Caffeine: The Motivation Molecule

1,3,7-trimethylxanthine (C₈H₁₀N₄O₂), also known as caffeine, is the most commonly used psychoactive drug in the world. Potentially, you’ve consumed more than 100 mg by the time you’re reading this post. While the average is about 135 mg per day according to Harvard University T.H. Chan School of Public Health, that amount varies depending on the vehicle.

Caffeine is most associated with coffee and was first isolated from the coffee bean by Ferdinand Runge in 1819. The Library of Congress recently acquired Neueste Phytochemische Entdeckungen (Latest Phytochemical Discoveries), the 1820 publication that contains his experimental results, which is currently in process with a catalog record forthcoming. In these experiments (pgs. 144-159), Runge applied a variety of reagents to both raw and roasted beans in order to determine what chemical compounds were present.

Tables showing Runge’s experimental results from coffee beans, both raw (left) and roasted (right). Runge, Ferdinand. Neueste Phytochemische Entdeckungen, pp. 154-55.

The table above, printed in a font that is (or very closely resembles) fraktur, lists the reagents in the left-most column and the substances tested at the top of the remaining three columns. These substances are listed as Coffee Base, Caffeic Acid No. 1, and Caffeic Acid No. 2 and the reagents used included hydrochloric acid, metal oxides, egg white, and gallic acid to name a few. Results of the tests led Runge to believe that his coffee-experimenting predecessors incorrectly lumped two or all three of these substances into one during their experiments (e.g. coffee base + caffeic acid no. 2). In a parting shot, Runge shaded French chemist Armand Seguin by refuting the latter’s assertion that a bitter substance was present in the bean:

Such a substance is not found in unbrewed coffee, you only have to put a bean in your mouth to be sufficiently convinced of it.

While Runge’s experiments isolated caffeine, the first known use of the word was in 1821 by Pierre Joseph Pelletier in his “cafeine” entry that appeared in Dictionnaire de Médecine: 35-6. Pelletier performed further analysis on the makeup of caffeine and published those findings in Annales de Chimie et de Physique in 1823. He found caffeine to be composed of carbon, nitrogen, hydrogen, and oxygen, stating that the nitrogen content was not only greater than in any known vegetable alkalis, but also that of animal matter. Pelletier also noted in this entry that some doctors believed coffee to be a febrifuge (fever reducer) and that further experiments were needed on this front.

Coffee Arabica; leaves, flowers and fruit. Painted from nature by M.E. Eaton – Detail sketches show anther, pistil, and section of corolla. Ukers, William H. All About Coffee, p. 1.

Black coffee is concentrated sunshine. This sentiment is often credited to Alexander von Humboldt. However, in an 1836 letter to Heinrich Christian Schumacher (Bruhn, 1872), von Humboldt credited old Delisle as saying a half cup of black coffee is  “concentrirte Sonnenstrahlen” or concentrated sunbeam.  The observed physiological effects of caffeine feels more of a wake-up than the sunrise itself and can include enhanced problem solving, improved logical reasoning, rapid information processing, and improved cognitive function.

Caffeine is, relative to loads of other molecules, quickly absorbed into the bloodstream. This quick uptake is due to its ability to easily pass through cell membranes; it can even make its way through the blood-brain barrier! This ability to pass through tissue also keeps it from accumulating in your organs. And because caffeine isn’t fat soluble, it doesn’t accumulate in body fat either. The half-life of caffeine is 2-4 hours so by the time you’re winding down for bed, nearly all of it from that morning cup of coffee is out of your system.

No matter how you consume it, caffeine is an ever-present molecule that gives us seemingly endless energy. You can use some of that energy to drink up the following resources for more information:

• Bruhns, Carl. Eine Wissenschaftliche Biographie, im Verein mit R. Ave-Lallemant, J.V. Caru, [u.a.]. v. 2. 1872: 62.
• Bruhns, Carl. Life of Alexander von Humboldt. v. 2. 1873:56.
• Dumas and Pelletier. Recherches sur la composition élémentaire et sur quelques propriétés caractéristiques des bases salisiables organiques. Annales de Chimie et de Physique, series 2, v. 24. 1823: 163-190. [cafeine pages 181-2].
• Harvard University T.H. Chan School of Public Health: Caffeine
• NIH MedlinePlus: Caffeine
• Pollan, Michael. This is Your Mind on Plants. 2021.
• Spiller, Gene. Caffeine. 1998.
• Ukers, William. All About Coffee. 1922.
• Weinberg, Bennett and Bonnie Bealer. The World of Caffeine: The Science and Culture of the World’s Most Popular Drug. 2001.