Caffeine – the most widely consumed psychoactive drug – University of Copenhagen

NaToxAq > Toxin of the week > Caffeine

01 April 2019

Caffeine – the most widely consumed psychoactive drug

Natural toxin

A deadline is approaching. We need to stay awake late at night, working, driving cars and skippng healthy sleeping. Then, getting up early in the morning and beware approaching a busy person before their first coffee. Here is a closer look at the active ingredient’s chemistry and toxicology.

1,3,7-Trimethylxanthine, commonly known as caffeine, is one of the most widely consumed foods and supplements in the word. In Europe, the annual average consumption of coffee is around 5 kg per capita – the highest in the world1,2. Unlike other psychoactive drugs, consumption of caffeine is legal and not regulated in most parts of the world.

Naturally caffeine occurs in plant leaves, fruits and blossoms, where it most likely serves as a, insecticide and to attract pollinators3–5. The alkaloid is synthetized in plants by three methyl substitutions on a xanthine ring6.

Structures of caffeine and adenine. Click for interactive 3D image of caffeine

The structural similarity of caffeine to very basic bio-macromolecule (RNA and DNA) building blocks, the purine base adenine, which is also a modulator of nervous signal transmission it acts on the nervous system. It competes with adenosine for receptor binding and, by preventing adenosine binding, delays the sleepiness linked to adenosine receptor activation6–8. Consumed at moderate levels between 32 and 300 mg (approx. 0.5–4 mg/kg bodyweight), it improves reaction time, attention and problem solving with a peak at 30-60 min after consumption6. Additionally, it also improves physical performance of athletes during both, aerobic and anaerobic conditions, including running performance and endurance – probably due to delayed muscle and central fatigue9–11.

Reported adverse effects of caffeine include anxiety, sleeplessness, headache, nausea and elevated blood pressure, however these symptoms are transient in nature and mostly occur after exposure to high doses (≥400 mg) of caffeine5. Severe cases of caffeine intoxication are reported as well, however these occurred upon consumption of very high amounts (10 g) – often in suicide attempts5.

Caffeine is still discussed for causing adverse effects during pregnancy and development, however a cross-generational study with healthy people concluded, that the current thresholds of Intakes of ≤300 mg/day in pregnant women and ≤2.5 mg/kg-day in children and adolescents remain acceptable and do not pose a health risk5,12.

SMILES: CN1C=NC2=C1C(=O)N(C(=O)N2C)C

References:

  1. Ferro, G. & Pierrot, J. What is the demand for coffee in Europe? (2018). Available at: https://www.cbi.eu/market-information/coffee/trade-statistics.
  2. Smith, O. Mapped: The countries that drink the most coffee. (2017). Available at: https://www.telegraph.co.uk/travel/maps-and-graphics/countries-that-drink-the-most-coffee/. (Accessed: 29th March 2019)
  3. Lee, Y., Moon, S. J. & Montell, C. Multiple gustatory receptors required for the caffeine response in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 106, 4495–500 (2009).
  4. Wright, G. A. et al. Caffeine in floral nectar enhances a pollinator’s memory of reward. Science 339, 1202–4 (2013).
  5. Wikoff, D. et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem. Toxicol. 109, 585–648 (2017).
  6. McLellan, T. M., Caldwell, J. A. & Lieberman, H. R. A review of caffeine’s effects on cognitive, physical and occupational performance. Neurosci. Biobehav. Rev. 71, 294–312 (2016).
  7. Bolton, S. & Null, G. Caffeine Psychological Effects, Use and Abuse.
  8. Nehlig, A., Daval, J.-L. & Debry, G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res. Rev. 17, 139–170 (1992).
  9. Southward, K., Rutherfurd-Markwick, K. J. & Ali, A. The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta–Analysis. Sport. Med. 48, 1913–1928 (2018).
  10. Pesta, D. H., Angadi, S. S., Burtscher, M. & Roberts, C. K. The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance. Nutr. Metab. (Lond). 10, 71 (2013).
  11. Camfield, D. A., Stough, C., Farrimond, J. & Scholey, A. B. Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis. Nutr. Rev. 72, 507–522 (2014).
  12. Caffeine in Food - Canada.ca. Available at: https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives/caffeine-foods/foods.html. (Accessed: 29th March 2019)

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