Coffee does not affect everyone in the same way. While one person feels better focus, more energy and improved performance, another experiences a racing heart, inner restlessness, tremor, worse sleep or anxiety. This is not simply about having a “more sensitive personality.” Research shows that genetic differences play a role in the response to caffeine, especially in systems involved in caffeine metabolism and its action in the brain.
To understand coffee sensitivity, it helps to start with adenosine. Adenosine is a substance that gradually accumulates in the brain during the day and contributes to the feeling of fatigue, slowing down and the need for rest.
Caffeine works by blocking adenosine receptors, mainly A2A receptors, thereby “releasing the brakes” on the nervous system. The result is increased alertness, less sleepiness and higher activation.
In some people this effect is pleasant and useful. In others, however, it can turn into unpleasant overstimulation, inner tension or anxiety. It depends on how sensitive the given nervous system is and how quickly the body breaks down caffeine.
People’s reactions to coffee are not the same because several biological factors come into play. One part of the difference relates to how quickly the organism metabolizes caffeine. Another part relates to how sensitively the receptors in the brain, through which caffeine acts, respond.
This is precisely why the same dose of coffee can have a completely different effect in two people. One feels more alert and focused. The other feels “overstimulated,” has worse concentration, is restless or experiences anxiety.
One of the best-studied genes is CYP1A2. This gene encodes an enzyme in the liver that is involved in breaking down caffeine. In some people this system works faster, in others more slowly.
This has practical significance. If caffeine is broken down more slowly, it remains in the body longer and its stimulant effect lasts longer. This can mean a more pronounced impact on sleep, greater restlessness in the afternoon or evening, and stronger perception of side effects after the same amount of coffee.
In simple terms: two people drink the same cup, but one “burns off” the caffeine faster and the other feels it for much longer.
Another very important gene is ADORA2A, which is related to adenosine receptors in the brain. It is here that caffeine blocks the effect of adenosine, thereby influencing the regulation of alertness, sleep and tension.
Research shows that variations in this gene may be associated with higher sensitivity to the effects of caffeine on anxiety and sleep. In other words, in some people caffeine more easily triggers restlessness, a racing heart or more difficulty falling asleep. So it is not only about how much coffee you drink, but also about how sensitive your adenosine system is.
Interestingly, some studies have also shown a relationship between the ADORA2A genotype and the usual amount of coffee consumed. This suggests that sensitivity to caffeine may also influence how much coffee a person maintains as a long-term habit.
Caffeine does not only affect fatigue and alertness. The brain systems for adenosine and dopamine are interconnected. This is important because dopamine is related to motivation, reward, the feeling of “I want to continue” and partly also to why coffee is so attractive for some people.
Research also describes that dopamine genes, such as DRD2 and DAT1, may contribute to the variability in response to caffeine. In some people, caffeine may lead to a more pronounced activation of the reward and motivation system, but in more sensitive individuals this activation may manifest rather as inner tension, irritability or restlessness. This is why some people describe coffee as something that “gets them going well,” while others perceive it as unpleasantly agitating.
One classic study showed an association between variants in the ADORA2A and DRD2 genes and anxiety induced by caffeine. In people who received a moderate dose of caffeine, it turned out that genetic differences could influence how strongly they experienced anxiety.
At the same time, study reviews confirm that genetic differences in the CYP1A2 and ADORA2A genes can modify the relationship between caffeine and brain-related outcomes, such as anxiety, insomnia or cognitive performance. This means that sensitivity to coffee is a real biological phenomenon, not just a subjective impression.
Sleep is often one of the first areas where sensitivity to caffeine becomes apparent. Caffeine can prolong the time it takes to fall asleep, reduce sleep quality or worsen the feeling of being rested in the morning after waking up. In more sensitive people, these effects appear even with smaller amounts or even when drinking coffee in the afternoon.
From a clinical perspective, it is important to note that a person may not only have trouble falling asleep after coffee. Sometimes subtler symptoms appear: a restless evening, more difficulty “quieting thoughts,” higher inner activation or a feeling that the body cannot switch into a calm mode.
Sensitivity to coffee is worth attention especially if the following repeatedly occur after caffeine:
If a person observes these symptoms long term, it makes sense not only to ask “how much coffee is normal,” but to reflect on individual sensitivity, stress, sleep and overall psychological load.
In practice, it is often useful to start with simple self-observation:
For some people, reducing the dose, shifting caffeine to an earlier time of day, or completely avoiding it during periods of higher load helps. Sometimes it is not about banning coffee as such, but about the fact that the organism is simply more sensitive to caffeine in a given phase of life.
If coffee regularly leads to significant anxiety, palpitations, insomnia or worsening of psychological stability, it is appropriate to look at the situation in a comprehensive way. In some cases, caffeine may only accentuate already existing overload of the nervous system, an anxiety disorder, lack of sleep or long-term stress.
At EUNOMA Clinic, we approach such difficulties in context. Not only through caffeine itself, but also through the overall psychological state, sleep routine, lifestyle, level of load and the individual biological setup of the person.
Sensitivity to coffee is not random. From a biological perspective, it is mainly influenced by:
Therefore, coffee can be a useful tool for one person and an unnecessary stressor for another. The best recommendation is thus not “coffee yes” or “coffee no,” but to know your own reaction and adapt the dose, timing and overall daily routine accordingly.
I have been working in the field of addiction counselling for more than 10 years. I hold a bachelor’s degree in Addictology from the First Faculty of Medicine and a degree in General Medicine from the Second Faculty of Medicine, Charles University. In my research, I focus on preventive medicine and epidemiology.
In my work with clients, I combine evidence-based knowledge with a holistic approach to mental health. My medical background enables me to understand the broader clinical context and to better support each client’s individual needs.
