective for category III prostatitis as well.


title: Prostate

text: An enlarged prostate is called prostatomegaly, with benign prostatic hyperplasia (BPH) being the most common cause. BPH refers to an enlargement of the prostate due to an increase in the number of cells that make up the prostate () from a cause that is not a malignancy. It is very common in older men. It is often diagnosed when the prostate has enlarged to the point where urination becomes difficult. Symptoms include needing to urinate often (urinary frequency) or taking a while to get started (urinary hesitancy). If the prostate grows too large, it may constrict the urethra and impede the flow of urine, making urination painful and difficult, or in extreme cases completely impossible, causing urinary retention. Over time, chronic retention may cause the bladder to become larger and cause a backflow of urine into the kidneys (hydronephrosis).


title: Prostate

text: BPH can be treated with medication, a minimally invasive procedure or, in extreme cases, surgery that removes the prostate. In general, treatment often begins with an alpha-1 adrenergic receptor antagonist medication such as tamsulosin, which reduces the tone of the smooth muscle found in the urethra that passes through the prostate, making it easier for urine to pass through. For people with persistent symptoms, procedures may be considered. The surgery most often used in such cases is transurethral resection of the prostate, in which an instrument is inserted through the urethra to remove prostate tissue that is pressing against the upper part of the urethra and restricting the flow of urine. Minimally invasive procedures include transurethral needle ablation of the prostate and transurethral microwave thermotherapy. These outpatient procedures may be followed by the insertion of a temporary stent, to allow normal voluntary urination, without exacerbating irritative symptoms.


title: Prostate

text: Prostate cancer is one of the most common cancers affecting older men in the UK, US, Northern Europe and Australia, and a significant cause of death for elderly men worldwide. Often, a person does not have symptoms; when they do occur, symptoms may include urinary frequency, urgency, hesitation and other symptoms associated with BPH. Uncommonly, such cancers may cause weight loss, retention of urine, or symptoms such as back pain due to lesions that have spread outside of the prostate.


title: Prostate

text: A digital rectal examination and the measurement of a prostate-specific antigen (PSA) level are usually the first investigations done to check for prostate cancer. PSA values are difficult to interpret, because a high value might be present in a person without cancer, and a low value can be present in someone with cancer. The next form of testing is often the taking of a biopsy to assess for tumour activity and invasiveness. Because of the significant risk of overdiagnosis with widespread screening in the general population, prostate cancer screening is controversial. If a tumour is confirmed, medical imaging such as an MRI or bone scan may be done to check for the presence of tumour in other parts of the body.


title: Prostate

text: Prostate cancer that is only present in the prostate is often treated with either surgical removal of the prostate or with radiotherapy or by the insertion of small radioactive particles of iodine-125 or palladium-103, called brachytherapy. Cancer that has spread to other parts of the body is usually treated also with hormone therapy, to deprive a tumour of sex hormones (androgens) that stimulate proliferation. This is often done through the use of GnRH analogues or agents that block the receptors that androgens act at, such as bicalutamide; occasionally, surgical removal of the testes may be done instead. Cancer that does not respond to hormonal treatment, or that progresses after treatment, might be treated with chemotherapy such as docetaxel. Radiotherapy may also be used to help with pain associated with bony lesions.


title: Prostate

text: Sometimes, the decision may be made not to treat prostate cancer. If a cancer is small and localised, the decision may be made to monitor for cancer activity at intervals ("active surveillance") and defer treatment. If a person, because of frailty or other medical conditions or reasons, has a life expectancy less than ten years, then the impacts of treatment may outweigh any perceived benefits.


title: Prostate

text: Surgery to remove the prostate is called prostatectomy, and is usually done as a treatment for cancer limited to the prostate, or prostatic enlargement. When it is done, it may be done as open surgery or as laparoscopic (keyhole) surgery. These are done under general anaesthetic. Usually the procedure for cancer is a radical prostatectomy, which means that the seminal vesicles are removed and vas deferens is also tied off. Part of the prostate can also be removed from within the urethra, called transurethral resection of the prostate (TURP). Open surgery may involve a cut that is made in the perineum, or via an approach that involves a cut down the midline from the belly button to the pubic bone. Open surgery may be preferred if there is a suspicion that lymph nodes are involved and they need to be removed or biopsied during a procedure. A perineal approach will not involve lymph node removal and may result in less pain and a faster recovery following an operation. A TURP procedure uses a tube inserted into the urethra via the penis and some form of heat, electricity or laser to remove prostate tissue.


title: Prostate

text: The whole prostate can be removed. Complications that might develop because of surgery include urinary incontinence and erectile dysfunction because of damage to nerves during the operation, particularly if a cancer is very close to nerves. Ejaculation of semen will not occur during orgasm if the vas deferens are tied off and seminal vesicles removed, such as during a radial prosatectomy. This will mean a man becomes infertile. Sometimes, orgasm may not be able to occur or may be painful. The penis length may change if the part of the urethra within the prostate is also removed. General complications due to surgery can also develop, such as infections, bleeding, inadvertent damage to nearby organs or within the abdomen, and the formation of blood clots.


title: Prostate

text: The prostate was first formally identified by Venetian anatomist Niccolò Massa in "Anatomiae libri introductorius" (Introduction to Anatomy) 1536 and illustrated by Flemish anatomist Andreas Vesalius in "Tabulae anatomicae sex" (six anatomical tables) in 1538. Massa described it as a "glandular flesh upon which rests the neck of the bladder," and Vesalius as a "glandular body". The first time a word similar to 'prostate' was used to describe the gland is credited to André du Laurens in 1600, who described it as a term already in use by anatomists at the time. The term was however used at least as early as 1549 by French surgeon Ambroise Pare.


title: Prostate

text: At the time, Du Laurens was describing what was considered to be a pair of organs (not the single two-lobed organ), and the Latin term "prostatae" that was used was a mistranslation of the term for the Ancient Greek word used to describe the seminal vesicles, "parastatai"; although it has been argued that surgeons in Ancient Greece and Rome must have at least seen the prostate as an anatomical entity. The term "prostatae" was taken rather than the grammatically correct "prostator" (singular) and "prostatores" (plural) because the gender of the Ancient Greek term was taken as female, when it was in fact male.


title: Prostate

text: The fact that the prostate was one and not two organs was an idea popularised throughout the early 18th century, as was the English language term used to describe the organ, "prostate", attributed to William Cheselden. A monograph, "Practical observations on the treatment of the diseases of the prostate gland" by Everard Home in 1811, was important in the history of the prostate by describing and naming anatomical parts of the prostate, including the median lobe. The idea of the five lobes of the prostate was popularized following anatomical studies conducted by American urologist Oswald Lowsley in 1912. John E. McNeal first proposed the idea of "zones" in 1968; McNeal found that the relatively homogeneous cut surface of an adult prostate in no way resembled "lobes" and thus led to the description of "zones".


title: Prostate

text: Prostate cancer was first described in a speech to the Medical and Chiurgical Society of London in 1853 by surgeon John Adams and increasingly described by the late 19th century. Prostate cancer was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments of prostate cancer were surgeries to relieve urinary obstruction. Samuel David Gross has been credited with the first mention of a prostatectomy, as "too absurd to be seriously entertained" The first removal for prostate cancer (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital; partial removal of the gland was conducted by Theodore Billroth in 1867.


title: Prostate

text: Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh. In 1941, Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical castration" won Huggins the 1966 Nobel Prize in Physiology or Medicine.


title: Prostate

text: The role of the gonadotropin-releasing hormone (GnRH) in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who both won the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as leuprorelin and goserelin, were subsequently developed and used to treat prostate cancer. Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants. External beam radiotherapy became more popular as stronger X-ray radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds (for prostate cancer) was first described in 1983. Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by multiple regimens using a host of other systemic chemotherapy drugs.


title: Prostate

text: The prostate is found only in mammals. The prostate glands of male marsupials are proportionally larger than those of placental mammals. The presence of a functional prostate in monotremes is controversial, and if monotremes do possess functional prostates, they may not make the same contribution to semen as in other mammals.


title: Prostate

text: The structure of the prostate varies, ranging from tubuloalveolar (as in humans) to branched tubular. The gland is particularly well developed in dogs, foxes and boars, though in other mammals, such as bulls, it can be small and inconspicuous. In other animals, such as marsupials and small ruminants, the prostate is disseminate, meaning not specifically localisable as a distinct tissue, but present throughout the relevant part of the urethra; in other animals, such as red deer and American elk, it may be present as a specific organ and in a disseminate form. In some marsupial species, the size of the prostate gland changes seasonally. The prostate is the only accessory gland that occurs in male dogs. Dogs can produce in one hour as much prostatic fluid as a human can in a day. They excrete this fluid along with their urine to mark their territory. Additionally, dogs are the only species apart from humans seen to have a significant incidence of prostate cancer. In cetaceans (whales, dolphins, porpoises) the prostate is composed of diffuse urethral glands and is surrounded by a very powerful compressor muscle.


title: Prostate

text: The prostate gland originates with tissues in the urethral wall. This means the urethra, a compressible tube used for urination, runs through the middle of the prostate. This leads to an evolutionary design fault for some mammals, including human males. The prostate is prone to infection and enlargement later in life, constricting the urethra so urinating becomes slow and painful.


title: Prostate

text: Prostatic secretions vary among species. They are generally composed of simple sugars and are often slightly alkaline.


title: Prostate

text: Because the Skene's gland and the male prostate act similarly by secreting prostate-specific antigen (PSA), which is an ejaculate protein produced in males, and of prostate-specific acid phosphatase, the Skene's gland is sometimes referred to as the "female prostate". Although it is homologous to the male prostate (developed from the same embryological tissues), various aspects of its development in relation to the male prostate are widely unknown and a matter of research.


title: Morphine

text: Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ("Papaver somniferum"). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. There are numerous methods used to administer morphine: oral; sublingual; via inhalation; injection into a muscle; by injection under the skin; intravenously; injection into the space around the spinal cord; transdermal; or via rectal suppository. It acts directly on the central nervous system (CNS) to induce analgesia and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration. It can be taken for both acute pain and chronic pain and is frequently used for pain from myocardial infarction, kidney stones, and during labor. Its maximum effect is reached after about 20 minutes when administered intravenously and 60 minutes when administered by mouth, while the duration of its effect is 3–7 hours. Long-acting formulations of morphine are available as MS-Contin, Kadian, and other brand names as well as generically.


title: Morphine

text: Potentially serious side effects of morphine include decreased respiratory effort, vomiting, nausea, and low blood pressure. Morphine is addictive and prone to abuse. If one's dose is reduced after long-term use, opioid withdrawal symptoms may occur. Common side effects of morphine include drowsiness, vomiting, and constipation. Caution is advised for use of morphine during pregnancy or breast feeding, as it may affect the health of the baby.


title: Morphine

text: Morphine was first isolated between 1803 and 1805 by German pharmacist Friedrich Sertürner. This is generally believed to be the first isolation of an active ingredient from a plant. Merck began marketing it commercially in 1827. Morphine was more widely used after the invention of the hypodermic syringe in 18531855. Sertürner originally named the substance "morphium", after the Greek god of dreams, Morpheus, as it has a tendency to cause sleep.


title: Morphine

text: The primary source of morphine is isolation from poppy straw of the opium poppy. In 2013, approximately 523 tons of morphine were produced. Approximately 45 tons were used directly for pain, an increase of 400% over the last twenty years. Most use for this purpose was in the developed world. About 70 percent of morphine is used to make other opioids such as hydromorphone, oxymorphone, and heroin. It is a Schedule II drug in the United States, Class A in the United Kingdom, and Schedule I in Canada. It is on the World Health Organization's List of Essential Medicines. Morphine is sold under many brand names. In 2020, it was the 140th most commonly prescribed medication in the United States, with more than 4million prescriptions.


title: Morphine

text: Morphine is used primarily to treat both acute and chronic severe pain. Its duration of analgesia is about three to seven hours. Side-effects of nausea and constipation are rarely severe enough to warrant stopping treatment.


title: Morphine

text: It is used for pain due to myocardial infarction and for labor pains. However, concerns exist that morphine may increase mortality in the event of non ST elevation myocardial infarction.


title: Morphine

text: Morphine has also traditionally been used in the treatment of acute pulmonary edema. However, a 2006 review found little evidence to support this practice.


title: Morphine

text: Morphine is beneficial in reducing the symptom of shortness of breath due to both cancer and noncancer causes. In the setting of breathlessness at rest or on minimal exertion from conditions such as advanced cancer or end-stage cardiorespiratory diseases, regular, low-dose sustained-release morphine significantly reduces breathlessness safely, with its benefits maintained over time.


title: Morphine

text: Morphine is also available as a slow-release formulation for opiate substitution therapy (OST) in Austria, Germany, Bulgaria, Slovenia, and Canada for persons with opioid addiction who cannot tolerate either methadone or buprenorphine.


title: Morphine

text: Like loperamide and other opioids, morphine acts on the myenteric plexus in the intestinal tract, reducing gut motility, causing constipation. The gastrointestinal effects of morphine are mediated primarily by μ-opioid receptors in the bowel. By inhibiting gastric emptying and reducing propulsive peristalsis of the intestine, morphine decreases the rate of intestinal transit. Reduction in gut secretion and increased intestinal fluid absorption also contribute to the constipating effect. Opioids also may act on the gut indirectly through tonic gut spasms after inhibition of nitric oxide generation. This effect was shown in animals when a nitric oxide precursor, L-arginine, reversed morphine-induced changes in gut motility.


title: Morphine

text: Clinical studies consistently conclude that morphine, like other opioids, often causes hypogonadism and hormone imbalances in chronic users of both sexes. This side effect is dose-dependent and occurs in both therapeutic and recreational users. Morphine can interfere with menstruation in women by suppressing levels of luteinizing hormone. Many studies suggest the majority (perhaps as many as 90%) of chronic opioid users have opioid-induced hypogonadism. This effect may cause the increased likelihood of osteoporosis and bone fracture observed in chronic morphine users. Studies suggest the effect is temporary. , the effect of low-dose or acute use of morphine on the endocrine system is unclear.


title: Morphine

text: Most reviews conclude that opioids produce minimal impairment of human performance on tests of sensory, motor, or attentional abilities. However, recent studies have been able to show some impairments caused by morphine, which is not surprising, given that morphine is a central nervous system depressant. Morphine has resulted in impaired functioning on critical flicker frequency (a measure of overall CNS arousal) and impaired performance on the Maddox wing test (a measure of the deviation of the visual axes of the eyes). Few studies have investigated the effects of morphine on motor abilities; a high dose of morphine can impair finger tapping and the ability to maintain a low constant level of isometric force (i.e. fine motor control is impaired), though no studies have shown a correlation between morphine and gross motor abilities.


title: Morphine

text: In terms of cognitive abilities, one study has shown that morphine may have a negative impact on anterograde and retrograde memory, but these effects are minimal and transient. Overall, it seems that acute doses of opioids in non-tolerant subjects produce minor effects in some sensory and motor abilities, and perhaps also in attention and cognition. It is likely that the effects of morphine will be more pronounced in opioid-naive subjects than chronic opioid users.


title: Morphine

text: In chronic opioid users, such as those on Chronic Opioid Analgesic Therapy (COAT) for managing severe, chronic pain, behavioural testing has shown normal functioning on perception, cognition, coordination and behaviour in most cases. One 2000 study analysed COAT patients to determine whether they were able to safely operate a motor vehicle. The findings from this study suggest that stable opioid use does not significantly impair abilities inherent in driving (this includes physical, cognitive and perceptual skills). COAT patients showed rapid completion of tasks that require the speed of responding for successful performance (e.g., Rey Complex Figure Test) but made more errors than controls. COAT patients showed no deficits in visual-spatial perception and organization (as shown in the WAIS-R Block Design Test) but did show impaired immediate and short-term visual memory (as shown on the Rey Complex Figure Test – Recall). These patients showed no impairments in higher-order cognitive abilities (i.e., planning). COAT patients appeared to have difficulty following instructions and showed a propensity toward impulsive behaviour, yet this did not reach statistical significance. It is important to note that this study reveals that COAT patients have no domain-specific deficits, which supports the notion that chronic opioid use has minor effects on psychomotor, cognitive, or neuropsychological functioning.


title: Morphine

text: Morphine is a highly addictive substance. In controlled studies comparing the physiological and subjective effects of heroin and morphine in individuals formerly addicted to opiates, subjects showed no preference for one drug over the other. Equipotent, injected doses had comparable action courses, with no difference in subjects' self-rated feelings of euphoria, ambition, nervousness, relaxation, drowsiness, or sleepiness. Short-term addiction studies by the same researchers demonstrated that tolerance developed at a similar rate to both heroin and morphine. When compared to the opioids hydromorphone, fentanyl, oxycodone, and pethidine/meperidine, former addicts showed a strong preference for heroin and morphine, suggesting that heroin and morphine are particularly susceptible to abuse and addiction. Morphine and heroin were also much more likely to produce euphoria and other positive subjective effects when compared to these other opioids. The choice of heroin and morphine over other opioids by former drug addicts may also be because heroin (also known as morphine diacetate, diamorphine, or diacetyl morphine) is an ester of morphine and a morphine prodrug, essentially meaning they are identical drugs "in vivo". Heroin is converted to morphine before binding to the opioid receptors in the brain and spinal cord, where morphine causes the subjective effects, which is what the addicted individuals are seeking.


title: Morphine

text: Several hypotheses are given about how tolerance develops, including opioid receptor phosphorylation (which would change the receptor conformation), functional decoupling of receptors from G-proteins (leading to receptor desensitization), μ-opioid receptor internalization or receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the cAMP pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt.) CCK might mediate some counter-regulatory pathways responsible for opioid tolerance. CCK-antagonist drugs, specifically proglumide, have been shown to slow the development of tolerance to morphine.


title: Morphine

text: Cessation of dosing with morphine creates the prototypical opioid withdrawal syndrome, which, unlike that of barbiturates, benzodiazepines, alcohol, or sedative-hypnotics, is not fatal by itself in otherwise healthy people.


title: Morphine

text: Acute morphine withdrawal, along with that of any other opioid, proceeds through a number of stages. Other opioids differ in the intensity and length of each, and weak opioids and mixed agonist-antagonists may have acute withdrawal syndromes that do not reach the highest level. As commonly cited, they are:


title: Morphine

text: In advanced stages of withdrawal, ultrasonographic evidence of pancreatitis has been demonstrated in some patients and is presumably attributed to spasm of the pancreatic sphincter of Oddi.


title: Morphine

text: The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next scheduled dose, sometimes within as early as a few hours (usually 6 h to 12 h) after the last administration. Early symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria, sweating, and in some cases a strong drug craving. Severe headache, restlessness, irritability, loss of appetite, body aches, severe abdominal pain, nausea and vomiting, tremors, and even stronger and more intense drug craving appear as the syndrome progresses. Severe depression and vomiting are very common. During the acute withdrawal period, systolic and diastolic blood pressures increase, usually beyond premorphine levels, and heart rate increases, which have potential to cause a heart attack, blood clot, or stroke.


title: Morphine

text: Chills or cold flashes with goose bumps ("cold turkey") alternating with flushing (hot flashes), kicking movements of the legs ("kicking the habit") and excessive sweating are also characteristic symptoms. Severe pains in the bones and muscles of the back and extremities occur, as do muscle spasms. At any point during this process, a suitable narcotic can be administered that will dramatically reverse the withdrawal symptoms. Major withdrawal symptoms peak between 48 h and 96 h after the last dose and subside after about 8 to 12 days. Sudden withdrawal by heavily dependent users who are in poor health is very rarely fatal. Morphine withdrawal is considered less dangerous than alcohol, barbiturate, or benzodiazepine withdrawal.


title: Morphine

text: The psychological dependence associated with morphine addiction is complex and protracted. Long after the physical need for morphine has passed, the addict will usually continue to think and talk about the use of morphine (or other drugs) and feel strange or overwhelmed coping with daily activities without being under the influence of morphine. Psychological withdrawal from morphine is usually a very long and painful process. Addicts often experience severe depression, anxiety, insomnia, mood swings, amnesia (forgetfulness), low self-esteem, confusion, paranoia, and other psychological disorders. Without intervention, the syndrome will run its course, and most of the overt physical symptoms will disappear within 7 to 10 days including psychological dependence. A high probability of relapse exists after morphine withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. Testimony to morphine's addictive and reinforcing nature is its relapse rate. Abusers of morphine (and heroin) have one of the highest relapse rates among all drug users, ranging up to 98% in the estimation of some medical experts.


title: Morphine

text: A large overdose can cause asphyxia and death by respiratory depression if the person does not receive medical attention immediately. Overdose treatment includes the administration of naloxone. The latter completely reverses morphine's effects, but may result in immediate onset of withdrawal in opiate-addicted subjects. Multiple doses may be needed as the duration of action of morphine is longer than that of naloxone.


title: Morphine

text: The LD for humans of morphine sulphate and other preparations is not known with certainty. One poor quality study on morphine overdoses among soldiers reported that the fatal dose was 0.78 mcg/ml in males (~71 mg for an average 90 kg adult man) and 0.98mcg/ml in females (~74 mg for an average 75 kg female). It was not specified whether the dose was oral, parenteral or IV. Laboratory animal studies are usually cited in the literature. In serious drug dependency (high tolerance), 2000–3000 mg per day can be tolerated.


title: Morphine

text: Morphine is the prototypical opioid and is the standard agonist to which other opioids are tested. It interacts predominantly with the μ–δ-opioid (Mu-Delta) receptor heteromer. The μ-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve.


title: Morphine

text: Morphine is a phenanthrene opioid receptor agonist – its main effect is binding to and activating the μ-opioid receptor (MOR) in the central nervous system. Its intrinsic activity at the MOR is heavily dependent on the assay and tissue being tested; in some situations it is a full agonist while in others it can be a partial agonist or even antagonist. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Activation of the MOR is associated with analgesia, sedation, euphoria, physical dependence, and respiratory depression. Morphine is also a κ-opioid receptor (KOR) and δ-opioid receptor (DOR) agonist. Activation of the KOR is associated with spinal analgesia, miosis (pinpoint pupils), and psychotomimetic effects. The DOR is thought to play a role in analgesia. Although morphine does not bind to the σ receptor, it has been shown that σ receptor agonists, such as (+)-pentazocine, inhibit morphine analgesia, and σ receptor antagonists enhance morphine analgesia, suggesting downstream involvement of the σ receptor in the actions of morphine.


title: Morphine

text: The effects of morphine can be countered with opioid receptor antagonists such as naloxone and naltrexone; the development of tolerance to morphine may be inhibited by NMDA receptor antagonists such as ketamine, dextromethorphan, and memantine. The rotation of morphine with chemically dissimilar opioids in the long-term treatment of pain will slow down the growth of tolerance in the longer run, particularly agents known to have significantly incomplete cross-tolerance with morphine such as levorphanol, ketobemidone, piritramide, and methadone and its derivatives; all of these drugs also have NMDA antagonist properties. It is believed that the strong opioid with the most incomplete cross-tolerance with morphine is either methadone or dextromoramide.


title: Morphine

text: Studies have shown that morphine can alter the expression of a number of genes. A single injection of morphine has been shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins.


title: Morphine

text: Morphine has long been known to act on receptors expressed on cells of the central nervous system resulting in pain relief and analgesia. In the 1970s and '80s, evidence suggesting that opioid drug addicts show increased risk of infection (such as increased pneumonia, tuberculosis, and HIV/AIDS) led scientists to believe that morphine may also affect the immune system. This possibility increased interest in the effect of chronic morphine use on the immune system.


title: Morphine

text: The first step of determining that morphine may affect the immune system was to establish that the opiate receptors known to be expressed on cells of the central nervous system are also expressed on cells of the immune system. One study successfully showed that dendritic cells, part of the innate immune system, display opiate receptors. Dendritic cells are responsible for producing cytokines, which are the tools for communication in the immune system. This same study showed that dendritic cells chronically treated with morphine during their differentiation produce more interleukin-12 (IL-12), a cytokine responsible for promoting the proliferation, growth, and differentiation of T-cells (another cell of the adaptive immune system) and less interleukin-10 (IL-10), a cytokine responsible for promoting a B-cell immune response (B cells produce antibodies to fight off infection).


title: Morphine

text: This regulation of cytokines appear to occur via the p38 MAPKs (mitogen-activated protein kinase)-dependent pathway. Usually, the p38 within the dendritic cell expresses TLR 4 (toll-like receptor 4), which is activated through the ligand LPS (lipopolysaccharide). This causes the p38 MAPK to be phosphorylated. This phosphorylation activates the p38 MAPK to begin producing IL-10 and IL-12. When the dendritic cells are chronically exposed to morphine during their differentiation process then treated with LPS, the production of cytokines is different. Once treated with morphine, the p38 MAPK does not produce IL-10, instead favoring production of IL-12. The exact mechanism through which the production of one cytokine is increased in favor over another is not known. Most likely, the morphine causes increased phosphorylation of the p38 MAPK. Transcriptional level interactions between IL-10 and IL-12 may further increase the production of IL-12 once IL-10 is not being produced. This increased production of IL-12 causes increased T-cell immune response.


title: Morphine

text: Further studies on the effects of morphine on the immune system have shown that morphine influences the production of neutrophils and other cytokines. Since cytokines are produced as part of the immediate immunological response (inflammation), it has been suggested that they may also influence pain. In this way, cytokines may be a logical target for analgesic development. Recently, one study has used an animal model (hind-paw incision) to observe the effects of morphine administration on the acute immunological response. Following hind-paw incision, pain thresholds and cytokine production were measured. Normally, cytokine production in and around the wounded area increases in order to fight infection and control healing (and, possibly, to control pain), but pre-incisional morphine administration (0.1 mg/kg to 10.0 mg/kg) reduced the number of cytokines found around the wound in a dose-dependent manner. The authors suggest that morphine administration in the acute post-injury period may reduce resistance to infection and may impair the healing of the wound.


title: Morphine

text: Morphine can be taken orally, sublingually, bucally, rectally, subcutaneously, intranasally, intravenously, intrathecally or epidurally and inhaled via a nebulizer. As a recreational drug, it is becoming more common to inhale ("Chasing the Dragon"), but, for medical purposes, intravenous (IV) injection is the most common method of administration. Morphine is subject to extensive first-pass metabolism (a large proportion is broken down in the liver), so, if taken orally, only 40% to 50% of the dose reaches the central nervous system. Resultant plasma levels after subcutaneous (SC), intramuscular (IM), and IV injection are all comparable. After IM or SC injections, morphine plasma levels peak in approximately 20 min, and, after oral administration, levels peak in approximately 30 min. Morphine is metabolised primarily in the liver and approximately 87% of a dose of morphine is excreted in the urine within 72 h of administration. Morphine is metabolized primarily into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 (UGT2B7). About 60% of morphine is converted to M3G, and 6% to 10% is converted to M6G. Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys. M3G does not undergo opioid receptor binding and has no analgesic effect. M6G binds to μ-receptors and is half as potent an analgesic as morphine in humans. Morphine may also be metabolized into small amounts of normorphine, codeine, and hydromorphone. Metabolism rate is determined by gender, age, diet, genetic makeup, disease state (if any), and use of other medications. The elimination half-life of morphine is approximately 120 min, though there may be slight differences between men and women. Morphine can be stored in fat, and, thus, can be detectable even after death. Morphine can cross the blood–brain barrier, but, because of poor lipid solubility, protein binding, rapid conjugation with glucuronic acid and ionization, it does not cross easily. Heroin, which is derived from morphine, crosses the blood–brain barrier more easily, making it more potent.


title: Morphine

text: There are extended-release formulations of orally administered morphine whose effect last longer, which can be given once per day. Brand names for this formulation of morphine include Avinza, Kadian, MS Contin and Dolcontin. For constant pain, the relieving effect of extended-release morphine given once (for Kadian) or twice (for MS Contin) every 24 hours is roughly the same as multiple administrations of "immediate release" (or "regular") morphine. Extended-release morphine can be administered together with "rescue doses" of immediate-release morphine as needed in case of breakthrough pain, each generally consisting of 5% to 15% of the 24-hour extended-release dosage.


title: Morphine

text: Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, can be detected in blood, plasma, hair, and urine using an immunoassay. Chromatography can be used to test for each of these substances individually. Some testing procedures hydrolyze metabolic products into morphine before the immunoassay, which must be considered when comparing morphine levels in separately published results. Morphine can also be isolated from whole blood samples by solid phase extraction (SPE) and detected using liquid chromatography-mass spectrometry (LC-MS).


title: Morphine

text: A 1999 review estimated that relatively low doses of heroin (which metabolizes immediately into morphine) are detectable by standard urine tests for 1–1.5 days after use. A 2009 review determined that, when the analyte is morphine and the limit of detection is 1ng/ml, a 20mg intravenous (IV) dose of morphine is detectable for 12–24 hours. A limit of detection of 0.6ng/ml had similar results.


title: Morphine

text: Morphine has a highly challenging chemical structure. It is a pentacyclic 3°amine (alkaloid) with 5 stereogenic centers and exists in 32 stereoisomeric forms. But the desired analgesic activity resides exclusively in the natural product, the (-)-enantiomer with the configuration (5R,6S,9R,13S,14R).


title: Morphine

text: Morphine is the most abundant opiate found in opium, the dried latex extracted by shallowly scoring the unripe seedpods of the "Papaver somniferum" poppy. Morphine is generally 8–14% of the dry weight of opium, although specially bred cultivars reach 26% or produce little morphine at all (under 1%, perhaps down to 0.04%). The latter varieties, including the 'Przemko' and 'Norman' cultivars of the opium poppy, are used to produce two other alkaloids, thebaine and oripavine, which are used in the manufacture of semi-synthetic and synthetic opioids like oxycodone and etorphine and some other types of drugs. "P. bracteatum" does not contain morphine or codeine, or other narcotic phenanthrene-type, alkaloids. This species is rather a source of thebaine. Occurrence of morphine in other Papaverales and Papaveraceae, as well as in some species of hops and mulberry trees has not been confirmed. Morphine is produced most predominantly early in the life cycle of the plant. Past the optimum point for extraction, various processes in the plant produce codeine, thebaine, and in some cases negligible amounts of hydromorphone, dihydromorphine, dihydrocodeine, tetrahydro-thebaine, and hydrocodone (these compounds are rather synthesized from thebaine and oripavine).


title: Morphine

text: In the brain of mammals, morphine is detectable in trace steady-state concentrations. The human body also produces endorphins, which are chemically related endogenous opioid peptides that function as neuropeptides and have similar effects to morphine.


title: Morphine

text: Morphine is an endogenous opioid in humans. Various human cells are capable of synthesizing and releasing it, including white blood cells. The primary biosynthetic pathway for morphine in humans consists of:


title: Morphine

text: The intermediate ("S")-norlaudanosoline (also known as tetrahydropapaveroline) is synthesized through addition of DOPAL and dopamine. CYP2D6, a cytochrome P450 isoenzymem is involved in two steps along the biosynthetic pathway, catalyzing both the biosynthesis of dopamine from tyramine and of morphine from codeine.


title: Morphine

text: Urinary concentrations of endogenous codeine and morphine have been found to significantly increase in individuals taking L-DOPA for the treatment of Parkinson's disease.


title: Morphine

text: Morphine is biosynthesized in the opium poppy from the tetrahydroisoquinoline reticuline. It is converted into salutaridine, thebaine, and oripavine. The enzymes involved in this process are the salutaridine synthase, salutaridine:NADPH 7-oxidoreductase and the codeinone reductase. Researchers are attempting to reproduce the biosynthetic pathway that produces morphine in genetically engineered yeast. In June 2015 the "S"-reticuline could be produced from sugar and "R"-reticuline could be converted to morphine, but the intermediate reaction could not be performed. In August 2015 the first complete synthesis of thebaine and hydrocodone in yeast were reported, but the process would need to be 100,000 times more productive to be suitable for commercial use.


title: Morphine

text: Elements of the morphine structure have been used to create completely synthetic drugs such as the morphinan family (levorphanol, dextromethorphan and others) and other groups that have many members with morphine-like qualities. The modification of morphine and the aforementioned synthetics has also given rise to non-narcotic drugs with other uses such as emetics, stimulants, antitussives, anticholinergics, muscle relaxants, local anaesthetics, general anaesthetics, and others. Morphine-derived agonist–antagonist drugs have also been developed.


title: Morphine

text: Morphine is a benzylisoquinoline alkaloid with two additional ring closures. As Jack DeRuiter of the Department of Drug Discovery and Development (formerly, Pharmacal Sciences), Harrison School of Pharmacy, Auburn University stated in his Fall 2000 course notes for that earlier department's "Principles of Drug Action 2" course, "Examination of the morphine molecule reveals the following structural features important to its pharmacological profile...


title: Morphine

text: Morphine and most of its derivatives do not exhibit optical isomerism, although some more distant relatives like the morphinan series (levorphanol, dextorphan and the racemic parent chemical racemorphan) do, and as noted above stereoselectivity in vivo is an important issue.


title: Morphine

text: Most of the licit morphine produced is used to make codeine by methylation. It is also a precursor for many drugs including heroin (3,6-diacetylmorphine), hydromorphone (dihydromorphinone), and oxymorphone (14-hydroxydihydromorphinone). Most semi-synthetic opioids, both of the morphine and codeine subgroups, are created by modifying one or more of the following:


title: Morphine

text: Many morphine derivatives can also be manufactured using thebaine or codeine as a starting material. Replacement of the "N"-methyl group of morphine with an "N"-phenylethyl group results in a product that is 18 times more powerful than morphine in its opiate agonist potency. Combining this modification with the replacement of the 6-hydroxyl with a 6-methylene group produces a compound some 1,443 times more potent than morphine, stronger than the Bentley compounds such as etorphine (M99, the Immobilon tranquilliser dart) by some measures. Closely related to morphine are the opioids morphine-"N"-oxide (genomorphine), which is a pharmaceutical that is no longer in common use; and pseudomorphine, an alkaloid that exists in opium, form as degradation products of morphine.


title: Morphine

text: As a result of the extensive study and use of this molecule, more than 250 morphine derivatives (also counting codeine and related drugs) have been developed since the last quarter of the 19th century. These drugs range from 25% the analgesic strength of codeine (or slightly more than 2% of the strength of morphine) to several thousand times the strength of morphine, to powerful opioid antagonists, including naloxone (Narcan), naltrexone (Trexan), diprenorphine (M5050, the reversing agent for the Immobilon dart) and nalorphine (Nalline). Some opioid agonist-antagonists, partial agonists, and inverse agonists are also derived from morphine. The receptor-activation profile of the semi-synthetic morphine derivatives varies widely and some, like apomorphine are devoid of narcotic effects.


title: Morphine

text: Both morphine and its hydrated form are sparingly soluble in water. For this reason, pharmaceutical companies produce sulfate and hydrochloride salts of the drug, both of which are over 300 times more water-soluble than their parent molecule. Whereas the pH of a saturated morphine hydrate solution is 8.5, the salts are acidic. Since they derive from a strong acid but weak base, they are both at about pH = 5; as a consequence, the morphine salts are mixed with small amounts of NaOH to make them suitable for injection.


title: Morphine

text: A number of salts of morphine are used, with the most common in current clinical use being the hydrochloride, sulfate, tartrate, and citrate; less commonly methobromide, hydrobromide, hydroiodide, lactate, chloride, and bitartrate and the others listed below. Morphine diacetate (heroin) is not a salt, but rather a further derivative, see above.


title: Morphine

text: Morphine meconate is a major form of the alkaloid in the poppy, as is morphine pectinate, nitrate, sulfate, and some others. Like codeine, dihydrocodeine and other (especially older) opiates, morphine has been used as the salicylate salt by some suppliers and can be easily compounded, imparting the therapeutic advantage of both the opioid and the NSAID; multiple barbiturate salts of morphine were also used in the past, as was/is morphine valerate, the salt of the acid being the active principle of valerian. Calcium morphenate is the intermediate in various latex and poppy-straw methods of morphine production, more rarely sodium morphenate takes its place. Morphine ascorbate and other salts such as the tannate, citrate, and acetate, phosphate, valerate and others may be present in poppy tea depending on the method of preparation.


title: Morphine

text: The salts listed by the United States Drug Enforcement Administration for reporting purposes, in addition to a few others, are as follows:


title: Morphine

text: In the opium poppy, the alkaloids are bound to meconic acid. The method is to extract from the crushed plant with diluted sulfuric acid, which is a stronger acid than meconic acid, but not so strong to react with alkaloid molecules. The extraction is performed in many steps (one amount of crushed plant is extracted at least six to ten times, so practically every alkaloid goes into the solution). From the solution obtained at the last extraction step, the alkaloids are precipitated by either ammonium hydroxide or sodium carbonate. The last step is purifying and separating morphine from other opium alkaloids. The somewhat similar Gregory process was developed in the United Kingdom during the Second World War, which begins with stewing the entire plant, in most cases save the roots and leaves, in plain or mildly acidified water, then proceeding through steps of concentration, extraction, and purification of alkaloids. Other methods of processing "poppy straw" (i.e., dried pods and stalks) use steam, one or more of several types of alcohol, or other organic solvents.


title: Morphine

text: The poppy straw methods predominate in Continental Europe and the British Commonwealth, with the latex method in most common use in India. The latex method can involve either vertical or horizontal slicing of the unripe pods with a two-to five-bladed knife with a guard developed specifically for this purpose to the depth of a fraction of a millimetre and scoring of the pods can be done up to five times. An alternative latex method sometimes used in China in the past is to cut off the poppy heads, run a large needle through them, and collect the dried latex 24 to 48 hours later.


title: Morphine

text: In India, opium harvested by licensed poppy farmers is dehydrated to uniform levels of hydration at government processing centers, and then sold to pharmaceutical companies that extract morphine from the opium. However, in Turkey and Tasmania, morphine is obtained by harvesting and processing the fully mature dry seed pods with attached stalks, called "poppy straw". In Turkey, a water extraction process is used, while in Tasmania, a solvent extraction process is used.


title: Morphine

text: Opium poppy contains at least 50 different alkaloids, but most of them are of very low concentration. Morphine is the principal alkaloid in raw opium and constitutes roughly 8–19% of opium by dry weight (depending on growing conditions). Some purpose-developed strains of poppy now produce opium that is up to 26% morphine by weight. A rough rule of thumb to determine the morphine content of pulverised dried poppy straw is to divide the percentage expected for the strain or crop via the latex method by eight or an empirically determined factor, which is often in the range of 5 to 15. The Norman strain of "P. Somniferum", also developed in Tasmania, produces down to 0.04% morphine but with much higher amounts of thebaine and oripavine, which can be used to synthesise semi-synthetic opioids as well as other drugs like stimulants, emetics, opioid antagonists, anticholinergics, and smooth-muscle agents.


title: Morphine

text: In the 1950s and 1960s, Hungary supplied nearly 60% of Europe's total medication-purpose morphine production. To this day, poppy farming is legal in Hungary, but poppy farms are limited by law to . It is also legal to sell dried poppy in flower shops for use in floral arrangements.


title: Morphine

text: It was announced in 1973 that a team at the National Institutes of Health in the United States had developed a method for total synthesis of morphine, codeine, and thebaine using coal tar as a starting material. A shortage in codeine-hydrocodone class cough suppressants (all of which can be made from morphine in one or more steps, as well as from codeine or thebaine) was the initial reason for the research.


title: Morphine

text: Most morphine produced for pharmaceutical use around the world is actually converted into codeine as the concentration of the latter in both raw opium and poppy straw is much lower than that of morphine; in most countries, the usage of codeine (both as end-product and precursor) is at least equal or greater than that of morphine on a weight basis.


title: Morphine

text: The first morphine total synthesis, devised by Marshall D. Gates, Jr. in 1952, remains a widely used example of total synthesis. Several other syntheses were reported, notably by the research groups of Rice, Evans, Fuchs, Parker, Overman, Mulzer-Trauner, White, Taber, Trost, Fukuyama, Guillou, and Stork. Because of the stereochemical complexity and consequent synthetic challenge presented by this polycyclic structure, Michael Freemantle has expressed the view that it is "highly unlikely" that a chemical synthesis will ever be cost-effective such that it could compete with the cost of producing morphine from the opium poppy.


title: Morphine

text: Morphine is a precursor in the manufacture in a number of opioids such as dihydromorphine, hydromorphone, hydrocodone, and oxycodone as well as codeine, which itself has a large family of semi-synthetic derivatives.


title: Morphine

text: Illicit morphine is produced, though rarely, from codeine found in over-the-counter cough and pain medicines. Another illicit source is morphine extracted from extended-release morphine products. Chemical reactions can then be used to convert morphine, dihydromorphine, and hydrocodone into heroin or other opioids [e.g., diacetyldihydromorphine (Paralaudin), and thebacon]. Other clandestine conversions—of morphine, into ketones of the hydromorphone class, or other derivatives like dihydromorphine (Paramorfan), desomorphine (Permonid), metopon, etc., and of codeine into hydrocodone (Dicodid), dihydrocodeine (Paracodin), etc. —require greater expertise, and types and quantities of chemicals and equipment that are more difficult to source, and so are more rarely used, illicitly (but cases have been recorded).


title: Morphine

text: An opium-based elixir has been ascribed to alchemists of Byzantine times, but the specific formula was lost during the Ottoman conquest of Constantinople (Istanbul). Around 1522, Paracelsus made reference to an opium-based elixir that he called "laudanum" from the Latin word "laudāre", meaning "to praise" He described it as a potent painkiller, but recommended that it be used sparingly. The recipe given differs substantially from that of modern-day laudanum.


title: Morphine

text: Morphine was discovered as the first active alkaloid extracted from the opium poppy plant in December 1804 in Paderborn by German pharmacist Friedrich Sertürner. In 1817, Sertürner reported experiments in which he administered morphine to himself, three young boys, three dogs, and a mouse; all four people almost died. Sertürner originally named the substance "morphium" after the Greek god of dreams, Morpheus, as it has a tendency to cause sleep. Sertürner's morphium was six times stronger than opium. He hypothesized that, because lower doses of the drug were needed, it would be less addictive. However Sertürner became addicted to the drug, warning that "I consider it my duty to attract attention to the terrible effects of this new substance I called morphium in order that calamity may be averted."


title: Morphine

text: The drug was first marketed to the general public by Sertürner and Company in 1817 as a pain medication, and also as a treatment for opium and alcohol addiction. It was first used as a poison in 1822 when Dr. Edme Castaing of France was convicted of murdering a patient. Commercial production began in Darmstadt, Germany, in 1827 by the pharmacy that became the pharmaceutical company Merck, with morphine sales being a large part of their early growth. In the 1850s, Alexander Wood reported that he had injected morphine into his wife Rebecca as an experiment; the myth goes that this killed her because of respiratory depression, but she outlived her husband by ten years.


title: Morphine

text: Later it was found that morphine was more addictive than either alcohol or opium, and its extensive use during the American Civil War allegedly resulted in over 400,000 people with the "soldier's disease" of morphine addiction. This idea has been a subject of controversy, as there have been suggestions that such a disease was in fact a fabrication; the first documented use of the phrase "soldier's disease" was in 1915.


title: Morphine

text: Diacetylmorphine (better known as heroin) was synthesized from morphine in 1874 and brought to market by Bayer in 1898. Heroin is approximately 1.5 to 2 times more potent than morphine weight for weight. Due to the lipid solubility of diacetylmorphine, it can cross the blood–brain barrier faster than morphine, subsequently increasing the reinforcing component of addiction. Using a variety of subjective and objective measures, one study estimated the relative potency of heroin to morphine administered intravenously to post-addicts to be 1.80–2.66 mg of morphine sulfate to 1 mg of diamorphine hydrochloride (heroin).


title: Morphine

text: Morphine became a controlled substance in the US under the Harrison Narcotics Tax Act of 1914, and possession without a prescription in the US is a criminal offense.


title: Morphine

text: Morphine was the most commonly abused narcotic analgesic in the world until heroin was synthesized and came into use. In general, until the synthesis of dihydromorphine (), the dihydromorphinone class of opioids (1920s), and oxycodone (1916) and similar drugs, there were no other drugs in the same efficacy range as opium, morphine, and heroin, with synthetics still several years away (pethidine was invented in Germany in 1937) and opioid agonists among the semi-synthetics were analogues and derivatives of codeine such as dihydrocodeine (Paracodin), ethylmorphine (Dionine), and benzylmorphine (Peronine). Even today, morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce, all other things being equal; local conditions and user preference may cause hydromorphone, oxymorphone, high-dose oxycodone, or methadone as well as dextromoramide in specific instances such as 1970s Australia, to top that particular list. The stop-gap drugs used by the largest absolute number of heroin addicts is probably codeine, with significant use also of dihydrocodeine, poppy straw derivatives like poppy pod and poppy seed tea, propoxyphene, and tramadol.


title: Morphine

text: The structural formula of morphine was determined by 1925 by Robert Robinson. At least three methods of total synthesis of morphine from starting materials such as coal tar and petroleum distillates have been patented, the first of which was announced in 1952, by Dr. Marshall D. Gates, Jr. at the University of Rochester. Still, the vast majority of morphine is derived from the opium poppy by either the traditional method of gathering latex from the scored, unripe pods of the poppy, or processes using poppy straw, the dried pods and stems of the plant, the most widespread of which was invented in Hungary in 1925 and announced in 1930 by Hungarian pharmacologist János Kabay.


title: Morphine

text: In 2003, there was discovery of endogenous morphine occurring naturally in the human body. Thirty years of speculation were made on this subject because there was a receptor that, it appeared, reacted only to morphine: the μ-opioid receptor in human tissue. Human cells that form in reaction to cancerous neuroblastoma cells have been found to contain trace amounts of endogenous morphine.


title: Morphine

text: The euphoria, comprehensive alleviation of distress and therefore all aspects of suffering, promotion of sociability and empathy, "body high", and anxiolysis provided by narcotic drugs including the opioids can cause the use of high doses in the absence of pain for a protracted period, which can impart a morbid craving for the drug in the user. As the prototype of the entire opioid class of drugs, morphine has properties that may lead to its misuse. Morphine addiction is the model upon which the current perception of addiction is based.


title: Morphine

text: Animal and human studies and clinical experience back up the contention that morphine is one of the most euphoric drugs known, and via all but the IV route heroin and morphine cannot be distinguished according to studies because heroin is a prodrug for the delivery of systemic morphine. Chemical changes to the morphine molecule yield other euphorigenics such as dihydromorphine, hydromorphone (Dilaudid, Hydal), and oxymorphone (Numorphan, Opana), as well as the latter three's methylated equivalents dihydrocodeine, hydrocodone, and oxycodone, respectively; in addition to heroin, there are dipropanoylmorphine, diacetyldihydromorphine, and other members of the 3,6 morphine diester category like nicomorphine and other similar semi-synthetic opiates like desomorphine, hydromorphinol, etc. used clinically in many countries of the world but also produced illicitly in rare instances.


title: Morphine

text: In general, non-medical use of morphine entails taking more than prescribed or outside of medical supervision, injecting oral formulations, mixing it with unapproved potentiators such as alcohol, cocaine, and the like, or defeating the extended-release mechanism by chewing the tablets or turning into a powder for snorting or preparing injectables. The latter method can be as time-consuming and involved as traditional methods of smoking opium. This and the fact that the liver destroys a large percentage of the drug on the first pass impacts the demand side of the equation for clandestine re-sellers, as many customers are not needle users and may have been disappointed with ingesting the drug orally. As morphine is generally as hard or harder to divert than oxycodone in a lot of cases, morphine in any form is uncommon on the street, although ampoules and phials of morphine injection, pure pharmaceutical morphine powder, and soluble multi-purpose tablets are very popular where available.


title: Morphine

text: Morphine is also available in a paste that is used in the production of heroin, which can be smoked by itself or turned to a soluble salt and injected; the same goes for the penultimate products of the Kompot (Polish Heroin) and black tar processes. Poppy straw as well as opium can yield morphine of purity levels ranging from poppy tea to near-pharmaceutical-grade morphine by itself or with all of the more than 50 other alkaloids. It also is the active narcotic ingredient in opium and all of its forms, derivatives, and analogues as well as forming from breakdown of heroin and otherwise present in many batches of illicit heroin as the result of incomplete acetylation.


title: Morphine

text: Morphine is marketed under many different brand names in various parts of the world. It was formerly called Morphia in British English.


title: Morphine

text: Informal names for morphine include: Cube Juice, Dope, Dreamer, Emsel, First Line, God's Drug, Hard Stuff, Hocus, Hows, Lydia, Lydic, M, Miss Emma, Mister Blue, Monkey, Morf, Morph, Morphide, Morphie, Morpho, Mother, MS, Ms. Emma, Mud, New Jack Swing (if mixed with heroin), Sister, Tab, Unkie, Unkie White, and Stuff.


title: Morphine

text: MS Contin tablets are known as misties, and the 100 mg extended-release tablets as greys and blockbusters. The "speedball" can use morphine as the opioid component, which is combined with cocaine, amphetamines, methylphenidate, or similar drugs. "Blue Velvet" is a combination of morphine with the antihistamine tripelennamine (Pyrabenzamine, PBZ, Pelamine) taken by injection, or less commonly the mixture when swallowed or used as a retention enema; the name is also known to refer to a combination of tripelennamine and dihydrocodeine or codeine tablets or syrups taken by mouth. "Morphia" is an older official term for morphine also used as a slang term. "Driving Miss Emma" is intravenous administration of morphine. Multi-purpose tablets (readily soluble hypodermic tablets that can also be swallowed or dissolved under the tongue or betwixt the cheek and jaw) are known, as are some brands of hydromorphone, as Shake & Bake or Shake & Shoot.


title: Morphine

text: Morphine can be smoked, especially diacetylmorphine (heroin), the most common method being the "Chasing The Dragon" method. To perform acetylation to turn the morphine into heroin and related drugs immediately prior to use is known as AAing (for Acetic Anhydride) or home-bake, and the output of the procedure also known as home-bake or, Blue Heroin (not to be confused with Blue Magic heroin, or the linctus known as Blue Morphine or Blue Morphone, or the Blue Velvet mixture described above).