1. A Small Dose of Caffeine – 04/22/10 An Introduction To The Health Effects of Caffeine A Small Dose of Caffeine

2. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 What Is This? N N N N CH 3 O O 1 3 7

3. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Caffeine – 1,3,7 Trimethylxanthine N N N N CH 3 O O 1 3 7

4. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 History of Coffee Date Event ~850 - Coffee beans discovered - The fable says that an Ethiopian goat or sheepherder noticed that the goats were more alter after eating the wild berries. He then sampled this new delicacy. ~1100 - First coffee trees and roasting of coffee beans. 1475 - Constantinople – the world’s first coffee house. 1600s - Coffee enters Europe and moves quickly to the Americas 1700s - Coffee house open throughout Europe. 1723 - First coffee plants are introduced into the Americas. 1822 - First espresso machine is created in France. 1938 - First instant coffee invented by the Nestlé company. 1971 - Starbucks opens its first location in Seattle, Washington's Pike Place Market.

5. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Caffeine & Money The coffee and cola industries owe their wealth to the physiological properties of the drug caffeine. S.G. Gilbert (2001)

6. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 History of Tea Date Event 3000 B.C. - Tea discovered in China or introduced form India 350 B.C. - First written description of Tea drinking in China. 450 A.D. - Turkish traders bargain for Tea and the Silk road is born. 800 - Tea introduced to Japan. 1450 - Japanese Tea ceremony created and popularized 1610 - Dutch bring Tea to Europe 1773 - Boston Tea party, rebellion against England’s tea tax 1776 - England sends first Opium to China to help pay for tea. 1835 - First experimental tea plantations in Assam, India. 1908 - Tea bags invented in New York.

7. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 History of Chocolate Date Event 400 B.C. - Olmec people of Mexico made chocolate drinks 250 A.D. - Mayans of Mexico were cultivating cocoa crops 1528 - Cocoa was brought to Spain by Hernando Cortés 1600s - Chocolate drinks introduced into Europe 1657 - First English chocolate houses open 1828 - Screw press that extracted the cocoa butter from the beans invented in Holland 1840s - Chocolate as solid developed

8. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Quote – Lovers of Coffee Coffee Black as hell, strong as death, sweet as love. Turkish proverb.

9. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Quote – Fear of Coffee "Often coffee drinkers, finding the drug to be unpleasant, turn to other narcotics, of which opium and alcohol are most common.“ Morphinism and Narcomanias from Other Drugs (1902) by T. D. Crothers, M.D.

10. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Quote – Love of Tea “Tea, though ridiculed by those who are naturally coarse in their nervous sensibilities … will always be the favorite beverage of the intellectual.” Thomas De Quincey (1785–1859), English author. Confessions of an English Opium- Eater,“The Pleasures of Opium” (1822).

11. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Quote – Religion and Drugs If Christianity is wine, and Islam coffee, Buddhism is most certainly tea. Alan Watts, The Way of Zen, 1957

12. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Tea trade and opium Opium War of 1839-42 Great Britain has a monopoly on the sale of opium which it forces on China; eventually gaining control of Hong Kong. Consider our societies ongoing “war on drugs”. Historical Events

13. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Caffeine and Society  Most widely consumed stimulant drug in the world  Many people start consuming caffeine at an early age  A great deal of money is made from caffeine – why?

14. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Exposure Most widely consumed neuroactive compound Coffee Soda Products Tea Chocolate

15. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Caffeine Content 1 Cup of coffee – 65-175 mg 1 Cup of tea – 50 mg Can of soda (12 oz) – 40-50 mg Bar of chocolate (30 g) – 1-35 mg

16. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Exposure and Effects Have you every drank too much caffeine? What are the effects?

17. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Aspects of Caffeine Desirable effects Stimulant, increased alertness, concentrate, energy, bronchial dilator Toxicity Restlessness, jitters, anxiety, insomnia, elevated or irregular heart rate No tolerance Most develop little or no tolerance to the nervous system effects Withdrawal effects Transient but persistent, headache, low energy, in ability to concentrate

18. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Rapidly absorbed following oral consumption Peak blood (plasma) levels usually with 30 minutes Absorption

19. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Distributes into all body compartments – Pass easily into brain, breast milk and crosses placenta Does not accumulate Distribution

20. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10  Metabolized in the liver  Changed to di- and mon- methylxanthines  Excreted in the urine Metabolism/Elimination

21. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 How long it takes to leave the body Average adult – 3-5 hrs Child less that 6 months – 24 hrs Pregnant – 7-8 hrs Smoker – 2-3 hrs Varies between individuals Half-life

22. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Theophylline – 1,3 Dimethylxanthine N N N N H CH 3 O O 1 3 7

23. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Blocks Adenosine receptor Adenosine is a calming neurotransmitter Mechanism Of Action

24. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Parents Of Caffeine Parent of compounds found in RNA & DNA PURINEXANTHINE Dioxypurine - Parent methylxanthines

25. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Adenosine Receptor Adenosine Cell Membrane Signal Protein Positive Response Calming effect Positive Response Calming effect Outside Cell Inside Cell Adenosine binds to receptor 11 33 22 Normal Action of Adenosine

26. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Caffeine 11 inactivates receptor Caffeine inactivates receptor No Response Resulting in Stimulation No Response Resulting in Stimulation 33 22 Action of Caffeine Adenosine Receptor Adenosine can not bind Adenosine can not bind Caffeine

27. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 1.Pleasant stimulant effects 2.Short Half-life (you need to back for more) 3.Can’t drink too much at any one time (toxicity) 4.Headache when you stop drinking it Why so many $$s from caffeine?

28. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 A Small Dose of ™ Caffeine

29. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Additional Information  Web Sites England – Department of Health – Statement on the reproductive effects of caffeine. Online. (accessed: 2 April 2003). U.S. Food and Drug Administration (FDA) - Perplexities Of Pregnancy. Online. (accessed: 9 April 2003). Caffeine – The Vaults of Erowid. Online. (accessed: 2 April 2003).

30. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”

31. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Xanthine N N N N H H H O O 1 3 7

32. A Small Dose of ToxicologyA Small Dose of Caffeine – 04/22/10 Purine N N N N H 1 3 7