Caffeine and anxiety

Caffeine is one of the most popular and widely consumed psychostimulant substances. The main source of caffeine is coffee, which has spread throughout the world thanks to its taste and both stimulant and antioxidant properties. However, it can also produce unwanted effects that depend on various factors such as age, sex, our state of health and genetics.

Caffeine is a substance found naturally in the leaves, seeds and fruits of more than 60 plants such as tea leaves, kola nuts, and coffee and cocoa beans. It can also be synthesised artificially and added to food products and certain medicines.

At low doses, caffeine produces mild euphoria, alertness and enhanced cognitive performance. At high doses, however, it can cause nausea, anxiety, jitteriness and nervousness.

When a person consumes caffeine on a regular basis, they are generally tolerant to the effects produced by caffeine. However, some people are more sensitive to the anxiety produced by caffeine or suffer from insomnia when caffeine is consumed, and therefore take less caffeine or avoid caffeine.

Caffeine can be used for short-term relief of fatigue or drowsiness, but not everyone responds equally, nor is everyone as tolerant of its adverse effects. The variability in caffeine consumption between individuals may be explained, in part, by genetic factors that influence caffeine metabolism or affect other physiological processes related to the effect of caffeine, such as sensitivity to anxiety.

Caffeine acts by blocking adenosine receptors, a neuromodulator of the central nervous system that slows down neuronal functions and causes sleep. This substance has a psychostimulant effect and an anxiogenic (anxiety-generating) effect.
Several studies have evaluated the variation in the regulation of anxiety when mutations occur in the genes responsible for the adenosine receptor system, specifically in the A2a or ADORA2A gene. The fact that these mutations produce changes in the ADORA2A gene may affect the functionality of the adenosine receptors and that caffeine acts on them to a greater or lesser extent by changing the degree of competition of caffeine with adenosine reception and sleep production.
In addition, the receptors are known to interact physically and the binding of adenosine to the A2a receptor reduces the affinity of the DRD2 receptor for dopamine, a stimulant neurotransmitter involved in the brain's reward system.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

1 variant


Childs E., Hohoff C., et al. Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 2008 Nov;33(12):2791-800.

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