Question: Many of us like to drive a cup of coffee every morning or after lunch to keep us awake. However, some say coffee makes people sleepy instantly. So I am wondering how coffee, or caffeine (the main chemical responsible for the effect of coffee), is working in our central nervous system. What does it do to our brains?

Answer: Caffeine affects our nervous system mainly in three ways, according to the review article carried by Nelig et. al (1992). Caffeine is able to alter the intracellular calcium concentration, to inhibit the activity of the phosphodiesterase, and to inactivation of the adenosine receptor. Calcium plays an major role in signal transduction, especially in chemical synapses and neuromuscular junction. The relationship between caffeine and intracellular calcium concentration comes from the researches on skeletal muscles. It hasd been shown that caffeine is able to lowers the active potential threshold of the muscle, and able to prolong the activation of the muscle. In chemical synapses, electric signal from the presynaptic neuron activates the calcium channel, allowing the calcium to flow into the cytosol, either from extracellular space or endoplasmic reticulum. This calcium influx would activate the release of neurotransmitter, allowing them to bind onto the receptor of the postsynaptic neuron, and passing on the signal. The calcium channel on endoplasmic reticulum can be bound by caffeine, thus changing the amount of calcium released into the cytosol. Phosphodiesterase is the enzyme responsible for the degradation of cyclic nucleotides, like the cyclic AMP (cAMP). Besides the effect of regulating the level of sugar and glucagon in our body through the activation of cAMP-dependent protein kinases, cAMP as a secondary messenger is also the signal for the release of norepinephrine and epinephrine. As caffeine inhibits the phosphodiesterase, the level of cAMP in cell would increases, which leads to the release of epinephrine from adrenal gland, and norepinephrine from sympathetic nerves. These chemicals act on the heart, increasing the heart rate and blood pressure, and providing more oxygen to our brain.3 In combination with the effect of the cAMP-dependent protein kinases, the metabolism in brain neurons would be increased.  Adenosine receptor is the specific receptor that adenosine, a neuromodulator molecule in central nervous system, would bind to. Adenosine is the product of ATP degradation, and it is accumulated in our brain during the wake time. Once the adenosine receptor is bounded and activated, it would slows the neural activity down, and causes sleepiness. Caffeine is the antagonist of the adenosine receptor. By competitively binding to the adenosine receptor, the neural activity would not be slow down as it should be, thus preventing the sleepiness caused by the adenosine.

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  1. Astrid Nehlig, Jean-Luc Daval, Gérard Debry, Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects, Brain Research Reviews, Volume 17, Issue 2, May–August 1992, Pages 139-170, ISSN 0165-0173,
  2. “Effects of Caffeine.” Effects of Caffeine. Accessed June 21, 2016.
  3. Smatresk, N. J. (n.d.). How does caffeine affect the body? Retrieved June 21, 2016, from
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  5. THE BRAIN FROM TOP TO BOTTOM. Retrieved June 21, 2016, from