Download Caffeinism


most commonly consumed psychoactive drug
in the world
◦ in US – consumed by 80% adult population
◦ found in coffee, tea, cola, chocolate and cocoa
◦ also found in many prescription and OTC
medications
 (FDA estimates ~1000 prescription and 2000 OTC
contain caffeine)
 safe and can be added to just about anything that we can
swallow!
200 mg in 4 ounces!!!!
“


commodity traded most extensively in the
world is oil (wars fought over oil)
Next most widely traded commodity
◦ caffeine
 raw material includes coffee beans, tea leaves, cola
nuts
 estimates ~ 120,000 tons/year; employs more than
20,000,000 people



Chinese claim to have discovered tea around
2700 BCE
At least ½ the world drinks tea
England and China – fed each others
addictions
◦ China provided tea for England and England (from
their British Colonies close to India) provided China
with Opium
Cutty Sark - renovated Tea- clipper
last survivor - mid 1800’s
now in Greenwich England
called “Clipper ships” very fast sailing ships built to cut
the time needed to get tea from
India and China back to Europe

absorption – oral caffeine is rapidly and
completely absorbed
◦ significant blood levels within 30 – 45 min;
completely absorption over next 90 min
◦ freely and equally distributed throughout the body
◦ crosses placenta to fetus
 breast milk = or exceeds level in maternal plasma
Pharmacokinetics:
 Half-life is ~3.5–5 hour in adult humans,
but 60–100 hours in infants.

Half-life is reduced by 30–50 percent in
smokers; doubled in women on oral
contraceptives (and prolonged during last
trimester of pregnancy).

metabolized by liver before excretion
◦ main metabolites; theophylline, theobromine
◦ CYP1A2 enzyme
 certain SSRI antidepressants (flovoxamine) are potent
CYP1A2 inhibitors – caution needed…..
Tolerance:
Some effects that became tolerant in humans:
◦ Blood pressure, heart rate
◦ Adrenalin, noradrenalin levels
◦ Anxiety, nervousness, energy
Tolerance:
Some effects that did not show tolerance:
◦ Caffeine-induced alertness and wakefulness
◦ Cerebral energy metabolism
Sleep is the physiological function most sensitive
to the effects of caffeine.
◦ Caffeine increases the time it takes to go to sleep
and the total duration, but does not disturb the
phases.
◦ Some tolerance develops to sleep disturbance.
EFFECT OF AN
ADENOSINE
ANTAGONIST
(CAFFEINE) ON
SLEEP IN A
NORMAL SUBJECT
Reinforcement:
not a powerful reinforcer in animals selfadministering intravenously.
Reinforcement varies with dose –


◦
does not directly increase DA in mesolimbic regions –
maybe prefrontal cortex
Discrimination

Human subjects can discriminate caffeine from
placebo, in coffee or capsules

Doses of 300 mg or more are most reliably
detected, but some people can detect much
lower doses


ingestion of 85 – 250 mg caffeine (1 -3 cups
of coffee) increases capacity for sustained
attention and decreased reaction time
fine or delicate muscular coordination or
timing…..

600-750mg a day of caffeine probably will
NOT make someone feel very well
Toxicity:



Caffeinism – (typically above 1000 mg/kg
6 deaths in humans; lethal dose estimated at 10
grams taken orally (about 100 cups of coffee); death
is due to convulsions and respiratory collapse.
Is caffeine safe in pregnancy?
◦ Controversial
3 types of related alkaloids from plants
1.
2.
3.
theophylline
caffeine
theobromine
1.
2.
relax smooth muscle (notably bronchial
muscles)
stimulate CNS and cardiac muscle
•
3.
theophylline and caffeine more than theobromine
produce diuresis in kidneys

therapeutically- used to treat a variety of
disorders
◦ asthma (theophylline mostly to relax
respiratory
muscles)
◦ narcolepsy (to maintain daytime wakefulness)
◦ migraine
◦ adjunct to treat headache and other pain
syndromes

Caffeine – effective psychostimulant

heavy consumption (12 or more cups/day or
1.5 g caffeine)
◦ agitation, anxiety, tremors, rapid breathing,
insomnia


lethal dose – 10 g (100 cups of coffee)
people with anxiety disorders – especially
sensitive to caffeine



anxiety disorders
tremors
possible dehydration

caffeine exerts variety of effects in CNS at
different doses
◦ most likely – blockade of adenosine receptors
◦ so adenosine antagonist!
◦ represents major site of action

Adenosine –
◦ neuromodulator of several nt in CNS
◦ majority of adenosine effects are sedating,
depressing, and anticonvulsant