The World’s Most Popular Drug
Christopher Ryan
Emeral Diaz
Hitesh Bhakta
Jacob Salmon
Introduction
• For this presentation, we wanted the opportunity to
research a drug that most people are familiar with and
consume every single day.
• It is one of the world’s most popular psychoactive
drugs and is found in many different forms.
• This drug is a stimulant; it is potentially addicting,
and can cause withdrawal symptoms.
Can you guess, which drug this
is?
Caffeine
• The objective of this presentation is to provide little
known facts about caffeine, discuss the importance,
and outline the effects of the drug once it enters our
body.
American Caffeine Consumption
Each year Americans consume 45 millions pounds of caffeine.
• On average each person consumes 2.6 cups of coffee a day
or 363.5 mg of caffeine.
• In the US, more than 80% of adults consume caffeine on a
daily basis.
o Among individuals that do not drink caffeine the average
intake is still ~91mg/day
• Over 450,000,000 cups of coffee are consumed in the USA
every day!
4
Fast Facts about Caffeine
• Each year 120,000 tons of caffeine are consumed.
• The average daily consumption of caffeine among adults is 200
mg/day.
• Women metabolize caffeine about 25% faster than men.
• Contrary to popular belief, caffeine (or coffee) won't help someone
sober up if they have had too much to drink
History of Caffeine
• Responsible for the modern world.
• It became popular in Europe at the start of the industrial
revolution, and served as a substitution for beer.
• Humans were forced to adapt as the job force switched from
farming to industrial (indoor) jobs
o Artificial light and caffeine became the way to adjust to
new types of jobs; workdays were no longer regulated by
just sunlight.
• It was believed that disease incidence would decrease due to
the boiling of water for coffee or tea.
Caffeine Today
• Reasons for using caffeine are very similar to those of the past.
• It is still used as a way to increase alertness.
• And in addition it is used to improve memory, stimulate the body,
and enhance one’s mood.
• ** Especially for us college students! **
Where is Caffeine found?
• Harvested from plants but can be synthetically made.
• Not only found in coffee and energy drinks, but also in some
unlikely places like:
o chocolate, gum, and migraine medicine.
• Concentration can vary depending on the source, where it
comes from, and how it is made. (Table 1)
Table 1: Caffeine Content in a Variety of Sources.
Serving Size (fl. oz)
Caffeine content per Serving
(mg)
Coffee (Brewed)
5
40-180
Decaf Coffee
5
2-5
Starbucks Coffee Grande
16
330
Espresso
1
64
Tea
5
24-50
Coca Cola Classic
12
35
Diet Coke
12
47
Mountain Dew
12
54
Pepsi
12
38
Diet Pepsi
12
35
Red Bull
8.3
80
Rockstar
8
80
Full Throttle
8
72
Hershey's Chocolate Bar
1.55 oz
9
Excedrin, Extra Strength
2 tablets
130
NoDoz Maximum Strength
1 tablet
200
Jolt Caffeinated Gum
1 stick
35
Caffeine Chemistry
Molecular Formula:
C8H10N4O2
Molecular Weight : 194.19
Medically known as
trimethylxanthine.
Figure 1: Caffeine Structure
Absorption
• Absorption from the GI tract takes approximately 45 minutes
while peak plasma plasma concentration peaks 15 to 120 min
after consumption
• Caffeine can pass through all types of membranes because it
is hydrophobic in nature
• There is no blood-brain or blood-placental barrier.
o Cause of premature birth weight in infants
Metabolism
• Takes place in the liver with help from Cytochrome P450,
where it is metabolized into three seperate substances
Figure 2: Caffeine derivatives
Metabolism
• Paraxanthine: Increases lipolysis, leading to elevated
glycerol and free fatty acid levels in the blood plasma. Also
increases the amounts of Ca++ in the skeletal muscle
• Theobromine: Dilates blood vessels and mildly increases
urine production.
• Theophylline: Relaxes smooth muscles of the bronchi, and
is used to treat asthma.Can cause nausea and irregular
heartbeat
Each of these metabolites is further metabolized and then
excreted in the urine.
Figure 1: Metabolism of Caffeine
Caffeine and Adenosine: a battle over
receptor sites.
• Adenosine is the primary sleep mechanism and
causes drowsiness because it slows neural cell
activity.
• Caffeine increases alertness by binding to
adenosine receptors in the brain, inhibiting the
normal response.
Mechanism of Action
• Primarily stimulates the CNS.
• Tolerance to caffeine is associated with increased adenosine
receptor activity and a shifting of A1 receptors to a high
affinity state
• Phosphodiesterase inhibition - this enzyme is responsible for
the breakdown of cAMP and therefore this action of the
methylxanthines leads to increased cAMP
Mechanism of Action
• 2nd messenger functions.Action at Ca++ channels to increase
entry of Ca++ into cells and to decrease sarcolemma sequestration
of Ca++.
• This may be related to the weak positive inotropic effect of the
drug at high dose rates. Binding to GABA receptors at the
benzodiazepine site.
Half-life
• Humans: 2.5-5.7 hours.
o The same study showed that individuals with a compromised
liver have an extended half life.
o During neonatal development half-life increases to 100 hours
due to decreased activity of cytochrome P-450.
• Rats/Mouse: 0.7- 1.2 hours
• Monkey: 3-5 hours
Overdose LD50
• X>300 milligrams per kilogram of body mass
o Dependent on body weight/tolerance
o To Receive a lethal overdose is hard to achieve; however
with caffeine pills it becomes very easy.
o If consumed little as 3-20 grams you can be hospitalized. In
short amount of time.
• Death resulting from Ventricular Fibrillation, due to the effect
of caffeine on the cardiovascular system.
1,2,3
Side Effects
Toxicity
• Pregnancy
o Consuming over 200mg per/day significantly increases the
rate of miscarriage.
• Children
o Stunts Growth
• Memory (Low Dose in mice)
o Slows development of hippocampus-dependent learning
and impaired long-term memory in mice
 Via inhibition of hippocampal neurogenesis.
1,2
Minor Overdose Effects
• Excess of 300 milligrams (dependent on body
weight/tolerance)
• Causes over-stimulation in Central Nervous System
• Common Problems
o restlessness, nervousness, excitement, insomnia, flushing
of the face, increased urination, gastrointestinal
disturbance, muscle twitching, a rambling flow of thought
and speech, irritability, irregular or rapid heart beat, and
psycho motor agitation.
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Major Overdose Effects
•
•
•
•
•
•
•
•
Mania
Depression
Lapses in judgment
Disorientation
Disinhibition
Delusions
Hallucinations and psychosis may occur
Rhabdomyolysis (breakdown of skeletal muscle tissue) can
be provoked.
• Lethal intoxication when blood concentration = 500 mM
caffeine
Interactions with Ethanol
• Mechanism of Coffee's "sobering" effects.
Ethanol consumption causes an increase in adenosine
levels which makes you feel tired.
o The vasoconstricting properties of caffeine prevent the
extra adenosine from binding to its receptors, combined
with the competitive binding of caffeine to those same
binding sites leads to the reduced sensation of fatigue that
is so often reported.
o
Interactions with NicotineDo smokers really drink more
coffee?
• Smokers on average drink 50% more coffee, than
non-smokers.
• Smokers actually metabolize caffeine approximately
50% faster as well.
o
Ex-smokers also metabolize caffeine at a faster rate, but its exact
mechanism is not fully understood.
• Drinking coffee also increases the number of
cigarretes smoked, especially during periods of the
day that have increased coffee consumption.
Caffeine and Cancer
• A study by the Proceedings of the National Academy
of Sciences: found that a moderate amount of
exercise and caffeine in mice
• Decreases the risk of skin cancer because the rate of
apoptosis is increased in cells damaged by UV rays
•
• The study also found, that the amount of fat in these
organisms was significantly decreased more than just
running or drinking caffeine separately.
Animal Studies
Caffeine in Spiders
When Exposed:
•Webs varied in size, length of
thread, organization, density and
structure.
•Excess caffeine caused issues
with proper techniques in
construction of webs
Animal Studies
Caffeine in Mice:
Caffeine was added to the dendritic spines of mice via In Vitro
methodolgy. Resulting in growth by 33% and formed new stems,
later returning to their original sizes.
In another study:
-100 milligrams of caffeine increased the size of the frontal lobe
(memory) and the anterior cingulated cortex (attention)
-The caffeinated subjects did perform better with memory task
1
Benefits of Caffeine
Parkinson's disease
 Researchers from the Harvard School of Public Health in Boston
have concluded that regular caffeine consumption leads to a lower risk
of developing Parkinson’s by up to 80%.
 Caffeine reduces the amount of neurotransmitters produced by the
brain, which may cause damage to surrounding brain tissue.
Gallstones
 Those who drink two to three cups of regular coffee a day have
about a 20 percent lower risk of gallstones than non-drinkers.
o Caffeine may stimulate the gallbladder to contract, emptying stoneforming cholesterol and bile
Benefits of Caffeine
Mental Performance
•
Improves alertness and reaction time
•
Stimulates the central system as it simultaneously lowers blood
sugar and increases the brain's demand for sugar. Resulting in a
temporary lift.
Mood
•
Increase in positive mood including an increased state of wellbeing, happiness, energy, arousal, alertness, and sociability.
Physical Performance
• Caffeine helps the body burn fat instead of carbohydrates, and it
lowers levels of perceived pain.
•
Improvements in aerobic physical endurance and anaerobic
performance.
Benefits
Headache
 During a headache blood vessels dialate, but caffeine causes
blood vessels to constrict relieving the pain.
 It is a mild analgesic.
 Helps the body absorb headache medications more quickly.
 Can makes pain relievers more effective by upregulating
them.
Heart Health
 Coffee is full of antioxidants.
 Moderate coffee intake can help prevent some
cardiovascular problems.
 Women who drink two to three cups of coffee a day have a
25% lower risk of heart disease and an 18% lower risk of
developing diseases other than cancer than non-coffee drink
Cost:
Sleep

Insomnia is common when taken before bed.
Disease risk

Inhibits the absorption of iron and calcium from food,
leading to an increased risk for development of
osteoporosis.(Journal of AMA; JAMA, 26 Jan. 1994, p. 280-3.)

Increased susceptibility to rheumatoid arthritis.
o Correlation between coffee consumption and a biochemical
marker for rheumatism.
o Those who consume four cups daily are twice as likely to test
positive for arthritis.
Cost:
Dehydration
 Caffeine has a mild diuretic effect, increasing the possibility
of dehydration during exercise.
Reduced flow of blood to the brain from 10% to 20%
Withdrawal symptoms can occur after regular consumption of
just a single cup per day.

Reproduction

Caffeine reduces rates of sperm motility.

High levels of caffeine intake may delay conception
among fertile women. (Am J Epidemiol1997; 145: 324–34.)
Results and Discussion
• Caffeine use is wide spread.
• Effects in humans differ depending on body composition,
metabolism rates, and stage of development
• Found in many common products that are consumed
everyday (making acute overdoses easy to come by)
• Has both rewards and costs to user
• Socially acceptable in most cultures.
Summary and Conclusions
•Caffeine in moderation is helpful to the human body;
however
•
•Caffeine has the ability to reduce the chances of
Parkinson's disease with moderate use.
•
• short term memory is increased momentarily.
Summary and Conclusions
•Caffeine addiction is real and can cause serious and
detrimental effects on ones health.
•Over consumption and disregard for the bodies limitations
can effectively result in damage to vital organs as well as long
term kidney damage.
•Can result in long-term memory loss and in the inability to
think creatively.
Summary and Conclusions
•Caffeine is one of the most widely utilized drugs in the
world.
Rewards include:
Alertness
Prolonged Susceptibility to sleep
Some Studies Show Increased performance
Costs Include:
Anxiety
Irretability
Restlessness
Summary and Conclusion
Tolerance:
• SOME people develop tolerances to caffeine in certain
aspects
• Over time, a person can become acclimated to the initial
increase in blood pressure associated with occasional
caffeine use.
• Or Opposite desired effect (tiredness) arises.
Withdrawal effects:
• Some characteristics of physical drug dependance with
long term use
• Urge to re-administer not as strong as other addictive
stimulants
• Does not appear to be a major issue
Summary and Conclusions
Possible new hypothesis to test:
• Long term effects of caffeine in combination with
supplements found in energy drinks
• Increasing risk of caffeine overdoses due to the trends of
rising concentrations and availability of caffeinated
products.
• Caffeine's effect on memory in college students and their
study habits.
Dealing With a Caffeine Overdose
• Immediately Call National Poison Control Center at 1-800222-1222.
• Do NOT make the person throw up unless told to do so by
poison control or a doctor.
• In an emergency room, as treatment, expect
o Activated charcoal
o Laxative
o Tube through the nose into the stomach to wash out the
stomach (gastric lavage)
• Always use caffeine containing products in moderation and
remember everything is toxic!
5
References
1. Lesk VE, Womble SP. (2004). "Caffeine, priming, and tip of the tongue:
evidence for plasticity in the phonological system". Behavioral
Neuroscience. 118 (2): 453–61. doi:10.1037/0735-7044.118.3.453. PMID
15174922.
2. ^ Han ME, Park KH, Baek SY, et al (May 2007). "Inhibitory effects of
caffeine on hippocampal neurogenesis and function". Biochem. Biophys.
Res. Commun. 356 (4): 976–80. doi:10.1016/j.bbrc.2007.03.086. PMID
17400186.
3. ^ Kamijo, Y; Soma K, Asari Y, Ohwada T (December 1999). "Severe
rhabdomyolysis following massive ingestion of oolong tea: caffeine
intoxication with coexisting hyponatremia". Veterinary and Human
Toxicology 41 (6): 381–3. doi:10.1152/physrev.00004.2004. PMID
10592946.
References Continued
4. Schreiber et al., Measurement of coffee and caffeine intake:
Implications for epidemiolgic research, Preventive Medicine, 17:280294, 1988 and Chou, T., Wake up and smell the coffee. Caffeine,
coffee and the medical consequences, West. J. Med., 157:544-553,
1992
5. http://health.nytimes.com/health/guides/poison/caffeine
-overdose/overview.html
6.http://www.erowid.org/chemicals/caffeine/caffeine_healt
h.shtml
7.http://content.nejm.org/cgi/content/abstract/327/16/110
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References Continued
8. Fredholm, B,B., Battig, Karl, Holmen, Janet., Nehlig, Astrid, and
Zvartau, E. Action of Caffeine in the Brain with Special References to
Factors That Contribute to Its Widespread Use. (1999) The American
Society for Pharmacology and Experimental Therapeutics. Vo. 51.
No. 1
9. Fisone, G., Borgkvist, A.., Usiello, A., Caffeine as a Psychomotor
Stimulant: Mechanism of Action. 2004. Cell. Mol. Life Sci. 857-872