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1. Chapter 6
Stimulants
© 2011 McGraw-Hill Higher Education. All rights reserved.

2. Stimulants
 Stimulants are substances
that keep a person going
mentally and physically
 Cocaine and amphetamine
are restricted stimulants
 Caffeine and nicotine are
readily available stimulants
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3. History of Cocaine
 Coca is a bush that grows in the Andes and
produces cocaine
 Coca has been harvested for thousands of years
and actively cultivated for over 800 years
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4. History of Cocaine
 Natives of the Andes chewed
coca leaves to give them
greater strength and
endurance
 The coca leaf was an
important part of Inca culture
 Used in religious ceremonies
and as currency
Coca leaf market
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5. History of Cocaine
 Coca wine: Angelo Mariani
 Used coca leaf extract in many
products including lozenges,
tea, and, especially, wine
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6. History of Cocaine
 Coca extract was later used in the United States in early
versions of Coca-Cola and in many patent medicines
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7. History of Cocaine
 Local anesthesia: Dr. W. S. Halsted
 Experimented with ability of cocaine to produce
local anesthesia
 Delivered via newly developed hypodermic syringe
 Cocaine was isolated
before 1860
 Processing 500 kilograms
of coca leaves yields
1 kilogram of cocaine
Drying coca leaves
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8. History of Cocaine
 Early psychiatric uses:
Sigmund Freud
 Studied use of cocaine as a treatment for
depression and morphine dependence
 Later opposed use of the drug after nursing
a friend through cocaine psychosis
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9. Early Legal Control
 46 states passed laws to regulate cocaine
between 1887 and 1914
 Press and politicians made unsubstantiated
claims about cocaine use among southern
blacks:
 Widespread
 Associated with increased violent crime
 Negative publicity about cocaine influenced
the passage of the 1914 Harrison Act
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10. Forms of Cocaine
 Coca paste
 Crude extract created during the
manufacture of cocaine
 Can be mixed with tobacco and
smoked
 Cocaine hydrochloride
 Most common form of pure
cocaine
 Stable water-soluble salt
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11. Forms of Cocaine
 Freebase
 Prepared as a chemical
base
 Can be heated and the
vapors inhaled
 Crack or rock
 Lumps of dried,
smokable cocaine
 Prepared by mixing
cocaine with water and
baking soda
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12. Contemporary Legal
Controls on Cocaine
 Cocaine use began to increase again at the end
of the 1960s
 Prior to 1985, the major form of the drug available
was cocaine hydrochloride, which was snorted
 Cocaine was relatively expensive and its use was
associated with status, wealth, and fame
 Then an inexpensive ($5 to $10 a hit) form of
smokable cocaine became available—crack
 Smoked cocaine has a greater abuse potential than
snorted cocaine
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13. Contemporary Legal
Controls on Cocaine
 Media and politicians focused on crack use
among urban blacks
 Associated with violence and dependency
 Anti-Drug Abuse Acts of 1986 and 1988
 Penalties for sale of crack cocaine significantly more
severe than penalties associated with powder cocaine
 Tougher penalties for first-time users of crack
 Concerns about federal cocaine sentencing policy
 Does it overstate the seriousness of most crack
cocaine offenses?
 Does it disproportionately affect the black community?
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14. Mechanism of Action
 Chemical structure does not tell us how or why cocaine
affects the brain
 Cocaine blocks reuptake of dopamine, serotonin, and
norepinephrine
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15. Cocaine Administration
 Chewing or sucking coca leaves
 Slow absorption and onset of effects
 “Snorting” through nasal mucous
membranes
 Rapid absorption and onset of effects
 Injected intravenously
 Rapid and brief effects
 Smoked
 Rapid and brief effects
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16. Cocaine Elimination
 Cocaine is metabolized by enzymes in the
blood and liver
 Cocaine has a half-life of about one hour
 Major metabolites (detected by drug
screens) have a half-life of eight hours
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17. Potential Beneficial Uses
 Local anesthetic properties of cocaine were
discovered in 1860, but the drug was not
used medically until 1884
 Synthesized drugs have largely replaced
cocaine for medical use
 Cocaine remains in use for surgery in the
nasal, laryngeal, and esophageal regions
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18. Causes for Concern:
Acute Toxicity
 Acute cocaine toxicity causes profound CNS
stimulation, which can lead to respiratory or
cardiac arrest
 Significant individual variation in the uptake and
metabolism of cocaine
 Difficult to estimate the size of a lethal dose
 Rare, severe, and unpredictable reactions can
cause cardiac failure
 Cocaine combined with alcohol can cause the
formation of the toxic chemical cocaethylene
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19. Causes for Concern:
Chronic Toxicity
 Risks of regularly
snorting cocaine
 Damage to the nasal
septum
 Paranoid psychosis
 Damage to the heart
muscle
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20. Causes for Concern:
Chronic Toxicity
 Dependence occurs in some users
 Animal and human studies have shown that
cocaine is a powerfully reinforcing drug
 Some people experience withdrawal
symptoms
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21. Causes for Concern
 Cocaine use during
pregnancy
 Increased risk of
miscarriage and torn
placenta
 Long-term effects of
prenatal cocaine
exposure still under
study
Infant exposed to
cocaine being monitored
in ICU
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22. Supply of Illicit Cocaine
 Readily available in all
major U.S. cities
 Street cocaine averages
about 50-75 percent pure
 Most illicit cocaine comes
from Peru, Bolivia, and
Columbia
Seized cocaine
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23. Cocaine: Current Use and
Future Trends
 2006 surveys indicate that about 2 percent
of adults currently use cocaine
 Down from a high of 7 to 9 percent in the 1980s
 Usage rates of cocaine and amphetamine
tend to cycle in opposition to each other
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24. Amphetamines:
History
 The Chinese used a
medicinal tea made from
ma huang (Ephedra)
 Active ingredient = ephedrine
 Ephedrine is a
sympathomimetic drug
 Stimulates the sympathetic
branch of the autonomic
nervous system
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25. Amphetamines:
History
 New synthesized chemical similar to ephedrine,
called amphetamine, was patented in 1932
 Amphetamine was used medically
 Asthma
 Narcolepsy
 Hyperactivity in children
 Appetite suppressant
 Stimulant
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26. Amphetamines:
History
 Use by soldiers in World War II to fight fatigue
 1960s
 Amphetamine + heroin injected together = speedball
 Most street amphetamines came from prescriptions
 “Speed scene” = a time and place in which people used
and became dependent on intravenous amphetamine
 Amphetamines became more tightly controlled
 Many look-alikes appeared
 Some users switched back to cocaine
 Illicit manufacture of methamphetamine grew
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27. Amphetamines:
History
 Limited amphetamine
availability increased
the number of illicit
laboratories making
methamphetamine
 Manufacture of
methamphetamine is
dangerous and
associated with toxic
fumes and residue Materials from a garage meth lab
© 2011 McGraw-Hill Higher Education. All rights reserved.

28. Amphetamines:
History
 Methamphetamine
hydrochloride crystals
 Ice or crystal meth
 Smokable
 Methamphetamine abuse
began in the western
United States and then
spread east; it is also now
considered a “club drug”
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29. Amphetamine
Pharmacology
 Chemical structure of amphetamine is similar to
the catecholamine neurotransmitters
 The structure of methamphetamine allows it to
more easily cross the blood-brain barrier
 Ephedrine and PPA are less able to cross the barrier
and so produce more peripheral than central nervous
system effects
 Causes increased activity of monoamine
neurotransmitters (dopamine, norepinephrine,
serotonin) by stimulating their release
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30. Molecular Structure
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31. Amphetamine
Absorption and Elimination
 Peak effects
 1.5 hours after oral ingestion
 5-20 minutes after intranasal administration
 5-10 minutes following intravenous injection or
smoking
 Half-life
 5-12 hours
 Rapid tolerance (tachyphylaxis) can occur
after high doses
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32. Beneficial Uses
 Previous use for depression to temporarily elevate
mood
 Adjunctive therapy- a treatment used together with primary
treatment.
 The benefit of amphetamines is that their effects occur rapidly
compared with standard antidepressant medications.
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33. Beneficial Uses
 Weight control
 Widely use to reduce food intake and body
weight
 Effect is real but small
 Combination of fenfluramine and phentermine
was associated with heart valve damage and
lung disease in some people
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34. Beneficial Uses
 Narcolepsy (uncontrolled daytime
episodes of muscular weakness and falling
asleep)
 Stimulants used to keep patients awake during
the day
 Newer drug modafinil (Provigil) promotes
wakefulness by increasing the activity of
norepinephrine and dopamine
 Low abuse potential
 Doesn’t induce tolerance
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35. Beneficial Uses
 Treatment of attention-deficit
hyperactivity disorder (ADHD)
 Characterized by problems with
inattention, hyperactivity, and
impulsivity
 Stimulant medications can reverse
catecholamine-associated deficits
that may underlie ADHD
 Due to side effects and concerns
about the risk of abuse, other
treatments for ADHD are being
studied
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36. Beneficial Uses
 “Smart pills”
 At a low level of arousal, may improve
performance
 At a high level of arousal, may decrease
performance, especially on complex or difficult
tasks that require concentration
 Athletics
 Under some circumstances, may produce slight
improvements in athletic performance
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37. Effects of Stimulants on
Performance
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38. Acute Toxicity
 Acute behavioral toxicity
 Increases in feelings of power, suspicion,
paranoia
 Potential risk of violent behavior
 Very high doses may destroy
catecholamine neurons
 Contaminants formed during the
manufacture of illicit methamphetamine
may have toxic effects on brain cells
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39. Chronic Toxicity from
High-Dose Use
 Paranoid psychosis
 Two possible reasons for the psychosis
 Heavy methamphetamine users have schizoid
personalities.
 Caused by sleep deprevation.
 Higher risk among those who inject the drug
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40. Dependence Potential of
Amphetamines
 Often no obvious withdrawal symptoms
 Produce psychological dependence
 Capable of producing dependence as
defined by DSM criteria
 A potent reinforcer
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41. Chapter 6
Stimulants
© 2011 McGraw-Hill Higher Education. All rights reserved.