Many studies have found that caffeine has anti-depressant like effects and that consuming caffeine regularly is inversely related with depression.

Caffeine: A miracle drug?

Posted Ramona Richard, MS, NC Blog

Millions of people around the world consume caffeine in various forms. Caffeine is in tea, coffee, chocolate, and sodas. It is the most widely used psychoactive drug in the world.[1] Upon ingestion of one of the aforementioned beverages or foods, caffeine is rapidly absorbed by the digestive tract and distributed to the brain and various organs.[2] Caffeine metabolism varies from person to person, but typically has a half-life of 3 to 7 hours.[3] While it is nearly impossible to overdose on caffeine, overconsumption can have some negative consequences. Caffeine intake in children has increased by 70% in the past 30 years.[4] Consumption of caffeine by children and overconsumption by adults can induce anxiety, cause panic attacks, and increase stress hormone levels.[5] Drinking moderate amounts of coffee or caffeinated tea regularly as an adult has very few negative side effects, however. In fact, many studies have found that caffeine has anti-depressant like effects and that consuming caffeine regularly is inversely related with depression.[6][7] It also appears that individuals who consume caffeine throughout adulthood are less likely to develop dementia and Alzheimer’s.[8] One study found that elderly women who had consumed coffee throughout their lives had enhanced memory and performed better on cognition tests.[9] While caffeine can cause some mental and physiological dysregulation, it is so popular for good reason.


Adenosine is a lesser-known neuroactive molecule responsible for inhibiting excitatory signals in the brain and promoting sleep. An understanding of adenosine function is necessary to further explain the mechanism of action and effects of caffeine. Caffeine is a competitive antagonist of adenosine receptors (ARs), meaning it binds to ARs and prevents adenosine from doing its job.[10] Many people may remember adenosine from a biology class, as it is a component of ATP (adenosine triphosphate), the main form of cellular energy.[11] Adenosine on its own, though, is actually a neuromodulator. Unlike other neurotransmitters, adenosine is not released in response to an action potential, it does not act at the synapse, and it is not stored in vesicles.[12] Adenosine is ubiquitous in the body and present in nearly all cell types.[13] Its function is primarily inhibitory, as it decreases neuron firing and inhibits neurotransmitter release.[14] Dopamine, GABA, glutamate, and acetylcholine are all modulated by adenosine.[15] Levels of adenosine rise throughout the day, which helps the body suppress arousal closer to bedtime and thus promote sleep.[16] This gradual rise in adenosine prevents sleep deprivation and energy depletion.[17] Caffeine, as a competitive antagonist of ARs, prevents these inhibitory functions of adenosine.

How does caffeine work?

Caffeine, like all drugs, ultimately gets metabolized by the liver. Cytochrome p450 in liver cells breaks caffeine down into three components: paraxanthine, theobromine, and theophylline.[18] Theophylline is a type of molecule called a methylxanthine. Methylxanthines reduce the uptake and metabolism of catecholamines, which are responsible for excitation in the body, leaving more of these excitatory neurotransmitters available.[19] Theophylline also relaxes the muscles of the lungs and digestive tract.[20] Theobromine dilates blood vessels, which is one reason that caffeine consumption can help relieve headaches and migraines.[21] The hypothalamus is the brain’s control center, where neuroendocrine signals are sent and retrieved. Adenosine receptors on the hypothalamus are antagonized by caffeine. This antagonism results in signals from the hypothalamus to tell the pituitary to stimulate stress hormone release from the adrenal glands.[22] Therefore it is common to see cortisol surges in patients who drink coffee throughout the day. ARs are also located on the hippocampus, which regulates cognition and memory. Caffeine prevents adenosine’s inhibition of hippocampal ARs, which is why coffee can promote enhanced cognition.[23] The orbitofrontal cortex and temporal lobe are densely packed with ARs, and these areas of the brain continue developing into young adulthood.[24] This is one of the reasons caffeine consumption (and subsequent AR alteration) can be contraindicated for children.

Caffeine, adenosine, and dopamine

Drugs of abuse nearly always alter dopamine level or function in some way. Dopamine promotes salience, or positive reinforcement and reward-seeking behavior. Drugs of abuse can induce dopamine’s positive effects and create a “high” feeling, but long-term drug use often depletes dopamine or desensitizes dopamine receptors. AR activation by adenosine typically inhibits dopamine transmission, so, as caffeine prevents this inhibition, dopamine levels go up.[25] While caffeine acts on the dopaminergic system, it does not act on dopaminergic structures related to reward, motivation, and addiction like many drugs do.[26] However, long-term use of caffeine can alter the ratio of ARs in the brain and cause a tolerance to caffeine’s effects, but withdrawal from caffeine use typically only lasts a few weeks, while ARs return to normal.[27]

While caffeine use is typically safe, it does have serious negative implications when mixed with alcohol. Alcohol blocks adenosine reuptake, which elevates the activity of adenosine.[28] This elevation is part of the reason alcohol makes you sleepy. Caffeine has the opposite effect on adenosine activity. The addictive properties of alcohol are somewhat stifled by this feedback. Alcohol increases adenosine, which then decreases dopamine, reducing the chance of alcohol abuse and dependence.[29] Caffeine, by blocking adenosine function, allows dopamine to elevate with alcohol intake. This lack of negative feedback on alcohol consumption makes alcohol far more likely to cause addiction and deplete dopamine. Indeed, beverages containing a combination of alcohol and caffeine are now illegal (such as the popular drink FourLoko, which is now sold without added caffeine). Caffeine is relatively safe and potentially even beneficial in the aging process as long as it is consumed after the brain has completed its development— and not in combination with other drugs. The L-theanine in Lentra™ may mitigate some of the effects of caffeine.

Enjoy drinking coffee or tea to start your day and thank adenosine for getting you to sleep at night!

[1]Kaster, M. P., Machado, N. J., Silva, H. B., Nunes, A., Ardais, A. P., Santana, M., . . . Cunha, R. A. (2015). Caffeine acts through neuronal adenosine A2Areceptors to prevent mood and memory dysfunction triggered by chronic stress. Proceedings of the National Academy of Sciences, 112(25), 7833-7838. doi:10.1073/pnas.1423088112

[2] Fisone, G., Borgkvist, A., & Usiello, A. (2004). Caffeine as a psychomotor stimulant: mechanism of action. Cellular and Molecular Life Sciences (CMLS), 61(7-8), 857-872. doi:10.1007/s00018-003-3269-3

[3] Chawla, J., & Suleman, A. (2011). Neurologic effects of caffeine.

[4] Temple, J. L. (2009). Caffeine Use in Children: What we know, what we have left to learn, and why we should worry. Neuroscience and Biobehavioral Reviews, 33(6), 793–806.

[5] Patz, M. D., Day, H. E. W., Burow, A., & Campeau, S. (2006). Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine. Psychoneuroendocrinology, 31(4), 493–500.

[6] Ribeiro, J. A., & Sebastião, A. M. (2010). Caffeine and Adenosine. Journal of Alzheimer’s Disease, 20(S1). doi:10.3233/jad-2010-1379

[7] Kaster, M. P., Machado, N. J., Silva, H. B., Nunes, A., Ardais, A. P., Santana, M., . . . Cunha, R. A. (2015). Caffeine acts through neuronal adenosine A2Areceptors to prevent mood and memory dysfunction triggered by chronic stress. Proceedings of the National Academy of Sciences, 112(25), 7833-7838. doi:10.1073/pnas.1423088112

[8] Ribeiro, op. cit.

[9] Ribeiro, Ibid.

[10] Chawla, op. cit.

[11] Mori, A. (2014). Adenosine receptors in neurology and psychiatry. Amsterdam: Academic Press.

[12] Mori, Ibid.

[13] Ribeiro, op. cit.

[14] Chawla, op. cit.

[15] Mori, op. cit.

[16] Marczinski, C. A., & Fillmore, M. T. (2014). Energy drinks mixed with alcohol: what are the risks? Nutrition Reviews, 72, 98-107. doi:10.1111/nure.12127

[17] Ribeiro, op. cit.

[18] Ribeiro, Ibid.

[19] Chawla, op. cit.

[20] Ribeiro, op. cit.

[21] Ribeiro, op. cit.

[22] Patz, op cit.

[23] Riberio, op. cit.

[24] Temple, op. cit.

[25] Fisone, op. cit.

[26] Chawla, op. cit.

[27] Riberio, op. cit.

[28] Marczinski, op. cit.

[29] Marczinski, op. cit.


Clinical Contributor

Sophie Thompson

Sophie Thompson

Clinical Support Specialist at Sanesco Health
Sophie recently obtained her degree in Biology from UNCA in Asheville. Born and raised in Asheville, her hobbies include painting, writing and spending quality time with her dog and her family.
Sophie Thompson

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    Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.