From the French Emperor, Napoleon Bonaparte, who declared “I would rather suffer with coffee than be senseless”; To the American- British poet, T.S. Eliot, who said “I have measured out my life with coffee spoons”; To the American TV host, David Letterman, who proclaimed “if it wasn’t for coffee, I’d have no identifiable personality whatsoever”: It is evident that humanity’s indulgence and perhaps reliance on caffeine stretches back across the ages.

It’s no surprise that on university campuses, caffeine is a major part of students’ lives. Market research by the Beverage Marketing Corporation has shown that coffee is the most popular late-night study aid and an early morning eye opener on campus. However, whether it’s tea, energy drinks or coffee; students inevitably consume caffeinated drinks frequently. In an anonymous survey given to US college students from five geographically dispersed US universities, 92% of the students claimed to consume caffeine and 79% said ‘to feel awake’ as their justification for consuming caffeinated drinks. In another survey administered to 300 freshmen at a south eastern US university, 83% reported having at least one sign/symptom of caffeine intoxication [1]. So, before indulging in a fifth cup of our favourite caffeinated beverage of the day, let us delve into the neuropharmacology behind caffeine, and whether it can cause more harm than good.

Caffeine (1,3,7-trimethylxanthine) is a plant alkaloid with a chemical structure of C8H10N4O2 and is the most widely used CNS stimulant in the world. Caffeine’s elimination half-life ranges from 1.5 – 9.5 hours; this wide range is due to innate individual variation and environmental characteristics that influence caffeine metabolism e.g. obesity, smoking, pregnancy.

The main mechanism of action of caffeine is its ability to inhibit adenosine receptors. These receptors have an important effect on cognitive function and behaviour. Neurons break down adenosine triphosphate for energy. One of the resulting breakdown products is adenosine. Hence, as the brain uses up more energy, the concentration of adenosine increases inside the neurons. These adenosine molecules leave the neurons and bind to adenosine receptors leading to drowsiness. This mechanism is important as high adenosine levels indicate prolonged high levels of activity, and therefore, the need to rest. If adenosine activates A1 receptors present on wake stimulating neurons, those neurons, in turn, become less active, however, if adenosine activates A2A receptors present on sleep promoting neurons, those become more active. The effects of adenosine binding to both these receptors together promotes sleepiness. During sleep, the brain replenishes its energy reserves and adenosine levels drop. Eventually there’s insufficient adenosine levels to activate the adenosine receptors so you wake up feeling refreshed.

The similar structure of caffeine to adenosine allows caffeine to act as a competitive antagonist. Since adenosine and caffeine aren’t exactly identical, caffeine cannot activate adenosine receptors. Instead it acts to block and prevent binding of adenosine to its respective receptors. Therefore, if adenosine is unable to bind to adenosine receptors, the brain will remain active and a person will feel more awake.

Another possible mechanism of action of caffeine is its ability to inhibit phosphodiesterase enzymes in skeletal muscle and adipose tissue. This would explain for caffeine’s cardio stimulatory and anti- asthmatic actions. Inhibition of phosphodiesterase increases intracellular concentration of cyclic adenosine monophosphate (cAMP). These actions promote lipolysis via activation of hormone sensitive lipases and lead to an increase in blood catecholamines. Some catecholamines induce physiological changes: increasing heart rate, blood pressure and blood glucose.

Numerous medical studies have been carried out to determine the benefits and drawbacks of coffee. A 2011 paper by the European Food Safety Authority claims that coffee improves cognitive function ny increasing alertness. This study reviewed 22 randomised double- blind placebo-controlled trials of the effects of caffeine on attention. Overall, there was a cause and effect relationship between a 75mg caffeine (1 regular cup) and increased selective attention, sustained attention and alertness [3].

A study done by John Hopkins University in 2014 concluded that coffee enhanced consolidation of long- term memory in humans. A double-blind placebo controlled randomised trial was carried out. 160 students were given caffeine or placebo after learning a list of words and were tested 24 hours later. They found that at least 200mg of coffee is needed to observe the enhancing effect on consolidation of memory.

Coffee consumption is also negatively correlated with some long-term health problems such as Alzheimer’s, Parkinson’s, type 2 diabetes and cancer. A 2018 study showed a statistically significant inverse correlation between coffee consumption and development of type 2 diabetes. A meta-analysis was carried out that analysed 1 million people. They concluded that the risk of type 2 diabetes decreased by 6% for each cup per day in coffee consumption.

Furthermore, a 2010 study of 1409 individuals aged between 65-79 examined them over a 21-year period. It showed coffee consumption in midlife reduced the risk of developing Alzheimer’s disease and dementia in the elderly with a 65% reduced risk in groups that had between 3-5 cups of coffee per day.

Conversely, too much coffee can cause anxiety, restlessness and agitation. There is also evidence that consuming a lot of caffeine late in the day can negatively impact quality of sleep. A 2013 study explored the effects of caffeine if consumed 0, 3 or 6 hours before going to bed. Researchers gave a 400mg dose of caffeine or a placebo to volunteers at varying times before bed. Consuming caffeine 6 hours, 3 hours or even just before going to sleep was found to have had a detrimental impact on quality of sleep. Based on the results of these studies, one should avoid consuming caffeine at least 7 hours before bedtime.

It is apparent that caffeine, and in turn coffee, possesses numerous benefits. However consuming caffeine excessively can lead to health issues. Current NHS guidelines recommend drinking no more than around 4 cups of coffee per day for a healthy adult; equivalent to 400mg of caffeine [8]. It is necessary to strike a balance to ensure you are reaping the benefits of coffee but not suffering from its consequences. As 19th century British Prime Minister Benjamin Disraeli said, “The choicest pleasures in life lie within the ring of moderation.”