Question: As a student, I have had many experiences with caffeine. Caffeine can be a godsend. I always have a cup of coffee during the day and during the afternoon slump. I’ve noticed that when I don’t have my morning or afternoon coffee, I get irritable. It is hard for me to focus, and I use all of my energy trying to keep alert. Needless to say, these negative side effects are due to my body withdrawing from caffeine. My questions are what is caffeine’s mechanism of action and what happens to your body during withdrawals.

Answer:  Caffeine, or 1,3,7-trimethyxanthine, is one of the most widely abused substances in the world. According to the FDA, the average person in the United States consumes up to 300 milligrams of caffeine per day (Somogyi). Methylxanthines are structurally related to uric acid and act as competitive antagonists at adenosine receptors (Chawla et al.). The blockage of adenosine receptors is caffeine’s predominant mechanism of action. In the brain, adenosine reduces the amount of neuronal firing and inhibits synaptic transmission and neurotransmitter release; this makes you feel “tired” (Chawla et al.). Caffeine inhibits the effects of adenosine and helps increase the neurotransmitter turnover of molecules like monoamines and acetylcholine. These neurotransmitters help you feel awake and activate other secondary messengers, which help regulate other pathways like glycolysis and lipid metabolism.

A double blind study conducted by Dr. Suzette Evans found that when regular coffee drinking subjects were restricted of caffeine, they were more tired, their mood decreased, they were less alert and they had a headache (Evans & Griffiths). These results suggest that caffeine withdrawal is a real thing. Dr. Evans noted once-a-day dosing with 100 mg of caffeine or more is enough to produce physical dependence in some subject. Caffeine dependence is correlated with how fast your body can metabolize caffeine. In subjects where caffeine has a short half-life, they may never form a physical dependence if they consume caffeine at low amounts (Evans & Griffiths). Caffeine is a useful drug used by millions a day. However, it can lead to addiction and physical dependency. As with any substance, it is best to use caffeine in moderation. After writing this, I think decaf coffee will now be my morning drink of choice.


Figure 1: Effects of substituting placebo for different maintenance doses of caffeine on selected measures. Bars show mean peak ratings or scores for the last 2 caffeine days at each caffeine maintenance dose and the corresponding 2-day placebo substitutions; brackets show +1 S.E.M. (n = 17). *, significant difference between caffeine and placebo for a given maintenance dose.†, placebo substitution at the 600-mg caffeine dose was significantly different from placebo substitution at the 100-mg caffeine dose (p < .05). Range of possible ratings or scores for all measures is 0 to 4 (Evans & Griffiths).

  • Scott I.

Works Cited

  • Chawla, J., Suleman, A., & Lorenzo, N. “Neurologic Effects of Caffeine”. Medscape,
  • Web. (2015).
  • Evans, S. & Griffiths, R. “Caffeine Withdrawal: A Parametric Analysis of Caffeine
  • Dosing Conditions”. The Journal of Pharmacology and Experimental
  • Therapeutics, Vol. 289: 285-94. (1999).
  • Somogyi, Laszlo. “Caffeine Intake by the U.S. Population”. Food and Drug
  • Administration, Web. (2010).