How Caffeine Affects Your Brain Chemistry

By Jenny Lam

Image Credit: Flickr @ Paul Scott

When needing to pull that all-nighter for tomorrow’s test or to get an extra boost of energy to survive the day without falling asleep, caffeine remains a popular option for many. It’s readily available in numerous drinks, such as coffee, tea, energy drinks, and more. For some, just one coffee isn't enough; they find that they require increasing amounts of coffee to retain the same levels of alertness and attention over time. Many might wonder if caffeine addiction is actually harmful, but can a caffeine “addiction” even be considered an actual addiction? How do people develop a tolerance to caffeine in the first place?

Image Credit: Flickr @ Allen Gathman

To answer these questions, one must investigate the relationship between caffeine and adenosine, as well as how caffeine alters brain chemistry to keep people awake. Adenosine consists of an adenine (minus a hydrogen atom) attached to a ribose sugar (minus an OH group) and is naturally created in the body during digestion. Food molecules, such as glucose, are broken down by cellular respiration to generate adenosine triphosphate (ATP) to fuel vital cellular processes in our body. Most of the ATP is hydrolyzed, or broken down, into adenosine diphosphate (ADP), which can then be dephosphorylated (have a phosphate group removed) into adenosine monophosphate (AMP). AMP can be further dephosphorylated into adenosine, which can interact with certain receptors to cause various physiological effects. In the brain, adenosine acts as a central nervous system depressant, binding to receptors to promote drowsiness. Adenosine levels rise during waking hours and can be linked to why people feel more sleepy the longer they stay awake. Essentially, adenosine causes us to feel drowsy and sleepy.

On the other hand, caffeine is an adenosine-receptor antagonist. To reach the brain, caffeine gets absorbed into the bloodstream, then passes through the blood-brain barrier by passive diffusion, as it is both fat and water-soluble. Because caffeine is structurally similar to adenosine, caffeine can attach to the same receptors in the brain as adenosine without producing that same feeling of drowsiness, causing the person to feel awake and alert. Additionally, some of the brain’s natural stimulants, such as dopamine and adrenaline, work more effectively when these adenosine receptors are blocked by caffeine. However, repeated consumption of caffeine comes at the cost of changing one’s brain chemistry over time. Because caffeine occupies receptors that were originally meant for adenosine, the brain compensates by making more adenosine receptors, meaning that more caffeine is needed to fill in the empty spots and create the same feelings of alertness. This is how people develop caffeine dependence; they need to consume increasing amounts of caffeine to achieve the same effect as the initial dose. If these same people immediately cut off their caffeine consumption, the brain works to adjust to the artificially inflated number of adenosine receptors, causing withdrawal symptoms, such as headaches, fatigue, mood changes, and tiredness.

Image Credit: Flickr @ Maria Keays

Although people can build a tolerance to caffeine over time and can experience withdrawal symptoms if they suddenly quit caffeine, whether a dependence on caffeine can qualify as an actual addiction is debatable. A 2010 paper in the Journal for Nurse Practitioners states that “caffeine meets all the requirements for being an addictive substance, including dependence, tolerance, and withdrawal,” and the World Health Organization (WHO) recognized caffeine as an addictive substance in 2012. However, the National Institute on Drug Abuse for Teens (NIDA) defines addiction as “the uncontrolled (or ‘compulsive’) use of a substance even when it causes negative consequences for the person using it.” Caffeine’s withdrawal effects are generally much milder than the effects of drugs such as meth and cocaine, and a caffeine dependence does not produce the same severe and destructive behavior associated with other drug addictions. Caffeine does not cause a significant enough surge of dopamine to unbalance the brain’s reward system, and people who experience withdrawal symptoms can typically recover after 7-12 days, so the American Psychiatric Association (APA) does not currently classify caffeine dependence as a substance use disorder.

Despite this, too much of any substance, including caffeine, can be harmful, so it is important to consume caffeine in moderation. People under 18 have the recommended daily limit of 100 milligrams of caffeine, which is about one cup of coffee, and for adults, 300-400 milligrams of caffeine a day is generally regarded as a safe limit (about 3-4 cups of coffee). Caffeine has its fair share of benefits, such as reducing the risk of multiple cancers and Parkinson’s disease, as well as improving memory and reaction times, but it can also increase blood pressure, cause sleep disturbances, and heighten symptoms of anxiety and depression in the long run. In the end, it is up to you to consider the effects of caffeine and decide whether it should be a part of your life!

What did you learn?


1. Adenosine is considered a central nervous system depressant, which is a drug that slows brain activity. Does caffeine also fall into this category? Why or why not?

Caffeine is not a central nervous system (CNS) depressant; rather, it is a central nervous system stimulant, a drug that stimulates the brain to increase alertness, attention, and energy. It is also the most widely taken CNS stimulant in the world. Generally, CNS stimulants stimulate the central nervous system to speed up bodily functions (as the name states), leading to an increased heart rate, blood pressure, and sleeplessness, while CNS depressants inhibit the function of the central nervous system, resulting in lowered blood pressure, drowsiness, and lower levels of awareness.

2. Caffeine is an adenosine-receptor antagonist. What is the role of a receptor antagonist?

A receptor antagonist, also called a blocker, is a ligand (ion or molecule that binds to another molecule) that blocks or decreases a receptor’s biological response by binding to it. They inhibit the function of agonists, chemicals that bind to receptors to activate a biological response. There are several types of receptor antagonists: competitive, non-competitive, and uncompetitive antagonists. Competitive antagonists bind to the receptor’s active site, while non-competitive antagonists bind to an allosteric site. Competitive antagonists “compete” for the active site with the agonist, so increasing the concentration of the antagonist or agonist can allow it to out-compete the other one. Although non-competitive and uncompetitive antagonists sound similar, uncompetitive antagonists require activation by an agonist before binding to the allosteric site.


Image Credit:


Affiliated with:


© 2020 by The Helyx Initiative