You had me at… Caffeine

You had me at… Caffeine

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By: Meital Yerushalmi and Jonathon Chio

Methyltheobromine, otherwise known as caffeine,1 is a central nervous system stimulant and the world’s most popular drug. In its pure form, caffeine is a white, bitter-tasting powder,2 which lends its psychoactive properties to many popular foods and beverages. Naturally found in the leaves and seeds of various plants, caffeine sources include coffee beans, cocoa beans, kola nuts, tea leaves, yerba mate, and guarana.3 Caffeine is also added to some prescription and over-the-counter medications, including cough, cold and pain remedies.2

While caffeine is a popular drug engrained in our culture, its use as a stimulant and a social drink is not unique to modern times and dates centuries back. Yet, the abundancy of caffeine-containing plants around the world makes it challenging to pinpoint its origins.4 In Arabia, caffeine was discovered in the coffee bean (Coffea arabica), while in China, it was found in the tea leaf (Thea sinensis). In West Africa, caffeine was discovered in the kola nut (Cola nitida), and in Mexico, it was found in the cocoa bean (Theobroma cacao). Interestingly, the etymology of the word coffee originates from Arabia, where “qahwah” (coffee) translates to “a drink made from plants”.5, 6 A famous tale recounts the discovery of the stimulant properties of caffeine, dating back to 850 AD Egypt, where an Arabic goat herder named Khaldi shepherd his flock. One night, Khaldi’s goats didn’t return home and he found them dancing around a shrub of red berries, which were actually coffee beans. When he consumed the beans himself, Khaldi also began to dance.6

The first cultivation of coffee beans and subsequent production of coffee are likely traced to 15th century Ethiopia.6, 7 Popularized for its stimulatory effects, coffee quickly spread to Yemen, Turkey, and Europe. By the 17th century, coffee was introduced to the Western world. In Yemen, coffee was used to facilitate all-nighters centuries ago, as its wake-promoting qualities were cleverly exploited for religious purposes. According to a local legend, the abbot of a Yemenite monastery prescribed coffee to facilitate his monks’ nighttime prayers.8

Remarkably, since coffee and caffeine have been introduced to the Western world, they have become an integral component of everyday culture and one of the most important commercial commodities.

In fact, coffee is the world’s second most valuable traded commodity following petroleum,9 with an annual consumption of 120,000 tons of coffee worldwide.10 Americans consume 146 billion cups of coffee per year, making the United States the leading consumer of coffee worldwide,11 while Canadians follow with an annual consumption of 2.1 billion servings.12 Coffee represents 75% of all the caffeine consumed in the United States,11 and it is estimated that 85% of Americans consumes at least 1 caffeinated beverage per day13. Surely, America Runs on Dunkin.

How much caffeine is in your favorite drink?

  • Starbucks: venti, mocha-flavoured frappuccino–140 mg14
  • Tim Hortons: large ice cappuccino–150 mg15
  • Tim Hortons: medium coffee–200 mg15
  • McDonald’s: large brewed coffee–180 mg16
  • Tim Horton’s: medium Earl Grey tea–70 mg15
  • Red Bull: can–70 mg17

The caffeine content of coffee depends on its method of preparation. Yet, regardless of technique, caffeine is broken down into more than 25 metabolites in humans.18 The metabolizing efficiency of caffeine is dependent on multiple individual factors, including genetic polymorphisms, weight, sex and presence of hepatic diseases, as these factors affect the availability of caffeine-metabolizing enzymes and the concentration of caffeine receptors.13

But how does caffeine exert its effects? Three main theories have been proposed to explain the mechanism underlying the physiological effects of caffeine. First, the calcium mobility theory proposes that caffeine, an inotropic agent (compound capable of altering force and nature of muscle contractions), indirectly increases the influx of calcium into the cells. This causes an increase in the force of cardiac muscle contraction and cardiac output.10 Second, the phosphodiesterase inhibition theory proposes that caffeine inhibits phosphodiesterase, the enzyme that degrades cyclic AMP (cAMP).19 Additionally, consumption of caffeine has been shown to raise plasma levels of catecolamines, which increase cAMP by activating adenylate cyclase.19 Subsequently, there is an increase in cAMP and cAMP-dependent protein kinases, which promote glycogenolysis and lipolysis.19, 20 However, it is now recognized that the concentrations of caffeine required for both these proposed mechanisms are very high and not likely not reached in clinical or social doses. Subsequently, a third mechanism has been proposed whereby caffeine antagonizes adenosine receptors. Adenosine is an endogenous nucleoside and a neuromodulator derived from the breakdown of adenosine triphosphate (ATP), which mediates CNS depression and produces sedation.21 Caffeine is structurally similar to adenosine and competitively inhibits its binding to receptors, thereby blocking its effects.10 By this action, caffeine opposes the sleep-promoting effects of adenosine.22

In low to moderate doses (20-200 mg), caffeine produces subjective effects of increased sense of well-being, alertness, energy, concentration, self-confidence, motivation for work, and desire to talk to people.23 Peripherally, caffeine stimulates cardiac muscle, relaxes smooth muscle, and increases gastric secretions and diuresis.24 Yet, high doses of caffeine (800-1500 mg) may cause restlessness and nervousness, diuresis, gastrointestinal disturbance, hypertension, insomnia, cardiac arrhythmias, delusions, and psychosis.24, 25

In addition to its physiological properties, a discussion about caffeine is not complete without a consideration of its profound social and cultural roles. Social gatherings often involve coffee, giving rise to the many chains of coffee shops we are all familiar with. The combination of their pleasant background music, dim lighting, smell of freshly-ground coffee,26 and of course, the caffeinated beverage (and free Wi-Fi) make coffee shops the location of choice for many business meetings, study sessions and even dates. Underlying its role as a social lubricant27 is caffeine’s aforementioned effect of increasing one’s desire to talk to people, an interesting tidbit you may recall when you next reconnect with a childhood friend over a cup of coffee.


  1. Compound Summary for CID 2519: Caffeine. [Internet]. National Center for Biotechnology Information, U.S. National Library of Medicine. Available from:
  2. Caffeine. Toronto, ON: CAMH – Centre for Addiction and Mental Health; 2011 [2016]. Available from:
  3. Food Sources of Caffeine. Toronto, ON: Dietitians of Canada 2014 [cited 2016]. Available from:
  4. Persad LA. Energy drinks and the neurophysiological impact of caffeine. Front Neurosci. 2011;5:116.
  5. Cappelletti S, Piacentino D, Sani G, et al. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71-88.
  6. Fredholm BB. Notes on the history of caffeine use. Handb Exp Pharmacol. 2011(200):1-9.
  7. Carman AJ, Dacks PA, Lane RF, et al. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer’s disease. J Nutr Health Aging. 2014;18(4):383-92.
  8. Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992;17(2):139-70.
  9. Coffee in the Global Economy. San Francisco, CA: Global Exchange; 2011 [cited 2016]. Available from:
  10. Weinberg BA, Bealer BK. The world of caffeine : the science and culture of the world’s most popular drug. New York: Routledge; 2001. xxi, 394 p. p.
  11. Coffee Statistics Report 2014 Edition. Vancouver, WA: Coffee Statistics 2014. Available from:
  12. Decline in Java Consumption Speaks to Shifting Habits of Canadians. Toronto, ON: The NPD Group, Inc.; 2015 [cited 2016]. Available from:
  13. Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2016.
  14. Nutrition by the Cup: Starbucks Coffee Company; 2011. Available from:
  15. Tim Hortons – Caffeine Content. Oakville, ON: Tim Hortons Research and Development; 2015. Available from:
  16. McCafe Coffee Caffeine Content: Exis; 2015. Available from:
  17. Caffeine Content of Food & Drugs Centre for Science in the Public Interest 2014. Available from:
  18. Echeverri D, Montes FR, Cabrera M, et al. Caffeine’s Vascular Mechanisms of Action. Int J Vasc Med. 2010;2010:834060.
  19. The effect of caffeine ingestion on exercise performance. Department of Kinesiology and Health Education. Austin, TX: The University of Texas at Austin.
  20. Metabolism of Caffeine. Newark, DE: University of Delaware 2011 [cited 2016]. Available from:
  21. Bryant B, Knights K. Pharmacology for Health Professionals, 3rd ed. . Chatswood, NSW: Elsevier; 2011.
  22. Morin CM, Espie CA. The Oxford handbook of sleep and sleep disorders. Oxford: Oxford University Press; 2011.
  23. Griffiths R, Juliano L, Chausmer A. Caffeine pharmacology and clinical effects. In: Graham AW, Schultz TK, Mayo-Smith M, editors. Principles of addiction medicine. 3rd ed. Chevy Chase, MD.: American Society of Addiction Medicine; 2003. p. 193–224.
  24. Abou-Donia MB. Mammalian toxicology. Chichester, West Sussex: John Wiley & Sons; 2015.
  25. Diagnostic and statistical manual of mental disorders DSM-5. Washington, D.C.: American Psychiatric Association; 2013. Available from:
  26. Stewart L. Ask In Your Face. 2011 [cited 2016]. Available from:
  27. Rashid S. Ezine Articles. 2008. Available from: