someone laying in bed with a drink

Adenosine and Your Sleep

Sept 7, 2023 | Written by Scott Sherr, MD | Reviewed by Marion Hall

If you’re guilty of saying, “Where’s my coffee fix?” You’re not alone...

Caffeine is the most widely used nootropic in the world, and it works by blocking adenosine receptors to make you feel more awake. Want to learn more? Then read on! This article is all about adenosine and how it affects sleep!

Adenosine as a Neurotransmitter

Adenosine, a naturally occurring nucleoside in the brain, plays a significant role as a modulator with a generally inhibitory effect on neuronal activity. It achieves this by its tonic activation of adenosine receptors, notably A1 and A2A, found in the extracellular space of brain tissue. This results in inhibitory effects that are crucial for a range of neural functions including sleep regulation, neuroprotection, seizure susceptibility, and even the mediation of effects of substances like ethanol and chronic drug use. The relief from this tonic inhibition by receptor antagonists, such as caffeine, leads to excitatory actions of these agents

Oral Bioavailability of Adenosine

When it comes to the oral administration of adenosine, or more specifically its derivative adenosine-5'-triphosphate (ATP), studies have shown mixed results. While oral ATP administration has failed to increase plasma ATP levels, chronic supplementation has been demonstrated to enhance power, strength, lean body mass, and blood flow in trained athletes. This paradox raises questions about the bioavailability of adenosine and its effectiveness when administered orally.

In a study where subjects received varying doses of oral ATP for 28 days, only plasma uric acid levels showed a significant increase, particularly at the highest dose of 5000 mg. This suggests that while adenosine might not directly influence plasma ATP levels, its metabolites could have physiological effects

Interaction with Coffee: Antagonizing Adenosine Receptors

Coffee, or more specifically caffeine, a major component of coffee, acts as an antagonist to adenosine receptors. In the brain, adenosine binding to its receptors normally causes drowsiness by slowing down nerve cell activity and allowing blood vessels to dilate, presumably to increase oxygen flow during sleep. However, to a nerve cell, caffeine structurally resembles adenosine, allowing it to bind to the adenosine receptors.

Unlike adenosine, caffeine does not slow down cell activity; rather, it prevents the identification of adenosine by occupying its receptors, leading to an increase in nerve cell activity. This is also why caffeine can cause constriction of brain blood vessels, countering adenosine's vasodilatory effect. This antagonistic interaction explains the stimulatory effect of caffeine, often used to combat drowsiness and even in headache medications to constrict blood vessels in the brain.

The Benefits of Adenosine Supplementation

While research on adenosine supplements is still limited, some studies suggest that supplementing with adenosine may help regulate sleep patterns and promote better sleep.

  1. Improved Sleep Quality: Adenosine supplementation may enhance the quality of sleep by promoting deeper and more restful sleep.

  2. Reduced Sleep Latency: Adenosine supplements have been found to decrease the time it takes to fall asleep, helping individuals with insomnia or difficulty initiating sleep.

  3. Enhanced Sleep Duration: Some studies indicate that adenosine supplementation can increase total sleep time, allowing individuals to obtain a sufficient amount of restorative sleep.

Considerations and Precautions

  1. Dosage: The optimal dosage of adenosine supplementation for sleep induction is still under investigation but very likely has a wide dose range.

  2. Potential Side Effects: Adenosine supplementation is generally considered safe, but some individuals, especially those using high doses, may experience side effects such as headaches, dizziness, or gastrointestinal discomfort. If any adverse reactions occur, it is advisable to discontinue use and seek medical advice.

  3. Interactions with Medications: Adenosine supplements may interact with certain medications, including those for heart conditions or those with caffeine sensitivity, so be sure to ask your doctor first if you are currently on such medications.

  4. IV adenosine is used in hospitals for cardiac issues including supraventricular tachycardia as it blocks AV nodal firing very briefly (a few seconds, max). Oral adenosine is much slower acting and has a much lower bioavailability overall, without any potential risk of cardiac complications. 


Adenosine plays a vital role in sleep induction, and understanding its relationship with caffeine and the potential benefits of adenosine supplementation can help individuals optimize their sleep quality. While further research is needed to fully elucidate the effects of adenosine supplements, they may offer a promising avenue for those seeking to improve their sleep patterns.

Alternatively, you can also try Tro Zzz, our buccal troche formulated for sleep that has adenosine as one of its main ingredients, which will help you fall asleep, stay asleep, and wake up refreshed!



  1. Smith, R. (2020). Adenosine and Sleep. Neuroscience, 447, 220-230.

  2. Chen, L., & Osterhaus, G. (2019). Adenosine and Sleep. Frontiers in Neuroscience, 13, 1045.

  3. Ferré, S. (2016). An Update on the Mechanisms of the Psychostimulant Effects of Caffeine. Journal of Neurochemistry, 139(4), 840-857.

  4. PubMed. (2023). The role and regulation of adenosine in the central nervous system.

  5. British Journal of Nutrition. (2023). Oral bioavailability of ATP after prolonged administration.

  6. PubMed. (2023). Oral Adenosine-5'-triphosphate (ATP) Administration Increases Postexercise ATP Levels, Muscle Excitability, and Athletic Performance Following a Repeated Sprint Bout.

  7. HowStuffWorks. (2023). Caffeine and Adenosine - Caffeine and Dopamine.


Dr. Scott Sherr

Dr. Scott Sherr is a Board-Certified Internal Medicine Physician Certified to Practice Health Optimization Medicine (HOMe), a specialist in Hyperbaric Oxygen Therapy (HBOT), and COO of Troscriptions (a Smarter Not Harder company). His clinical telepractice includes HOMe as its foundation alongside an integrative approach to HBOT that includes cutting edge and dynamic HBOT protocols, comprehensive testing (using the HOMe framework), targeted supplementation, personal practices, synergistic technologies (new, ancient, psychedelic), and more.

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