CAFFEINECAFFEINE

The most widely consumed psychoactive substance in the The most widely consumed psychoactive substance in the world.world.

Caffeine BasicsCaffeine Basics CNS stimulant Alkaloid from a chemical

group called Xanthines Found in 63 species of

plants Everyday 90% of

Americans consume caffeine in some form

MethylxanthinesMethylxanthines

Caffeine (1, 3, 7-trimethylxanthine) – found in coffee, sodas and some OTC medicine

Theophylline (1, 5-dimethylxanthine) – found in tea

Theobromine (3, 7-dimethylxanthine) – found in chocolate

HistoryHistory

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 (History (contcont.).)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 HistoryMore 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 WiredGeneration Wired

‘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 Case of Mountain Mountain

DewDew

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 ContentsCaffeine Contents

7-Up 0 mgRoot Beer (non-Barq’s) 0 mgTea, the elegant option 30-60 mgCoke 45.6 mgMountain Dew 55 mgJOLT 71.2 mg of caffeineCoffee 80-135 mgExcedrin 130 mg per tabletNo Doz 200 mg a pillIn 1998 Americans guzzled 15 billion gallons of sodas, the equivalent of 585 cans for every man woman and child in America.

Profiting SchoolsProfiting 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 soft-drink companies

High-Energy CocktailsHigh-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: Pharmacokinetics: Route of Administration/AbsorptionRoute of Administration/Absorption

Absorption through: Stomach Small intestine Large intestine

Effects of caffeine Depends on:

Food in the body Caffeine in the

substance

Distribution Distribution

Throughout the body and the brain

Water soluble Crosses blood brain

barrier Reaches the fetus No accumulation

within body

More PharmacokineticsMore 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

MetabolismMetabolismThe 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.

Shorter/Faster Metabolism if:

Cigarettes Caucasians Women Child

Longer/SlowerMetabolism if:

Alcohol Asians Men Newborn Liver Damage Pregnant

MetabolismMetabolism

Smoking Will Metabolize Twice as Fast

• Alcohol Will Metabolize Slowly

Metabolism & ExcretionMetabolism & Excretion

Metabolized by liver (first-order kinetics)

• Excreted by kidney via urine (diuretic)

PharmacodynamicsPharmacodynamics 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 ActionMechanisms of Action• Multiple mechanisms

• Adenosine antagonist

- both A1 and A2 sites

• 2nd messenger theory

- Phosphodiesterase inhibition

- cAMP, AMP, intracellular calcium

DosesDoses 50-200 mg

- Sleepy first 5 minutes - Blood levels peak at 30 min. - Stimulant effects

300-1000 mg– 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 IntoxicationDiagnostic Criteria for Caffeine Intoxication

A. Recent consumption of caffeine

B. Five (or more) of the following develop shortly

after caffeine use

restlessness nervousness

excitement insomnia

flushed face diuresis

GI disturbances muscle twitching

rambling flow of speech tachycardia

periods of inexhaustibility psychomotor agitation

Effects on the BodyEffects 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 Effects ((cont’d)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 Behavioral Effects (w/ 100~200 mg)(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

ToleranceTolerance 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

OverdosingOverdosing

Very rare but deadly occurrenceLD50= 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.

WithdrawalWithdrawal

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 incapacitatingOnset: 12-24 hoursPeak: 20-48 hoursDuration: 2-7 days

Withdrawal (cont.)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 WithdrawalSymptoms of WithdrawalThe most commonly reported symptoms of withdrawal are:

• Headache

• Fatigue

• Sleeplessness/Drowsiness

• Difficulty Concentrating

• Work Difficulty

• Irritability

• Depression

• Anxiety

• Flu-like symptoms

• Impairment in psychomotor, vigilance, and cognitive performances

Caffeine AddictionCaffeine 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 UsesMedical 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 EffectsOther Positive Effects

Weight Loss Effects Increased Alertness Enhanced

Concentration Enhance Physical

Endurance and Delay Fatigue

Health ProblemsHealth 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 EffectsOther Negative Effects Diuresis Gastritis Heartburn Lower birth weights Pregnancy risks Panic Attacks Jitters Anxiety Raised Blood Pressure Insomnia

A Dangerous CombinationA 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 Phenylpropanolamine

Adds to the effects of other stimulants– Cocaine, amphetamines, metamphetamines

Generation Wired Generation Wired (cont.)(cont.) 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