CAFFEINE
The most widely consumed psychoactive substance in the
world.
Caffeine Basics
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
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CNS stimulant
Alkaloid from a chemical
group called Xanthines
Found in 63 species of
plants
Everyday 90% of
Americans consume
caffeine in some form
Methylxanthines

Caffeine (1, 3, 7trimethylxanthine) –
found in coffee, sodas and
some OTC medicine

Theophylline (1, 5dimethylxanthine) –
found in tea

Theobromine (3, 7dimethylxanthine) –
found in chocolate
History

Plants evolve caffeine to
protect themselves from attack
by bacteria, fungi and insects.
 1st use of caffeine as early as 600,000
BCE
 First historical record of caffeine use
from Aztec records.
 Homer makes reference to a
mysterious black bitter beverage with
the power to ward off sleep.
History (cont.)
1475 - The worlds first coffee
shop opens in
Constantinople
1821 - Pure caffeine extracted
from coffee
1880's - Caffeinated soft drinks
appear
1903 - Researchers remove
caffeine from beans ‘without
destroying the flavor’
1923 - Decaffeinated coffee is
introduced to the United
States
More History
1940 - The US imports 70
percent of the world coffee
crop.
1962 - American per-capita
coffee consumption peaks at
more than three cups a day.
1971 - First Starbucks opens in
Seattle.
1995 - Coffee becomes the
worlds most popular
beverage (overtaking tea).
Generation Wired
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‘Tweenagers’ consisting of 8 to 14 year olds are
heavily targeted by marketers
Why do so many young tweenagers drink
caffeinated beverages?
– Coffee bars are often the only place for young
people to hang out
– Marketing of ‘cold-sweet’ coffee drinks and
high caffeine sports/energy drinks
Case of
Mountain
Dew


In Canada, adding caffeine to citrus drinks
has not been allowed. The company that
produces Mountain Dew has been fighting
to add caffeine to Canadian Mountain Dew
claiming to improve taste.
The Do the Dew ad campaign shows
frenzied lifestyle
Caffeine Contents
7-Up
0 mg
Root Beer (non-Barq’s)
0 mg
Tea, the elegant option
30-60 mg
Coke
45.6 mg
Mountain Dew
55 mg
JOLT
71.2 mg of caffeine
Coffee
80-135 mg
Excedrin
130 mg per tablet
No Doz
200 mg a pill
In 1998 Americans guzzled 15 billion gallons of
sodas, the equivalent of 585 cans for every man
woman and child in America.
Profiting Schools

Soda companies pay school districts for
exclusive selling rights (Coke vs Pepsi)
and for the right to put ads on the gym
walls and school buses
– 1997 in West Virginia a state law
prohibiting the sale of soda in schools was
overturned after extensive lobbying by softdrink companies
High-Energy Cocktails

mixture of energy drinks
and alcohol sold as
expensive cocktails in
many clubs
– 100mg of caffeine -often sold without
labels
– Dangerous when
combined with alcohol
Anheuser-Busch’s ‘BE’ Takes
Beer to a New Level
ST. LOUIS (Oct. 4, 2004) –
B-to-the-E (BE), Budweiser's newest
entry in a long line of innovative beers
by Anheuser-Busch, is a distinctive
new product for contemporary adults
who are looking for the latest beverage
to keep up with their highly social and
fast-paced lifestyles.
54 mg of caffeine (plus guarana and
ginseng)
Pharmacokinetics:
Route of Administration/Absorption
Absorption through:
 Stomach
 Small intestine
 Large intestine
Effects of caffeine
Depends on:
 Food in the body
 Caffeine in the
substance
Distribution
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Throughout the
body and the brain
Water soluble
Crosses blood brain
barrier
Reaches the fetus
No accumulation
within body
More Pharmacokinetics
Dose: 100 mg = 1 Cup of
Arabica Coffee (8oz)
Route: Taken Orally
Onset: 30-60 Minutes
Peak At: 2 Hours
Half-life: Approximately 3-7
hours
Metabolism
The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.
One form of the enzyme, produced by the gene variant 1A, metabolizes caffeine
rapidly while another form, 1F, metabolizes it slowly.
Longer/Slower
Metabolism if:
 Alcohol
 Asians
 Men
 Newborn
 Liver Damage
 Pregnant
Shorter/Faster
Metabolism if:
 Cigarettes
 Caucasians
 Women
 Child
Metabolism

Smoking Will Metabolize Twice as Fast
• Alcohol Will Metabolize Slowly
Metabolism & Excretion

Metabolized by liver (first-order kinetics)
• Excreted by kidney via urine (diuretic)
Pharmacodynamics

Main mechanism of action: direct competitive antagonist of
adenosine receptors - A1 and A2a

Effects on Monoamines:
-Elevates levels of 5-HT in the brain
-Stimulates NE neurons
-Increases rate of DA formation
→However, this may be quickly followed by a
decrease
→Yet, injection of caffeine usually increases
locomotor activity, an effect supposedly blocked
by a DA receptor antagonist
Mechanisms of Action
•
Multiple mechanisms
•
Adenosine antagonist
- both A1 and A2 sites
•
2nd messenger theory
- Phosphodiesterase inhibition
- cAMP, AMP, intracellular
calcium
Doses

50-200 mg
- Sleepy first 5 minutes
- Blood levels peak at 30 min.
- Stimulant effects

300-1000 mg
–
–
–
–
–
–
–
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Prolonged ability to perform
Exaggeration of side effects
Pronounced insomnia
Nervousness
Irritability
Tremor
Restlessness
1000+ mg
–
–
–
–
“Caffeinism”
All of the above worsen
GI disturbances
Cardiac arrhythmias
Diagnostic Criteria for Caffeine Intoxication
A. Recent consumption of caffeine
B. Five (or more) of the following develop shortly
after caffeine use
restlessness
nervousness
excitement
flushed face
GI disturbances
rambling flow of speech
periods of inexhaustibility
insomnia
diuresis
muscle twitching
tachycardia
psychomotor agitation
Effects on the Body
• Central Nervous System
- stimulant
• Autonomic Nervous System
- change in EMG activity
• Cardiovascular System
- heart and blood vessels
- blood platelets
• Gastrointestinal System
- cause for ulcers?
• Respiratory
- increases blood and air to lungs
Effects (cont’d)
• Skeletal Muscles
- contraction (contrarily)
• Energy Metabolism
- basal metabolic rate, free fatty
acids, oxidation of fats in
exercise
• Neurotransmitters
- norepinephrine in CNS,
norepinephrine and epinephrine
in blood, seratonin in brain
• Neuroendicrine effects
- stress (high doses)
Behavioral Effects (w/ 100~200 mg)

Increases wakefulness, alleviates
fatigue, facilitates concentration

Can also produce: elevated mood,
shaky/jittery feeling

↑ time to fall asleep,↓ amount
and quality of sleep

↑ attention/vigilance, ability to
sustain performance

↑ work capacity/speed,↓ # of errors
Fig. 3-d: Percent change on a repeated
acquisition test, which assesses motor learning
and memory
Tolerance
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Decreased A2a receptor expression
Increased A1 receptor expression
Tolerance to respiratory effects after 8
consecutive days of daily administration
Cross-tolerance
Caffeine tolerance is pharmacodynamic
Overdosing
Very rare but deadly occurrence
 LD50= 150mg/kg

– 70 kg (154 lbs) person’s lethal dose is 10.5
grams
– In 1986, of 2709 cases of caffeine
“exposure” registered with Poison Control
Centers, 0.1% or 3 cases resulted in death.
Withdrawal
Withdrawal has been reported after
stopping a dose as low as 100 mg/day
 40-70% of people who attempt to quit
caffeine experience withdrawal
 Withdrawal can be totally incapacitating
 Onset: 12-24 hours
 Peak: 20-48 hours
 Duration: 2-7 days

Withdrawal (cont.)

Withdrawal can occur by
abstaining from a dose as
low as 100mg/day
– equivalent to a cup of coffee or
2-3 caffeinated soft drinks.

Telephone survey shows
40-70% of consumers trying
to quit reported experiencing
withdrawal symptoms
Symptoms of Withdrawal
The most commonly reported symptoms of withdrawal are:
• Headache
• Irritability
• Fatigue
• Depression
• Sleeplessness/Drowsiness
• Anxiety
• Difficulty Concentrating
• Flu-like symptoms
• Work Difficulty
• Impairment in
psychomotor,
vigilance, and
cognitive
performances
Caffeine Addiction

Not included in DSM IV
– While caffeine produces physical
dependence, there is insufficient
information on whether it causes inability to
stop use or cause use despite harm.
Medical Uses

Treatment of migraine headaches, caused
by dilation of blood vessels
– Mixed with ergotamine tartrate (vasoconstrictor)
– Increases the power of aspirin and other
painkillers by about 40%
– has also been used to treat:
• chronic obstructive pulmonary disease
• asthma
• breathing problems in newborns
• overdoses with opioid drugs
Other Positive Effects

Weight Loss Effects
 Increased Alertness
 Enhanced
Concentration
 Enhance Physical
Endurance and
Delay Fatigue
Health Problems

5 or more cups of coffee daily can increase the
risk of heart disease due to:
- ↑ heart rate
- ↑ blood pressure
- ↑ blood cholesterol levels

Drinking coffee may cause increase of stress
hormones
- adrenal gland produces adrenaline until no more can
be produced
- leads to chronic fatigue, constant exhaustion and
susceptibility to disease
Other Negative Effects

Diuresis
 Gastritis
 Heartburn
 Lower birth weights
 Pregnancy risks
 Panic Attacks
 Jitters
 Anxiety
 Raised Blood Pressure
 Insomnia
A Dangerous Combination

Because of risk of increased blood pressure,
caffeine should be used cautiously by
patients who take other drugs that raise bp
– Anti-Depressants that are MAO inhibitors

Marplan, Nardil, and Parnate
– High doses of cold medicine
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Phenylpropanolamine
Adds to the effects of other stimulants
– Cocaine, amphetamines, metamphetamines
Generation Wired (cont.)
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Sodas are aggressively marketed for
kids
Marketers focus on children starting at
the age of 18 months
In order to establish consumer loyalty
to their brand, advertisers try to appeal
to younger and younger customers
– Mountain Dew, the preferred soda of
children under 6, distributed a half million
free pagers to children in 1998 in an ad
campaign