1. Don’t Forget-What Information Will be Covered for EVERY Drug:
What is drug?
Why is it used?
How is it administered?
How much is used?
Metabolism?
Affects on the cell?
Addiction?
Benefits?
Harms?
Individual experience may vary

2. Caffeine Nicotine Caffeine (it IS a drug!) Lesson 16 Cocaine
Amphetamines
Ecstasy
Anti depressants

3. What is caffeine? Why is it used?Activity2
Keeping us alert!!
Coffee 150
Tea 75
Mountain Dew 55
Chocolate 15
Redbull 115
Monster 190
Sobe – guarana 75 mg
Excedrin – 65 mg per tablet
NoDoz – 100 mg per tablet
Alkaloid found in many plants, including coffee beans, cacao pods, kola nuts and tea leaves

4. What are some caffeine forms?
WHY?
Plentiful in ground water!
Coffee 150
Tea 75
Mountain Dew 55
Chocolate 15
Redbull 115
Monster 190
Sobe – guarana 75 mg
Excedrin – 65 mg per tablet
NoDoz – 100 mg per tablet
Justin from Lincoln Park, NJ

5. How is caffeine administered? Activity 3
Parenteral or not?

6. Which has the highest caffeine dosage?
What about?
Coffee 150
Tea 75
Mountain Dew 55
Chocolate 15
Redbull 115
Monster 190
Sobe – guarana 75 mg
Excedrin – 65 mg per tablet
NoDoz – 100 mg per tablet 2 4 5 6 3 1

7. Why so little caffeine in chocolate!?
Theobromine
Theophylline
All are Xanthines
CH3 = methyl group
For instance, arsenic is 25+ times more toxic if methylated!
Mg per 12 oz drink
About chocolate – while it has some caffeine, most of the stimluant contained in chocolate is a different member of the xanthine family – theobromine and tea has more theophylline (xanthine stimulant too).
Energy drinks can also contain non-stimulant ingredients such as L-carnitine which is an amino acid involved in lipid metabolism (and therefore useful for weight loss AND energy production – mitochondria stimulated) and Taurine (taurus – originally found in high concentrations in ox bile) is useful as anti-oxidant, renal promoter, cofactor in visual system…
SOME of the drug response differences between individuals is related to the ability to deal with these methyls!

8. Is there a lethal dosage of caffeine?
One caffeine death – 90 No-Doz pills (100mg each) approx = 250 cups coffee
No hard data on lethal dose, but seems to be about 10 g

9. How is Caffeine metabolized? Activity 4
CYP1A2 H
84% is paraxanthine
- rest is theobromine and theophylline
Insomnia – not adenosine receptor (though agonists treat it and give LOTS of side effects). Two main causes are mania – sympathetic over action and a prion disease that is like CJD !(?)
Half life 3-7 hours

10. What happens to CYP1A2 as you continue to use caffeine day after day?
Your CYP2A1 gets used up
Your CYP2A1 is produced in an anticipatory way
Your CYP2A1 works more and more poorly
You stop making CYP2A1 because your thrifty body realizes you’re drinking it instead

11. How does caffeine effect a cell? Activity 5
adenosine
Insomnia – not adenosine receptor (though agonists treat it and give LOTS of side effects). Two main causes are mania – sympathetic over action and a prion disease that is like CJD !(?)

12. Adenosine receptors and alertness1 2 3
Without adenosine on it’s receptors, a neuron fires.
Neurons signal to the hypothalamus to activate RAS. Hypothalamus, using reticular activating system, signals for alertness.

13. Adenosine and alertness1 2 3 x
Adenosine has an inhibitory effect. When bound, it causes the neuron to slow down or stop firing. This signals hypothalamus to stop preparing for alertness, and RAS allows person to calm down, become relaxed. Adenosine gets produced over the course of a day, filling up the receptors as it goes.

14. Caffeine and alertness
adenosine
Caffeine and alertness
caffeine 1 2 3
Caffeine fills up the space normally occupied by adenosine, adenosine cannot bind, neurons with adenosine receptors stay active, RAS stays active, person stays alert
Excess RAS activity is interpreted as stress

15. Stretch/power yoga!!!

16. How does adenosine tell you when you’re sleepy?
Noon
Adenosine receptors mostly unoccupied
8 pm
Adenosine receptors 60% full
Midnight
Adenosine receptors 90% full
Midnight (with caffeine)
Adenosine receptors filled with caffeine, not adenosine
Four receptors for adenosine – A1, A2a, A2b, A3.

17. Caffeine works as a(n):
Receptor antagonist
Receptor agonist
Adenosine catalyst
Xanthine catalyst
Reticular transporter

18. Is caffeine addictive? Activity 6
This excerpt is from DSM-IV, retrieved from
Criteria for Substance Dependence A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
(1) tolerance, as defined by either of the following:
(a) a need for markedly increased amounts of the substance to achieve Intoxication or desired effect
(b) markedly diminished effect with continued use of the same amount of the substance
(2) Withdrawal, as manifested by either of the following:
(a) the characteristic withdrawal syndrome for the substance (refer to Criteria A and B of the criteria sets for Withdrawal from the specific substances)
(b) the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
(3) the substance is often taken in larger amounts or over a longer period than was intended
(4) there is a persistent desire or unsuccessful efforts to cut down or control substance use
(5) a great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), use the substance (e.g., chain-smoking), or recover from its effects
(6) important social, occupational, or recreational activities are given up or reduced because of substance use
(7) the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).

19. Is caffeine addictive?
Adenosine is a dopamine receptor antagonist. Caffeine (double negative)…antagonist to the antagonist, therefore…
reward
tolerance
dependence

20. What genes influence caffeine habits?? Activity 9
Binds caffeine as if it was adenosine – get the same response
Adenosine receptor
PMID:
If a person’s adenosine receptors cannot recognize the difference between adenosine and caffeine, then caffeine will “appear” and function like adenosine – making that person groggy, not awake.
Adenosine receptor 2A – two polymorphisms linked to response to caffeine – those with variation are much more likely to become anxious when drinking caffeine. PMID:

21. What genes influence caffeine side effects?
CYP1A2
CYP1A2 metabolizes caffeine
CYP1A2*1A = fast metabolizer allele
CYP1A2*1F = slow metabolizer allele
7X difference
If a person’s adenosine receptors cannot recognize the difference between adenosine and caffeine, then caffeine will “appear” and function like adenosine – making that person groggy, not awake.
CYP1A1-1A = rapid metabolizers, CYP1A1-1F are slow. Slow metabolizers are more likely to have elevated risk of heart attack
*1A/*1F (“carrier”) heterozygote mixed with *1F/*1F homozygotes – 36% increase risk of heart attack with caffeine consumption (2-3 cups a day)
*1A/*1A homozygote – 22% reduced risk (2-3 cups) and 1% reduced risk (4 cups)
PMID:
*1F allele (hetero or homozygous), who also consumes caffeine, has 36% increased risk of heart attack (2-3 cups a day)
PMID:

22. The latest in benefits (and harms):
On electronic device/computer, go to the following website:
2. Enter the following (case sensitive):
Username: STADIUM-WA
Password: 7jv35ZFc33
Tracking Code: STADIUM-243
Keep this information somewhere accessible for future projects.
3. Search for the following article: The Beneficial Bean (10/3/15) Read and take notes. Question on Final.

23. Which of these groups SHOULD use caffeine regularly?
Families prone to strokes.
Families with Alzheimer’s.
People prone to addiction.
Families who also use nicotine.
Women who are pregnant.

24. Caffeine benefits (besides alertness)? Activity 7
PMID:
PMID:
PMID:
PMID: Caffeine reduces Parkinson’s risk
PMID: Caffeine may reduce risk of Alzheimer’s
PMID: Caffeine may reduce liver damage among heavy drinkers

25. What are caffeine Risks? Activity 8
PMID:
~75% as addictive as nicotine
Michael Malta
Wired!
Improved concentration ? – adenosine receptors in hippocampus
Reduces headaches (vasoconstriction) – (reduced blood flow to brain, less headache and less able to sleep) frequently found in pain-relieving meds.
Increase heart rate (and bp like all other stimulants)
Bronchodilation (asthma relief)
diuretic
Restlessness (different adenosine receptor)
Intoxication – high doses – restless, nervous, twitching, rambling
Dosage considerations
One caffeine death – 90 pills approx = 250 cups coffee
Addiction –stimulates dopamine release and adenosine antagonizes dopamine recptors – so caffeine is a double negative???

26. Interesting contradictions about caffeine and cardiovascular health
PMID:
PMID: 14
Caffeine ~3.5 8 oz cups – 43% more likely than ~1.5 8 oz cups
J nutrition – September Happonen – 2000 people studied, year old men followed for 14 years!
PMID:
PMID: (304 cups a day = 43%more cardiovascular events
PMID: (caffeine implicated in 14% of heart attacks, 20% stroke deaths)
Jane’s photo – 2-3 cups a day – drops death rate for women – Jun 17 Annals of Internal Medicine 2008 – nurses health study, 86K women, for 24 years (also 42K males for 18 y ears) – 25% lower death rate from cardiovascular disease illness, 18% lower for all combined life threatening illnesses. Not true for men in study. DECAF drops equally well!!! Jacobs Had to account for unhealthy lifestyles of coffee drinkers (such as smoking). 20
43% increased risk (men)
25% reduced risk (women)