Or Sam Opiates & Opioids 04 19 2011

Opiates, Opioids A rose by any other name… Larry Lombard, BA History of Medicine, BPharm, CDP, NCAC II Quality Assurance Manager Serenity Lane April 19, 2011

Opium poppy – Papaver somniferum

1400 BCE Crete Poppy goddess The poppy heads are cut to extract the opium before the pods ripen in the same way as they are now

Paracelsus Born Philippus Aureolus Theophrastus Bombastus von Hohenheim , 11 November or 17 December 1493 – 24 September 1541 in was a Renaissance physician, botanist, alchemist, astrologer, and general occultist. "Paracelsus", meaning "equal to or greater than Celsus", refers to the Roman encyclopedist Aulus Cornelius Celsus from the 1st century known for his tract on medicine and is regarded as the first systematic botanist.

He is also credited for giving zinc its name, calling it zink ( zinkum) in about 1526, based on the sharp pointed appearance of its crystals after smelting and the old German word "zinke" for pointed. Paracelsus was also responsible for the creation of laudanum, an opium tincture very common until the 19th century.

Paracelsus Discovered that the alkaloids in opium are far more soluble in alcohol than water. Having experimented with various opium concoctions, Paracelsus came across a specific tincture of opium that was of considerable use in reducing pain. He called this preparation laudanum, derived from the Latin verb laudare, to praise.

Initially, the term "laudanum" referred to any combination of opium and alcohol. Paracelsus' laudanum was strikingly different from the standard laudanum of the 17th century and beyond. His preparation contained opium, crushed pearls, musk, amber, and other substances. One researcher has documented that "Laudanum, as listed in the London Pharmacoepoeia (1618), was a pill made from opium, saffron, castor, ambergris, musk and nutmeg."

While laudanum is known as a "whole opium" preparation since it historically contained all the opium alkaloids, today the drug is often processed to remove all or most of the noscapine (also known as narcotine) present as this is a strong emetic and does not add appreciably to the analgesic or anti-propulsive properties of opium; the resulting solution is called Denarcotized Tincture of Opium or Deodorized Tincture of Opium (DTO)

DTO is sometimes also erroneously employed to abbreviate " diluted tincture of opium", a 1:25 mixture of opium tincture to water prescribed to treat withdrawal symptoms in newborns whose mothers were using opiates while pregnant. DTO should never be used to Rx. It can killed if it meant to be Diluted and not Deodorized or Denarcotized

Noscapine A benzylisoquinoline alkaloid from plants of the Papaveraceae family, Without significant painkilling properties. This agent is primarily used for its antitussive effects. Noscapine is currently under investigation for use in the treatment of several cancers including prostate and hypoxic ischemia in stroke patients. In cancer treatment, noscapine appears to interfere with microtubule function, and thus the division of cancer cells in a way similar to the taxanes.

In stroke patients, noscapine blocks the bradykinine b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine. Studies are currently underway to assess the effectiveness of this drug in cancer and stroke treatment. Noscapine is non-addictive, widely available, has a low adverse effect incidence, and is easily administered orally, thus it has great potential for use, especially in developing countries

Noscapine can survive the manufacturing processes of heroin and can be found in street heroin. This is useful for law enforcement agencies, as the amounts of contaminants can identify the source of seized drugs. The average noscapine concentration in street heroin made from opium extracts is around 8%.

Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine. Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants looked for in urine drug screen alongside noscapine are papaverine and acetylcodeine.

Laudanum remains available by prescription in the United States and the United Kingdom, although today the drug's therapeutic indications are generally confined to controlling diarrhea, alleviating pain, and easing withdrawal symptoms in infants born to mothers dependent to opiates. While the terms laudanum and tincture of opium are generally interchangeable, in contemporary medical practice, the latter is used almost exclusively.

Laudanum remained largely unknown until the 1660s when an English physician named Thomas Sydenham (1624–1689) compounded a proprietary opium tincture that he also named laudanum, although it differed substantially from the laudanum of Paracelsus. In 1676 Sydenham published a seminal work, Medical Observations Concerning the History and Cure of Acute Diseases , in which he promoted his brand of opium tincture, and advocated its use for a range of medical conditions.

Thomas Sydenham Became the undisputed master of the English medical world and was known as 'The English Hippcrates’.

By the 18th century, the medicinal properties of opium and laudanum were well-known. Several physicians, including John Jones, John Brown, and George Young, the latter of whom published a comprehensive medical text entitled Treatise on Opium extolled the virtues of laudanum and recommended the drug for practically every ailment. Dr Brown would drink it while giving lectures to medical students.

The Brunonian system of medicine A theory of medicine regarded and treated diseases as caused by defective or excessive excitation. It was developed by the Scottish physician John Brown and is outlined in his 1780 publication Elementa Medicinae . Although Brown's theory never became very popular in Britain, it had some success in America, Italy, and the German-speaking part of Europe. In 1802, a riot between Brunonian and non-Brunonian students of medicine at the University of Göttingen was stopped by a cavalry charge.

Opium, and after 1820, morphine, was mixed with everything imaginable: mercury, hashish, cayenne pepper, ether, chloroform, belladonna, whiskey, wine and brandy.

"To understand the popularity of a medicine that eased--even if only temporarily--coughing, diarrhea and pain, one only has to consider the living conditions at the time." In the 1850s, "cholera and dysentery regularly ripped through communities, its victims often dying from debilitating diarrhea." Dropsy, consumption, ague, rheumatism among many others were all too common.

By the 19th century, laudanum was used in many patent medicines to "relieve pain... to allay irritation (my favorite)... to check excessive secretions... to support the system...as a soporific". The limited pharmacopoeia of the day meant that opium derivatives were among the most efficacious of available treatments, so laudanum was widely prescribed for ailments.

Innumerable Victorian women were prescribed the drug for relief of menstrual cramps and vague aches. Nurses also spoon-fed laudanum to infants. The Victorian era was marked by the widespread use of laudanum in Europe and the United States.

Mary Todd Lincoln, for example was a laudanum addict, as was the English poet Samuel Taylor Coleridge, who was famously interrupted in the middle of an opium-induced writing session of Kubla Khan by a “person from Porlock", actually it was his physician stopping by to deliver more laudanum.

Initially a working class drug, laudanum was cheaper than a bottle of gin, because it was treated as a medication for legal purposes and not taxed as an alcoholic beverage. So if still used today, could one use pretax Flex dollars for it?

1563 The Portuguese explorer Garcia da Orta describes opium addiction in India: “ ...there is a very strong desire for it among those who use it.” Early depiction of craving and compulsion.

1576 German physician-botanist Leonhart Rauwolf, in describing the opium traffic among the Turks, Moors and Persians, notes of opium consumers: “ if they leave off somewhat taking it, so that then they feel physically ill.” Early description of opiate withdrawal.

1592 H. van Linschoten of Holland describes opium use in India: “ He that is used to eating it, must eat it daily, otherwise he dies and consumes himself...he that has never eaten it, and will venture to at first to eat as much as those who daily use it, will surely kill him: for I certainly believe it is a kinde of poison.” Early depiction of tolerance.

1655 Physician Acosta (Portugal) notes difficulties experienced by those trying to discontinue opium use --early anticipation of concept of addiction.

1700 In The Mysteries of Opium Reveal’d , English physician John Jones describes the opiate withdrawal syndrome and dependence, saying that “ the effects of sudden leaving off the uses of opium after a long and lavish use therefore [were] great and even intolerable distresses, anxieties and depressions of spirit, which commonly end in a most miserable death, attended with strange agonies, unless men return to the use of opium; which soon raises them again, and certainly restores them.”

Jones concluded his depiction of addiction with the observation that “ the mischief is not really in the drug but in people,” but does note that the addict eventually loses volitional control of his habit.

1793 The British observer Samuel Crumpe compares opium use in Turkey and the Levant to use of wine and liquor in Europe; he says in these countries opium serves as “ the support of the coward, the solace of the wretched, and the daily source of intoxication to the debauchee.”

This view, which also takes hold in the U.S., stresses the exotic nature of the drug and its users and ascribes addiction as a problem of the less civilized.

late 18th/early 19th century Opium as a form of stimulant is a common theme for the theses medical students must write to graduate from America’s few medical schools. An example is John Augustine Smith’s “ Inaugural Dissertation on Opium Embracing its History, Chemical Analysis, and Use and Misuse as a Medicine,” submitted to the faculty of the College of Physicians and Surgeons, University of the State of New York, in 1832.

1803 D. Wilson. An Inaugural Dissertation on the Morbid Effects of Opium on the Human Body. In: Grob, G., Ed ., Origins of Medical Attitudes Toward Drug Addiction in America . New York: Arno Press. Includes cases of the “habitual use of opium” including one submitted by Benjamin Rush

1803 Franklin Scott, Experiments and Observations on the Means of Counteracting the Deleterious Effects of Opium and on the Method of Cure of the Disease Resulting Therefrom. Refers to opium overdose as a disease. Refers to those “habituated to its (opium) use.” Refers to withdrawal: “...among those who have been in the habit of eating opium, if they are at any time deprived of the usual dose, they are rendered miserable...”

1803 Serteurner isolates and describes morphine. This, the first isolation of an alkaloid from a plant , is a key moment in the emergence of modern pharmacology, one focus of which will be the production of new drugs. Though created as medicines, some of these will be used recreationally and will be associated with problems of dependence. Later the Progressive Era concerns about opiate and cocaine use follow closely on the introduction and widespread sales of such compounds as morphine, cocaine, heroin, veronal, and aspirin.

Morphine Is considered to be the prototypical opiate/opioid. It was discovered in 1803 by Fredrich Sertűrner, first distributed by him in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop.

A opiate is usually consider to be based on coming from opium, an opioid is usually considered to be a chemical not occurring in nature.

Friedrich Wilhelm Adam Sertürner Born 19 June 1783 died 20 February 1841 He was a German pharmacist. As a pharmacist's apprentice in Paderborn, he was the first to isolate morphine from opium. He called the isolated alkaloid “morphium" after the Greek god of dreams, Morpheus.

It was not only the first alkaloid to be extracted from opium, but the first ever alkaloid to be isolated from any plant. Thus he became the first person to isolate the active ingredient associated with a medicinal plant or herb. In the years following, he investigated the effects of morphine. However, it only became widely used after 1815.

1822 Thomas De Quincey publishes Confessions of an English Opium-Eater . This work and Samuel Taylor Coleridge’s poem “Xanadu” launch the Romantic image of the aristocratic, bohemian opium user.

1822 John Eberle characterizes opiate withdrawal: “ When the system is entirely free from the influence of the accustomed stimulant, torments of the most distressing kind are experienced.” This is an early statement of the position that opiate withdrawal is a uniquely harrowing physical and mental experience.

1832 W. Smith, An Inaugural Dissertation on Opium, Embracing Its History, General Chemical Analysis and Use and Misuse as a Medicine : “Opium should never be used as a substitute for the ordinary stimulus of wine or spirits: for when it is thus used, it seldom fails to lay the foundation for a long train of morbid symptoms, which, sooner or later, terminate in all the wretchedness, which disease is capable of inflicting...”

1850 Nathan Allen, An Essay on the Opium Trade. “There is no slavery on earth, to be compared to with the bondage into which Opium casts its victims. There is scarcely one known instance of escape from its toils, when once they have fairly enveloped a man.” “It is not the man who eats Opium, but it is Opium that eats the man.”

Francis Rynd (1801-1861) 1844 Introduced the hypodermic method of medication for the relief of pain. This he accomplished by the use of a small gravity device of his own invention. He possessed an extremely modest disposition and allowed a Scotchman named Wood to be given most the credit for priority in this field. Investigators have, however, clearly established since then that honor belongs to Rynd.

In his description of the instrument and its use, he says, in part, “ The smaller instrument is for deep-seated nerves; for though it is not necessary to introduce the fluid into the nerve itself to ease the pain, still the nearer the seat of pain is conveyed the more surely relief is given. The fluid I have found most beneficial is a solaria of morphine in creosote, 10 grains of the former in 1 dram of the latter; six drops of this solution contain 1 grain of morphine and a grain or two may be introduce in cases of sciatica at one operation with the very best effects.”

The hypodermic syringe 1853: Charles Pravaz and Alexander Wood developed a medical hypodermic syringe with a needle fine enough to pierce the skin. Shortly thereafter, the first recorded fatality from a hypodermic-syringe induced overdose was Wood's wife from self administered morphine. This is widely reported but some historians say this is a myth and others that it is a fact.

This new instrument was developed with the promise to reduce morphine addiction By the reduced doses required via interjection compared to oral use. Many, if not all “new tools” in the treatment of addiction, started as “cures” and ended as curses.

1857 Fitzhugh Ludlow publishes The Hasheesh Eater , an American work in the genre pioneered by De Quincey and Coleridge. He writes of opiates, “ The emasculation of the will itself, ...is in reality the most terrible characteristic of the injury wrought by these agents.”

Ludlow also wrote about his travels across America on the overland stage to San Francisco, Yosemite and the forests of California and Oregon, in his second book, The Heart of the Continent. He was also the author of many works of short fiction, essays, science reporting and art criticism. He devoted many of the last years of his life to attempts to improve the treatment of opiate addicts.

The idea that opiates debase the will and sap the capacity for moral action becomes the foundation of the view that addiction is a moral vice rather than an illness.

1860 Oliver Wendell Holmes, Sr., dean of Harvard Medical School, blames physicians for causing opiate addiction through careless prescribing.

He characterizes the problem as especially serious in the Western states where, he says, “the constant prescription of opiates by certain physicians...has rendered the habitual use of that drug in that region very prevalent... A frightful endemic demoralization betrays itself in the frequency with which the haggard features and drooping shoulders of the opium drunkards are met with in the street.”

By claiming the problem lies with Western physicians who were likely trained in proprietary medical schools rather than with elite Eastern physicians like himself, Holmes’s statement reflects growing tensions and rivalries within the medical profession in nineteenth century America.

1861-1865 The use of opium and morphine in the treatment of disease and injury is widespread during the Civil War and the use of the hypodermic syringe becomes more widespread by the end of the War.

While opium addiction will in later years become labeled the “soldier’s disease” because of such use, there are very few accounts of soldiers addicted during the war, but both disease and injury create a large vulnerable population in the post-civil war patent medicine era.

The Soldier’s Disease The Army’s Disease Leading some to say The brand name Heroin Comes from “Hero in” or a drug for heroes Bayer says the name was derived from the German word " heroisch " (heroic) due to its perceived "heroic" effects upon a user.

It was chiefly developed as a morphine substitute for cough suppressants that did not have morphine's addictive adverse effects. Morphine at the time was a popular recreational drug, and Bayer wished to find a similar but non-addictive substitute to market. However, contrary to Bayer's advertising as a "non-addictive morphine substitute," heroin would soon have one of the highest rates of addiction amongst its users.

1864 Edward Parrish, in his A Treatise on Pharmacy notes how citizens who would not misuse alcohol take opium until “they become victims to one of the worst habits.”

1864 The first case of morphine addiction involving the use of the hypodermic syringe is reported.

1867 Fitz Ludlow What Shall They Do to Be Saved? Harper’s Magazine. “Now, such a man (opium addict) is a proper subject, not for reproof, but for medical treatment. The problem of this case need embarrass nobody. It is as purely physical as one of small-pox. When this truth is as widely understood among the laity as it is known by physicians, some progress may be made in staying the frightful ravages of opium among the present generation.” References to “opium disease” throughout the article

Harper’s is the second-oldest continuously published monthly magazine in the U.S. ( Scientific American is the oldest)

1870 Sir Thomas Clifford Allbutt of Cambridge expresses his alarm at so few warnings about the hypodermic injection of morphine.

1870s Physiological study of effects of morphine administration, including animal studies, is carried out in American and European laboratories. Doses, duration of action, and route of administration are correlated with physiological effects such as respiratory depression.

Warnings about addictiveness of morphine and a shifting cluster of other drugs begin to be common in the medical literature.

1870s-90s Physicians prescribe morphine for wide ranging indications, reflecting the range of morphine’s physiological actions and prevailing ideas about disease. Morphine is known to relieve pain, promote sleep, ease anxiety, combat diarrhea, reduce coughing.

Humoral models of disease favor medications with a broad range of systemic effects. In the competitive American medical scene, “regular” physicians distinguish themselves by prescribing drugs, like morphine, which produce clear physiological effects.

As all medications are available for purchase without prescription, people medicate themselves to relieve symptoms, according to popular notions of disease. Examples: Women take morphine to relieve menstrual cramps, and mothers teach their daughters to do this. Women take morphine to ease the anxieties and pressures connected with their social roles.

1871 George M. Beard estimates there are 150,000 opiate addicts in the U.S. Beard becomes famous for elaborating the concept of neurasthenia, a condition he believes to afflict those engaged in the complex mental tasks associated with an urbanizing and industrializing civilization of growing complexity.

He remains the chief exponent of the view that higher types bear a special susceptibility to nervous conditions, including addiction. This idea contrasts with an increasingly common tendency in the U.S. to associate opiate use with stigmatized groups and a view of addiction disease as occurring independently of individuals’ social status or character.

1872 H. Brown, An Opium Cure: Based on Science, Skill and Matured Experience . Described “Chronic Opium Disease” as a new and “intricate” disease. “Opium is often taken for the relief of suffering from chronic diseases until the opium habit has become confirmed and the two diseases reign together.” Note habit and disease used interchangeably.

1874 Heroin is invented but is not marketed until 1898.

1875-1877 Eduard Levinstein publishes a series of articles in Germany that call attention to the problem of morphine addiction. His was one of first studies on narcotic addiction relapse A rate he estimated as high as 75%.

1877 G.F. Foote Inebriety and Opium Eating: In Both Cases a Disease with Method of Treatment and Conditions of Success . Foote began treating alcohol and opium addicts in his private medical practice in 1848 and then opened the Dr. Foote’s Home in Stamford, CT

“ It should be assumed on the part of the physician, that the habitual use of the alcoholic or narcotic element has diseased the system...in other words, has produced a physical and functional derangement of the organism, and that such has reduced the digestive, pulmonic, urinary, and nervous systems, to a condition that is thoroughly morbid.”

“This is ever accompanied with a desire for alcohol or opium...which in the first instance was but slight, but grew stronger and stronger by indulgence, until is has been made absolutely irresistible.”

1878 Morris, F. Baldwin The Panorama of a Life, And Experience in Associating and Battling with Opium and Alcoholic Stimulants . Refers to “opium and alcoholic inebriacy” and opium and alcohol “habits” interchangeably. Includes chapter entitled “Alcoholism”

1878 Eduard Levinstein’s The Morbid Craving for Morphia is published in Germany, noting an “uncontrollable desire” for morphine and that the injudicious use of morphine produces a “diseased state.”

1878 The New York Times estimates there are 200,000 opiate addicts in the U.S. It warns of a dangerous fad, especially among society women, of injecting morphine; it terms this behavior a vice.

1880 In the late 1870s and early 1880s, there is a vogue for a treatment method developed by Edouard Levinstein. It consists of abrupt withdrawal from opiates, physical restraints, and drugs to control symptoms. Patient resistance to its harsh methods quickly lead to its abandonment.

A method of gradual withdrawal of opiates over the course of a week, with other medications to relieve symptoms, becomes standard. Various drugs go through brief periods of popularity as substitutes for morphine, including cocaine and cannabis.

1880 C.W. Earle (MD) The Opium Habit. Chicago Medical Review, 2:442-446, 493-498. “It is becoming altogether too customary in these days to speak of vice as disease, and to excuse the men and women for the performance of indulgence of certain acts which not only ruin themselves and families but brings burden on the community...That the responsibility of taking the opium or whiskey...is to be excused and called a disease, I am not willing for one moment to admit, and I propose to fight this pernicious doctrine as long as is necessary.”

1881 H. Kane. Drugs That Enslave: The Opium, Morphine, Chloral and Hashish Habits . This is a medical text filled with symptom descriptions and detailed treatment protocol; refers to addiction throughout as a “habit” or “vice.” “ Some persons are undoubtedly born with, and some acquire, this craving for some narcotic stimulant.” “ A higher degree of civilization, bringing with it increased mental development among all classes, increased cares, duties and shocks, seems to have caused the habitual use of narcotics, once a comparatively rare vice among Christian nations, to have become alarmingly common.”

This statement typifies one of two strands of thinking about addiction as a mental or psychiatric condition in the late nineteenth century: those who engage the brainwork necessary for an advanced civilization suffer from delicate nervous systems which makes them susceptible to nervousness, breakdowns, or addiction. A separate strain ascribes a tendency to addiction to those who lack finer qualities and whose families pass along a host of heritable negative conditions including addiction.

Kane reflects this view as well when he ascribes the tendency of Chinese to achieve a dreamy reverie with opium to racial characteristics. The common thread between these disparate views is that the individual user's makeup or character determines drug effects and susceptibility to addiction.

1881 Fred Hubbard, M.D. The Opium Habit and Alcoholism . “The drug (opium) mislead its victims, regarding their own ability to maintain mastery over it...There is no shadow cast before, as a warning of the coming misery.” “Our experience suggests that a constitutional condition exists with some persons which predisposes them to this class of habits, making it necessary for them to exercise their will-power and to keep a continual watch upon themselves to curb all desire for liquor or the narcotics.”

Hubbard writes, “Many patients feel ashamed of being addicted to the drug, and wishing to retain respect, will tell the physician of some imaginary trouble as the cause of the habit.” “The shame felt by addicts, the barrier such shame creates to seeking help or treatment, and the recourse to manufactured complaints to try to obtain drugs from physicians all become standard features of addict-physician relations.”

1882 E. Sell,The Opium Habit: Its Successful Treatment by the Avena Sativa. Refers to opium addiction as “dreadful habit” Reproduces letter from husband of a woman who became addicted following use of morphine for stomach disorder. He reports that “morphine was found to be palliative, and as such was continued until the drug produced its own disease ...” (Italics in original)

Avena Sativa The common oat is a species of Cereal grain grown for its seed, which is known by the same name, usually in the plural, unlike other grains.

1884 C. H. Hughes writes, “ The friends and family of an opium habituate are most familiar with the degrading character of the slavery of the mind and nervous system which opium entails.” “ They realize how lost to the family circle as a real member of the household he or she has become, and whether it be father or mother, sister or brother, it is but natural that they should strive to reclaim that which is lost, or if not lost, at least estranged in many of those familiar mental traits with which are blended family love, esteem and reverence.”

This statement reflects the impact of addiction on family members and other intimate associates of the addict. Families’ despair over the addict’s behavior, including that which places drug seeking and drug use over family obligations, is a frequent precipitant of the decision to seek treatment for drug problems.

1885 J. M. Hull reports to the Iowa State Board of Health that a survey of druggists revealed 235 opiate addicts. These include 18 physicians; 26 who use morphine hypodermically; 86 are males; 129 females.

1885 Asa Meyerlet. Notes on the Opium Habit. Refers to “opium habit” throughout; no disease references.

1887 Samuel B Collins, MD: A Treatise on the Habitual Use of Narcotic Poison . Advertising essay for his “Painless Cure for the Opium Disease”

1888 Dr. Norman Kerr coins the term “narcomania” to capture the frenzied drugseeking behavior of the addict.

1890s Addiction to opiates and, to a lesser extent, cocaine, has become a widely recognized problem. Many states pass laws restricting sale of these drugs except as authorized by a physician. Loopholes exist in exemptions allowing amounts below a certain dose threshold to be sold without restriction.

1890 Materia medica and therapeutics textbooks typically couch the addiction risk as associated with particular medical indications, such as prolonged neuralgia, rather than as a risk present whenever opiates are prescribed for lengthy periods. The 35 long courses of treatment and typical hospital stays of up to three months create risks of addiction for patients. The textbooks also typically characterize opiate addicts as liars who have lost all moral sense.

Such statements represent a growing shift from sympathetic to punitive views of addicts that will parallel the demographic shift of opiate addiction from quasi-medical use by middle-aged, middle-class women to recreational use by young men connected to the vice districts of American cities. They also reflect the problematic nature of addicts as patients to physicians in general practice. The view that addicts are liars and cannot be trusted typifies materia medica and therapeutics textbooks through the 1920s.

1894 Dr. Bailey P. Key Good Advice and Practical Hints Relative to the Opium, Morphine, Chloral, Whiskey, Cocaine and Kindred Habits (or Diseases) and Their Treatment and Cure . (Advertising Pamphlet).

1894 Kerr, Norman, MD Inebriety or Narcomania: Its Etiology, Pathology, Treatment and Jurisprudence . “ ...let me define inebriety as a constitutional disease of the nervous system, characterized by a very strong morbid inexpressibly intense involuntary morbid craving for the temporary anaesthetic relief promised by every form of narcotic.”

“Inebriety is so varied in form, so subtle in operation, so intricate in development, and so complex in causation, that its treatment is no easy task.”

1895 Henry G. Cole ascribes the prevalence of opiate and alcohol addiction to the quickening pace and growing complexity of industrial life.

1896 Wilson and Eshner American Textbook of Applied Therapeutics . “ Morphinism is a disease both of the body and the mind, caused by chronic poisoning by morphin. When the disease is developed there exists an irresistible craving for the drug, and it is this artificial appetite that is the difficulty to overcome in the treatment.”

1898 The Bayer company puts heroin on the market (same year as Aspirin) as an antitussive. As a sniffable powder marketed as a cough remedy, it quickly gains favor as a recreational drug among young men (and, to a lesser extent, women) in urban neighborhoods.

1898 The U.S. enters and quickly wins the Spanish-American War and gains new territories, including the Philippines. Missionary observers are appalled at the levels of opium addiction they find there and see this problem as an obstacle to economic modernization for the islands. Similarly, missionaries portray the prevalence of opium use in China as a sign of China’s backwardness.

These concerns help launch the international missionary movement which sparks domestic efforts to pass federal legislation banning opiates, on the grounds that American missionaries could hardly urge other countries to pass prohibitive legislation when the U.S. lacked such laws. This lead to the Harrison Narcotics Act in 1914

1899 W. Hale White, in the fourth edition of his Materia Medica: Pharmacy, Pharmacology and Therapeutics , characterizes addicts as liars who cannot be trusted.

A federal prison in Kentucky was a temporary home for thousands, including Sonny Rollins, Peter Lorre and William S. Burroughs as well as a lab for addiction treatments such as LSD

Hippy Sippy Was a candy introduced in the late 1960s. It derived its name from its packaging: small multi-colored pellets contained in a toy package syringe. The intent was to mimic drug usage in the ”hippie” culture, primarily through the toy syringe being a reminder of heroin, and secondarily through the multi-colored candy being a reminder of uppers and downers.

Included was a button with the phrase "Hippy Sippy says I'll try anything!" printed on it. Hippy Sippy was immediately controversial, and outraged many people. It was promptly removed from the market, but is still remembered due to its cultural shock value. More recently, the name was adopted by saxophonist Hank Mobley for his song Hippy Sippy Blues .

O O OH N CH 3 morphine H C 3 codeine

O O O N CH 3 H C 3 codeine H hydrocodone

O O O N CH 3 H C 3 hydrocodone

O O O N CH 3 H C 3 H codone hydro oxy OH

O O O N CH 3 H C 3 H codone oxy OH

O O O N CH 3 H morphine H H hydromorphone

O O O N CH 3 H H hydromorphone O N

O O O N CH 3 H H morphone OH hydro oxy

O O O N CH 3 H H morphone OH oxy

O O O N CH H H H morphine CH=CH 2 3 2 OH naloxone

O O O N CH H H CH=CH 2 2 OH naloxone Narcan

O O O N CH H H CH=CH 2 3 2 OH naloxone naltrexone

O O O N CH H H 2 OH naltrexone Revia, Vivitrol

O O O N CH H H H 2 OH naltrexone C CH 3 C(CH 3 ) 3 OH 3 buprenorphine

O O O N CH H H H 2 OH C CH 3 C(CH 3 ) 3 OH 3 buprenorphine

CH 3 CH 2 OC O N-CH 3 meperidine

CH 3 CH 2 O N-CH 3 2 CH 2 - O N C fentanyl

C O C CH 3 CH 2 CH 2 CH CH 3 N CH 3 CH 3 methadone

A persistent but untrue urban legend claims that the trade name of Methadone "Dolophine" was coined in tribute to Adolf Hitler by its German creators, and it is sometimes even claimed that the drug was originally named "adolphine" or "adolophine" or "Dolphamine". The claim is still presented as fact by Church of Scientology literature and was repeated by actor and vocal Scientologist Tom Cruise in a 2005 Entertainment Weekly interview.

However, as the magazine pointed out, this is not true: the name "Dolophine" was in fact created after the war by the American branch of Eli Lilly and the pejorative term "adolphine" (never an actual name of the drug) appeared in the United States in the early 1970s.

C O C CH 3 CH 2 CH 2 CH CH 3 N CH 3 CH 3 2 O methadone propoxyphene

11/19/2010 FDA had it removed from the market due to heart rhythm abnormalities.

O O O N CH 3 H H COC COC 3 3 diacetyl morphine heroin

It is common for people to experience pleasurable and even euphoriant effects from eating capsaicin-flavored foods. FolkloreFolklore among self-described “chiliheads" attributes this to pain-stimulated release of endorphins, a different mechanism from the local receptor overload that makes capsaicin effective as a topical analgesic. In support of this theory, there is some evidence that the effect can be blocked by naloxone and other compounds that compete for receptor sites with endorphins and opiates.

Diego Alvarez Chanca, a physician on Columbus' second voyage to the West Indies in 1493, brought the first chili peppers to Spain, and first wrote about their medicinal effects in 1494.

Qutenza® has proven, long-lasting pain relief in two 12-week, pivotal postherpetic neuralgia trials

1997, a research team led by David Julius of UCSF showed that capsaicin selectively binds to a protein known as TRPV1 that resides on the membranes of pain and heat sensing neurons. TRPV1 is a heat activated calcium channel, which opens between 37 and 45 °C.

When capsaicin binds to TRPV1, it causes the channel to open below 37 °C which is why capsaicin is linked to the sensation of heat. Prolonged activation of these neurons by capsaicin depletes presynaptic substance P, one of the body's neurotransmitters for pain and heat. Neurons that do not contain TRPV1 are unaffected.

The result appears to be that the chemical mimics a burning sensation, the nerves are overwhelmed by the influx, and are unable to report pain for an extended period of time. With chronic exposure to capsaicin, neurons are depleted of neurotransmitters, leading to reduction in sensation of pain and blockade of neurogenic inflammation. If capsaicin is removed, the neurons recover.

Other possible medical uses include diabetes: In DM 1 capsaicin was injected subcutaneously affecting pancreatic sensory nerves of mice with Type 1 diabetes because of a suspected link between the nerves and diabetes. In DM 2 as a treatment for peripheral neuropathy.

Clifford Woolf, the Richard J. Kitz Professor of Anesthesia Research at Harvard Medical School, has suggested using capsaicin to deter misuse of certain extended-release drugs such as OxyContin and Adderall XR. When taken as prescribed these type of drugs release their active chemical over time, but when crushed and snorted, taken as a suppository, chewed, or injected, the larger than normal dosage is absorbed all at once and a much stronger effect is produced that can be highly habit forming and dangerous due to the higher risk of overdose.

Woolf has argued that adding capsaicin into the capsules would be a safe way to deter misuse. A person taking the capsule in the prescribed way ( i.e., swallowing it whole) would suffer no ill effects from the additive. However, a person crushing it would expose the irritant. Anyone then chewing it, snorting it, or injecting it would be exposed to the full power of the chemical. "Imagine snorting an extract of 50 jalapeño peppers and you get the idea," Woolf said in an interview with the Harvard University Gazette. As of 2006, Woolf's proposal is still in the preliminary stages of development and the additive has not yet entered the production stage

Placenta for Pain Relief: Placenta ingestion by rats enhances y- and n-opioid antinociception, but suppresses A-opioid antinociception Ingestion of placenta or amniotic fluid produces a dramatic enhancement of centrally mediated opioid antinociception in the rat. The present experiments investigated the role of each opioid receptor type in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF).

Antinociception was measured on a 52 jC hotplate in adult, female rats after they ingested placenta or control substance (1.0 g) and after they received an intracerebroventricular injection of a y-specific ([D-Pen2,D-Pen5]enkephalin (DPDPE); 0, 30, 50, 62, or 70 nmol), A-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or n-specific (U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist.

The results showed that ingestion of placenta potentiated y- and n-opioid antinociception, but attenuated A-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex provides an important basis for understanding the intrinsic pain-suppression mechanisms that are activated during parturition and modified by placentophagia, and important information for the possible use of POEF as an adjunct to opioids in pain management.

10102323454577 is the smallest 14-digit prime number that follows the rhyme scheme of a Shakespearean sonnet (ababcdcdefefgg). Just because.

Or Sam Opiates &amp; Opioids 04 19 2011

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