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Chapter 13 Opioids. Opioids. Opium is a naturally occurring substance derived from the poppy plant

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Chapter 13




  • Opium is a naturally occurring substance derived from the poppy plant
    • Opium (poppy tears, lachryma papaveris) is the dried latex obtained from the opium poppy (Papaver somniferum). Opium contains approximately 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine. (source)

Opium Cultivation

  • Opium is produced and available for collection for only a few days of the plant’s life, between the time the petals drop and the seed-pod matures.
  • Opium harvesters make shallow cuts into the unripe seedpods
    • During the night a white substance oozes from the cuts, oxidizes to a red- brown color, and becomes gummy. In the morning the resinous substance is carefully scraped from the pod and collected in small balls.
    • This raw opium forms the basis for the opium medicines that have been used throughout history and is the substance from which morphine is extracted and then heroin is derived.
    • Morphine extracted from raw opium
    • Heroin is derived from morphine

Opioids (relating to the drugs that are derived from opium)

  • Major effects of opioids:
    • Relieves pain and suffering (analgesics)
    • Delivers pleasure and relief from anxiety
    • Opioid narcotics are also used to treat conditions not related to pain. For example:

these drugs suppress the coughing (antitussive) center of the brain, so they are effective antitussives. Codeine, a natural opioid narcotic, is commonly included in cough medicine. In addition, opioid narcotics slow the movement of materials through the intestines, a property that can be used to relieve diarrhea or can cause the side effect of constipation


History of Opium

  • Cultivation of opium poppies for food, anaesthesia, and ritual purposes dates back to at least the Neolithic Age (new stone age).
  • A 6000-year-old Sumerian tablet has an ideograph for the poppy shown as “joy” plus “plant,” suggesting that the addicting properties of this substance have been appreciated for millennia
  • The Sumerian, Assyrian, Egyptian, Indian, Minoan, Greek, Roman, Persian and Arab Empires all made widespread use of opium, which was the most potent form of pain relief then available, allowing ancient surgeons to perform prolonged surgical procedures. (source)

History of Opium

  • The Greek god of sleep, Hypnos, and the Roman God of sleep, Somnus, were portrayed as carrying containers of opium pods, and the Minoan goddess of sleep wore a crown of opium pods.
  • During the so-called Dark Ages that followed the collapse of the Roman Empire, Arab traders actively en- gaged in traveling the overland caravan routes to China and to India, where they introduced opium. Eventually, both China and India grew their own poppies. (1)

Hypnos and Thánatos, Sleep and His Half-Brother Death : by John William Waterhouse


History of Opium

  • Europe / China
    • Opium used widely beginning in the sixteenth century. By the late 1690s, opium was being smoked and used for diversion. The Chinese government, fearful of the weakening of national vitality by the potent opiate narcotic, outlawed the sale of opium in 1729. The penalty for disobedience was death by strangulation or decapitation. (1)
    • Despite these laws and threats, the habit of opium smoking became so widespread that the Chinese government went a step further and forbade its importation from India, where most of the opium poppy was grown. (1)

History of Opium

  • Europe / China
    • In contrast, the British East India Company (and later the British government in India) encouraged cultivation of opium. British companies were the principal shippers to the Chinese (1)
    • During the next 120 years, a complex network of opium smuggling routes developed in China with the help of local merchants, who received substantial profits, and local officials, who pocketed bribes to ignore the smugglers. (1)

History of Opium

  • The Opium Wars (Part 1)

Everyone involved in the opium trade, but particularly the British, continued to profit until the Chinese government ordered the strict enforcement of the edict against importation. Such actions by the Chinese caused conflict with the British government and helped trigger the Opium War of 1839 to 1842 (British Victory)

Because of the war, the island of Hong Kong was ceded to the British, and an indemnity of $6 million was imposed on China to cover the value of the destroyed opium and the cost of the war. (1)

war broke out between the British and Chinese


History of Opium

  • The Opium Wars (Part 2)

In 1856, a second Opium War broke out. Peking was occupied by British and French troops, and China was compelled to make further concessions to Britain. The importation of opium continued to increase until 1908, when Britain and China made an agreement to limit the importation of opium from India. (1)

Pressure grew and eventually war broke out between the British and Chinese


History of Opium / Morphine

  • American Opium Use

In 1803, a young German named Friedrich Sertürnerextracted and partially purified the active ingredients in opium. The result was 10 times more potent than opium itself and was named morphine after Morpheus, the Greek god of dreams. This discovery increased worldwide interest in opium. By 1832, a second compound had been purified and named codeine, after the Greek word for “poppy capsule”. (1)

Pressure grew and eventually war broke out between the British and Chinese


History of Opium / Morphine

  • American Opium Use

The opium problem was aggravated further in 1853, when Alexander Wood perfected the hypodermic syringe and introduced it first in Europe and then in America. (1)

Wood perfected the syringe technique with the intent of preventing morphine addiction by injecting the drug directly into the veins rather than by oral administration.Unfortunately, just the opposite happened; injection of morphine increased the potency and the likelihood of dependence(1)

Pressure grew and eventually war broke out between the British and Chinese


History of Opium / Morphine

  • American Civil War and Post War-time Abuse

The hypodermic syringe was used extensively during the Civil War to administer morphine to treat pain, dysentery, and fatigue. A large percentage of the soldiers who returned home from the war were addicted to morphine. Opiate addiction became known as the “soldier’s disease” or “army disease.”(1)

Pressure grew and eventually war broke out between the British and Chinese


History of Opium / Morphine

By 1900, an estimated one million Americans were dependent on opiates. This drug problem was made worse because of (1) Chinese laborers, who brought with them to the United States opium to smoke (it was legal to smoke opium in the United States at that time); (2) the availability of purified morphine and the hypodermic syringe; and (3) the lack of controls on the large number of patent medicines that contained opium derivatives (1)

Pressure grew and eventually war broke out between the British and Chinese


History of Opium / Morphine

Until 1914, when the Harrison Narcotic Act was passed (regulating opium, coca leaves, and their products), the average opiate addict was a middle-aged, Southern, white woman who functioned well and was adjusted to her role as a wife and mother. She bought opium or morphine legally by mail order from Sears and Roebuck or at the local store (1)

Pressure grew and eventually war broke out between Video on the history of opioids and Chinese



  • Morphine is the primary active ingredient in opium
    • First isolated in 1806
    • Named morphium after Morpheus, the god of dreams
    • 10 times as potent as opium
  • Codeine is a secondary active alkaloid
    • First isolated in 1832
    • Named codeine from the Greek word for “poppy head”


  • Morphine use spread due to two developments
  • Technological development:
    • 1853: Hypodermic syringe allowed delivery of morphine directly into the blood
  • Political development:
    • Widespread use during war provided relief from pain and dysentery
      • Veterans returned dependent on morphine
      • Dependence was later called “soldier’s disease” or “army disease”


  • Heroin(diacetylmorphine)
    • 1874: two acetyl groups were attached to morphine
    • 1898: marketed as Heroin (brand name) by Bayer
    • Was called the “heroic” drug
  • Three times as potent as morphine
    • due to increased lipid solubility of the heroin molecule
    • this increased solubility allowed rapid transfer to the brain
  • Originally Marketed as a non-addictive cough suppressant
    • Replacement for codeine and morphine
    • Later linked to dependence

Opioid Abuse Before Harrison Act

  • Three types of opioid dependence in the U.S.:
    • In the second half of the 19th century, three forms of opioid dependence were developing in the United States.
    • The long useful oral intake of opium, and then morphine, increased greatly as patent medicines became a standard form of self-medication.
    • After 1850, Chinese laborers were imported in large numbers to the West Coast, and they introduced opium smoking to this country.
    • The last form, medically the most dangerous and ultimately the most disruptive socially, was the injection of morphine.

Opioid Abuse Before Harrison Act

  • Initially, opioid dependence was not viewed as a major social problem
    • Opium smoking was limited to certain ethnic groups
    • Patent medicines were socially acceptable
    • Opioid dependence was viewed as a “vice of middle life”
  • Typical user:
    • 30-to-50-year-old middle class white woman
    • Drugs purchased legally in patent medicines

Opioid Abuse After Harrison Act

  • Enforcement of the 1914 Harrison Act made opioids difficult to obtain
    • Only sources of drugs were illegal dealer
  • Resulted in changes in opioid use patterns
    • Oral use declined
    • Primary remaining group of users were those who injected morphine or heroin
    • Cost and risk of use increased
      • Thus, the most potent method (intravenous injection of heroin) was favored
    • In 1915, the United States Supreme Court decided that possession of smuggled opioids was a crime, and thus users not obtaining the drug from a physician became criminals. Under the influence of the media and the Federal Government, by the 1920’s, habitual opioid users were now viewed as degenerates and criminals.

Opioid Abuse After Harrison Act

  • The 1960s and 70s
    • Heroin use further increased in large cities
    • The most visible abusers were African American or Latino and because of the association of heroin use with crime, the white majority expressed little patience or tolerance toward people who were dependent on heroin.
    • In New York, users were prosecuted under the Rockefeller Drug Laws (1973). These laws created mandatory minimum prison sentences of 15 years to life for possession of four ounces of drugs such as heroin. (Modified by Governor Patterson in 2009)
  • After WWII
    • Heroin use slowly increased in the lower- class, slum areas of the large cities. Heroin was inexpensive in this period; a dollar would buy enough for a good high for three to six people; $ 2-a-day habits were not uncommon.
    • As the 1950s passed, heroin use spread. As demand in-creased, so did both the price and the amount of adulteration.

Heroin Use in Vietnam

  • Heroin in Vietnam was relatively
    • Inexpensive - Ten dollars would buy about 250 mg( 10 injections , US cost $500)
    • Heroin was about 95 percent pure and almost openly sold in South Vietnam
    • Easy to obtain
  • About 5% of personnel tested positive for opioids
    • Due to the purity, most users smoked or sniffed the drug
    • Most users stopped when they returned to the U.S.
    • Most users were in the lower ranks
  • Vietnam experience showed
    • Under certain conditions, (availability and low cost of the drug, limited sanctions, stress) a relatively high percent of individuals will use opioids recreationally
    • Opioid dependence is not inevitable among occasional users

Abuse of Prescription Opioids

  • Popular prescription opioids
    • Hydrocodone (Vicodin, Lortab)
    • Oxycodone (Oxycontin, Percocet)
  • Prevalence of use:
    • 2010: 12 million Americans reported past year use (Compared to 1.5 mil using cocaine and 17 mil using marijuana)
    • Routes of administration include oral, insufflation, injection
  • Safety concerns:
    • DAWN(Drug Abuse Warning Network) data: prescription opioids rank 3rd for ER visits and 1st for deaths
    • Most opioid overdoses occur in combination with other sedatives such as alcohol
    • The bottom line is that the use of prescription pain reliever has not dramatically increased in recent years, but there appears to be a real concern about the potential for toxicity when the drugs are misused.

Opioid Chemical Characteristics

  • Narcotic agents isolated or derived from opium

Raw opium contains about 10 percent morphine by weight and a smaller amount of codeine. The addition of two acetyl groups to the morphine molecule results in diacetylmorphine, or heroin.


Prescription Narcotic Analgesics

  • Natural products
    • Morphine
    • Codeine
  • Semi-synthetics
    • Heroin
  • Synthetics
    • Methadone
    • Meperidine
    • Oxycodone
    • Oxymorphone
    • Hydrocodone
    • Hydromorphone
    • Dihydrocodeine
    • Propoxyphene
    • Pentazocine
    • Fentanyl

Medicinal chemists have worked hard over the decades to produce compounds that would be effective painkillers, trying to separate the analgesic effect of the opioids from their dependence-producing effects. Although the two effects could not be separated, the research has resulted in a variety of opioids that are sold as pain relievers, and some as powerful anesthetics.


Opioid Antagonists

  • Drugs that block the action of opioids
    • Examples: Naloxone (Narcan) and nalorphine
  • Effects
    • Reverse depressed respiration from opioid overdose
    • Precipitate withdrawal syndrome
    • Prevent dependent individuals from experiencing a high from subsequent opioid use
  • Harm reduction strategy
    • Several U.S. cities have initiated programs that provide naloxone to heroin users
    • Results in fewer overdose deaths

Mechanism of Action

  • Naturally occurring opioid-like neurotransmitters
    • Enkephalins: morphine-like neurotransmitters found in the brain and adrenals
    • Endorphins: morphine-like neurotransmitters found in the brain and pituitary gland
  • Endogenous opioids and opioid drugs are agonists of several types of opioid receptors
    • mu and kappa (play a role in pain perception)
    • delta (function not well understood)

Beneficial Uses

  • Pain relief
    • Reduces the emotional response to pain
    • Diminishes the patient’s awareness of, and response to, the aversive stimulus
    • Although one of the characteristics of these drugs is their ability to reduce pain without inducing sleep, drowsiness is not uncommon after a therapeutic dose.
  • Treatment of intestinal disorders
    • Counteracts diarrhea and the resulting dehydration
    • Decreases number of peristaltic contractions
    • Often results in constipation in patients taking the drugs for pain relief
  • Cough suppressant
    • Codeine has long been used for its antitussive properties
    • Dextromethorphan (OTC antitussive) is an opioid analogue that is somewhat more selective in its antitussive effects.

Dependence Potential

  • Tolerance
    • Tolerance develops to most of the effects of the opioids, although with different effects tolerance can occur at different rates.
    • Higher doses needed to maintain effects
    • Cross-tolerance exists among all the opioids - Tolerance to one reduces the effectiveness of each of the others.
    • Some of the body’s tolerance to opioids results from conditioned reflex responses to the stimuli associated with taking the drugs.
  • Physical dependence
    • Opioid withdrawal is unpleasant but rarely life-threatening
    • Withdrawal symptoms can be prevented with any opioid agonist

Opioid Withdrawal Symptoms

Approximate hours after previous dose


Toxicity Potential

  • Acute toxicity
    • Opioids depress respiration -The basis for this effect is that the respiratory centers become less responsive to carbon dioxide levels in the blood.
    • Effects with alcohol are additive
    • Occasionally, nausea and vomiting - Opioid agonists also stimulate the brain area controlling nausea and vomiting, which are other frequent side effects.
    • Can be counteracted with naloxone
  • Chronic toxicity
    • Associated with injection - Many street users do suffer from sores and abscesses at injection sites, but these can be attributed to the lack of sterile technique.
    • Infections and the spread of blood-borne diseases (hepatitis, and HIV)

Life of a Heroin User

  • “No Vacation”
    • Three to four injections needed daily to prevent withdrawal – Begin to feel ill after six to eight hours from previous dose
  • Expensive habit
    • cost of drugs and paraphernalia
  • Health concerns
    • Risk of overdose due to variable potency of different batches
    • Skin infections
    • Blood-borne infections
  • Important note: A large number of heroin “mature out”
    • Gradually stop using the drug


  • Intense pleasure unequaled by any other experience
    • Some people report nausea and discomfort but continue to use
    • Then, tolerance to negative effects develops more rapidly compared to euphoric effects
  • Withdrawal is always excruciating
    • Withdrawal is often similar to a mild case of the intestinal flu
  • After one injection you are hooked for life
    • Becoming dependent takes time and persistence