Every day we use things without fully grasping how they work. I get it, we are often too busy to worry about learning things that would just satisfy our curiosity without really giving us tangible advantage. That’s why people drive to work without knowing how an engine works, they use bitcoins and even invest their savings in them without knowing how they work, we use computers and software without knowing how to code and most importantly we all abuse the most widely used psychoactive drug, coffee, without knowing what it does to our brain.
Certainly, you don’t need to know this to continue having a good life, but if you are at least a little curious about how coffee works, continue reading.
Especially in the western society we grew up surrounded by myths. Why do we believe myths? Because they make a good story and sometimes we’d rather believe a good story instead of a messier truth. Generally speaking, we were primed to think that if something is giving us pleasure it must be bad for us. Coffee is obviously one of the most targeted substances, despite the fact that it contains high concentrations of Flavonoids. These are potent anti-oxidant and inti-inflammatory molecules (Ref Book 1). But let’s delve into the biology.
Let’s start by having a nice cup of coffee. Each cup of coffee contains about 100 mg of caffeine (or 1, 3, 7-trimethylxanthine) (Fredholm 1995). The caffeine is absorbed in the gastrointestinal tract, at the peak levels, the amount of caffeine that can be found in our body fluids after a cup of coffee range from 0.5 to 3 mg/L. However, its half-life varies from 2 and half to 4 and half hours, this means that after few hours caffeine lose half of its biological activity (Fredholm 1995). A study found that on average in North Europe we assume a total of 300 mg per day of caffeine per person (Fredholm 1995). We drink so much coffee because often we have a very intense work life and caffeine increases our alertness and cognitive performance, plus as we will see later, it also causes the release of dopamine thus giving us a boost and a sensation of pleasure (Panza et al. 2015).
Probably the key to the biological activity of caffeine is its ability to inhibit the adenosine receptors. Oh, now that’s clear right?
Probably not, let’s see what these adenosine receptors are.
As you know ATP (Adenosine triphosphate) is the fuel of our cells. ATP is then continuously broken down and re-synthesized. Adenosine is released when ATP is broken down, this means that when a cell had high intensity of metabolic activity it will also contain plenty of adenosine. This molecule can also be released in the extracellular environment. Our brain cells can sense the presence of adenosine because they have adenosine receptors, when they bind to adenosine they signal to the cells that probably it’s time to take a break. In other words, adenosine also acts as a homeostatic regulatory factor, that orchestrates the rate of energy consumption and the supply rate of metabolites (Fredholm 1995). So when there is too much adenosine the neural cells become more lethargic. There are several different receptors for adenosine but it was found that coffee can inhibit the receptor A1 and the receptor A2.
Receptor A1: it decreases the rate of neural firing and also causes a decrease in the release of neurotransmitters. By inhibiting this receptor, caffeine increases neural firing.
Receptor A2: it’s involved in the dopaminergic transmission. By inhibiting this receptor, caffeine has an excitatory effect, causing the release of dopamine and glutamate.
So, I guess by now we are all aware of the short term effects of caffeine but there are also long-term effects. In fact, it was found that animals that were received caffeine for long periods of time developed tolerance since their brain cells started expressing more receptors A1 (Fredholm 1982). However, to determine the long term effects is not straight forward as for example caffeine was found to exacerbate the symptoms of ischemic brain damage in the short term (Dux et al. 1990) but have the opposite effect when assumed for prolonged period of time and even prevent ischemic brain damage (Rudolphi et al. 1989). Long term treatment with caffeine could decrease locomotive activity (Nikodijević, Jacobson, and Daly 1993) but increase the capacity for spatial learning (Von Lubitz, Paul, Bartus, et al. 1993).
One of the most notable and puzzling effects of caffeine is on seizures. It is known in fact that high doses of caffeine taken in short periods of time could exacerbate seizures but if caffeine is taken for prolonged periods of time it can actually have the opposite effect and have a protective effect anti-seizures (Von Lubitz, Paul, Carter, et al. 1993).
A more recent study also found that prolonged intake of caffeine and tea, prevents the insurgence of cognitive impairment/decline and dementia in elderly people. However, the authors of the research did not find a direct correlation between dose and protective effect, but they found the women benefit more than men from assumption of caffeine (Panza et al. 2015).
Overall, the balance is net positive for the assumption of caffeine, there are downsides (as anything if you take too much of it). But coffee is not as bad as we first thought. Drinking a couple of cups of coffee can enhance your productivity as long as you don’t drink it in the evening, in that case it will affect your sleep and make you tired and unproductive the day after. About the addiction to coffee it could probably be associated with his inhibitory effects on the receptors A2. As a result, more dopamine and glutamate will be released in your brain, giving you euphoric addictive feelings (Huang et al. 2005).
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