CBD and Adenosine: Exploring Their Interactions and Benefits

A cup of CBD-infused coffee placed beside a flower, with text overlay reading "CBD and adenosine".

You may not have ever heard of adenosine before, but it is the reason that most coffee drinkers need their first cup in the morning. Adenosine is a neurotransmitter that can make you tired in the morning and later in the evening, but it can do so much more. It’s also at the mercy of our favorite cannabinoid. CBD and adenosine research is still lacking, but we’ll talk about why we may want to direct more attention towards their interaction.

In this post, we’re going to cover

What adenosine is
How adenosine interacts with our brains
How CBD can affect adenosine interactions
And what that means about CBD’s potential benefits

What Is CBD?

The abbreviated form of cannabidiol, CBD is one of the 100+ cannabinoids produced by flowering hemp plants. CBD is non-psychoactive, meaning that its consumption will not make you feel high or intoxicated like THC would.

While experts are still unsure about how CBD interacts with your body, we do know that it works closely with your endocannabinoid system— an intricate network of neurotransmitters, receptors, and enzymes. Your endocannabinoid system helps manage your bodily functions like,

Sleep
Mood
Appetite
Memory
Central Nervous System Development
And more…

What Is Adenosine?

Adenosine is an endogenous neurotransmitter made up of a nitrogen base (adenine) combined with a sugar molecule (ribose). Adenosine can combine with one, two, or three phosphate groups forming adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), respectively.

By itself, adenosine is a neuromodulator, meaning that it can influence the activities of the neurotransmitters around it like dopamine and glutamate. One of its primary functions is to calm the central nervous system by promoting relaxation and drowsiness. Adenosine builds up in your brain over the course of the day, making you feel more tired as the day wears on.

Note that caffeine (the psychoactive substance found in coffee) works against adenosine, blocking it from binding with the appropriate receptors resulting in feelings of alertness. Beware though that this effect will only last for so long before your brain’s neurotransmitters eventually win out.

How Does Adenosine Work?

Much like melatonin, adenosine is a chemical that works on a 24-hour schedule as part of our circadian rhythm. More and more adenosine builds up in the body as the day goes on.

Adenosine controls certain functions in your body by binding to specific receptors in your brain and central nervous system. Said receptors are important to many of our day-to-day functioning and worth a closer look.

A1 Receptors:

When activated, the A1 receptor curbs neurotransmitter release which can have a calming effect on the brain. Fewer chemicals flying through your brain means that you’re more calm. A1 receptors are involved in sleep regulation, pain management, and heart rate regulation.

A2A Receptors:

Found primarily in the part of the brain that links motivation to motor skills and decision-making, the A2A receptors can both stop or facilitate neurotransmission— the ability of neurons to share information with each other.

A2B Receptors:

Found in various tissues like blood vessels and white blood cells, A2B receptors help with immune response, inflammation, and reducing blood pressure.

A3 Receptors:

Similar to A2B receptors, A3 receptors are located throughout your body and help regulate your immune system, its response to external threats, and inflammation.

How Does CBD Affect Adenosine?

The interaction between CBD and adenosine is understudied, but there have been some cursory findings.

CBD has been found to increase adenosine signaling by inhibiting the reuptake of adenosine.¹ When CBD prevents the reuptake of adenosine, it effectively increases adenosine availability in your body. This surplus of adenosine must go somewhere, so it activates the four A receptors listed earlier, promoting a sense of calm, relaxation, and sleepiness.

It may be these adenosine interactions that give CBD its benefits.

Anti-Anxiety effects:

Adenosine and the A2A receptors may help alleviate stress and anxiety symptoms by promoting relaxation²

Anti-Inflammatory effects:

Adenosine has anti-inflammatory effects. CBD’s influence and uptake inhibition may further enhance adenosine’s anti-inflammatory potential.³

Sleep Benefits:

While not thoroughly studied, we can extrapolate and hypothesize that CBD and its interaction with adenosine may help regulate sleep. Adenosine increases an individual’s sleep pressure, and when inhibited from reentering your brain, excess adenosine is likely to make you more tired.

Further Study Is Needed

Research into CBD and adenosine interactions is still new, but the emerging findings are promising. As more rodent studies show promise for CBD therapeutic uses, we may even start to see human trials. For now, most findings into adenosine and its interactions with cannabidiol and cannabinoids at large are one-off and should be taken with a grain of salt.

Sources:

Carrier, Erica J et al. “Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression.” Proceedings of the National Academy of Sciences of the United States of America vol. 103,20 (2006): 7895-900. doi:10.1073/pnas.0511232103
Stollenwerk, Todd M et al. “Contribution of the Adenosine 2A Receptor to Behavioral Effects of Tetrahydrocannabinol, Cannabidiol and PECS-101.” Molecules (Basel, Switzerland) vol. 26,17 5354. 2 Sep. 2021, doi:10.3390/molecules26175354
Mecha, M et al. “Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors.” Neurobiology of disease vol. 59 (2013): 141-50. doi:10.1016/j.nbd.2013.06.016