Chapter 13
Opioids
Opioids
 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
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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 engaged 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)
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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 Sertürner
extracted 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 middleaged, 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
 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
 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
 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
 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-aday 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.
 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)
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
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.
 Synthetics
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Methadone
Meperidine
Oxycodone
Oxymorphone
Hydrocodone
Hydromorphone
Dihydrocodeine
Propoxyphene
Pentazocine
Fentanyl
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
Signs
Heroin or
Morphine
Methadone
Craving for drugs, anxiety
6
24
Yawning, perspiration, running nose, teary eyes
14
34-48
Increase in above signs plus pupil dilation, goose bumps,
tremors, hot and cold flashes, aching bones and
muscles, loss of appetite
16
48-72
Increased intensity of above, plus insomnia; raised blood
pressure; increased temperature, pulse rate, respiratory
rate and depth; restlessness; nausea
24-36
Increased intensity of above, plus curled-up position,
vomiting, diarrhea, weight loss, spontaneous ejaculation
or orgasm, hemoconcentration, increased blood sugar
36-48
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
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Misconceptions
 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
(END OF PRESENTATION)
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