How Does Caffeine Work?

Have you ever wondered how that cup of coffee can reliably wake you up every morning? Let's discuss exactly what caffeine is doing in your brain.

How Does Caffeine Work?
Photo by Mark Daynes / Unsplash

Author: Jarret Morgan, PharmD Candidate
Editor: Brentsen Wolf, PharmD

Caffeine is cool, but how does it work? For some background, feel free to read our previous article on the potential benefits of coffee and the recommended daily amount of caffeine for adults.

As a current first-year pharmacy student and frequent gym goer, I’m no stranger to caffeine. From early morning cups o’ joe to pre-workout energy concoctions, I seem to love it in any form. But how does it work, and why am I so tired if I miss my morning dose? After addressing these questions, we will discuss caffeine cycling to maximize its benefits.

Caffeine is well known as a central nervous system stimulant. In order to wake you up in the morning, the individual molecules of caffeine must breach the blood-brain barrier, which is an exceptionally cool name for the semipermeable membrane protecting your brain. Lucky for caffeine, it can readily dissolve in both water and fat. In other words, caffeine is on the VIP list to make its way into your brain, but what exactly does it do there?

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Once caffeine enters your brain party, it can start to fulfill its purpose of inducing the alertness and wakefulness that we all crave. It specifically does this by blocking adenosine receptors in your brain. For those who speak pharmacology, caffeine antagonizes adenosine receptors through competitive inhibition. This means that caffeine isn’t causing any effect, but preventing one. See, adenosine is essentially a co-captain to melatonin when it comes to sleep. At the end of the day, adenosine receptors begin to fill up with adenosine molecules to help communicate to your brain that you are exhausted and tired. If you block this receptor, you won't feel the adenosine-induced tiredness. Unfortunately for us, there is a caveat.

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Let's say you drink 1 cup of coffee every single morning for 6 weeks. Your brain cells will start to notice the inhibition of adenosine receptors and it will counteract caffeine by upregulating the receptor itself. This is how you build up a tolerance. If you want the same effect, you now must block more adenosine receptors than before, requiring another cup of coffee to feel the same alertness. There is a direct relationship between caffeine intake and adenosine receptor concentrations. This means if you drink less caffeine, the adenosine receptor concentration will decrease. I should emphasize that process is neither proportional nor immediate. Cutting your caffeine intake in half today would not cut your adenosine receptor concentration in half tomorrow. However, a gradual approach to decreasing your caffeine intake would decrease your adenosine receptor concentration over time.

Now, say you decide to take a break from caffeine after a prolonged and consistent relationship has been developed. You now have a lot more adenosine receptors than before, so when adenosine comes flooding back, you will feel exceptionally more tired than if you had never ingested any caffeine in the first place. Basically, if you miss your morning dose, you have a mob of adenosine molecules coming after you. You can expect to suffer from one or more of the common caffeine withdrawal symptoms like a pounding headache, among others. You might think, why would I want to take a break if it causes me pain and symptoms?

If you cycle your caffeine usage, you can potentially maximize its benefits (increased focus, energy, mood, and appetite suppression). Taking a break can help reduce your tolerance. The same can be done with alcohol. You can take full days off or just decrease your intake on certain days of the week. Perhaps you consume your standard 3 cups of coffee throughout the week, but you cut back on the weekends when you can afford to wake up slowly. Whatever works best for you.

Just remember, sometimes, you really can have too much of a good thing.