CB1 & CB2 Receptors

Written by OLIG CBD

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CB receptors: understanding how CBD works in your body

The endocannabinoid system

In the early nineties, Israeli Professor Raphael Mechoulam and his team disclosed their scientific findings about the endocannabinoid system. A decade of mounting evidence and scientific research led to the identification of two major receptors involved in CBD processing: CB1 and CB2.

It was the beginning of a great adventure. Even though CBD products have gained a lot of press since, it is still unclear to many people how CBD actually works in the body. It is generally understood that the endocannabinoid system plays a key role in brain functions, immunity, hormonal regulation as well as stress management. However, the exact process by which CBD works on those areas of human health is less known.

 The endocannabinoid system relies on a series of receptors in the body. It is postulated by current research that there are many of these endocannabinoid receptors, however, as of today, only CB1 and 2 receptors are well understood. To some extent, both are found in the whole body, though the receptors are more densely located in differing areas and organs.

How does it work?

 

Three types of cannabinoids

There are three types of cannabinoids to which these receptors respond:

endocannabinoids, which are cannabinoids naturally occurring in the body,

phytocannabinoids, which are cannabinoids contained in plants, and

synthetic cannabinoids.

Scientific research established that phytocannabinoids and synthetic cannabinoids can bind with endocannabinoid receptors, therefore allowing cannabinoids from an outside source to engage with the body’s natural system. In fact, CBD does not directly activate the receptors. Instead, it signals our own endocannabinoids to activate them. This means CBD tells our body how to balance itself, which makes it an extremely well tolerated medicine. CBD is non-competitive, which is to say it does not take the place of our natural endocannabinoids. It rather communicates with them, helping the body to deal with any imbalance using its own tools.

When in good health, the endocannabinoid system regulates itself by producing endocannabinoids. However, if there is an imbalance, resulting from health issues or stress for instance, this system might become cannabinoid deficient. In this scenario, taking cannabinoids derived from a plant source can help restore balance. CBD manages this by telling our endocannabinoid system it needs to produce more endocannabinoids.

Anandamide

To understand how this works we can turn to Mechoulam’s findings, which shed light on the function of anandamide. This neurotransmitter was found to be involved in the regulation of appetite, sleep, mood and the immune system. The word ‘anandamide’ is derived from the Sanskrit ananda, literally meaning “bliss.” This name underlines the capacity for that neurotransmitter to bring back balance in our mood and well-being. Anandamide is also involved in the THC high, as well as in the euphoric state generated by a good work-out session.  

Our bodies generate anandamide to maintain equilibrium, also known as homeostasis. A high level of anandamide reduces the sensation of pain. Anandamide binds to the CB1 and CB2 receptors.

2AG

Another endocannabinoid triggered by CBD is 2-AG, short for 2-Arachidonoylglycerol. The latter is an agonist to both CB1 and CB2. It is the primary binder for the CB2 receptors. 

This endocannabinoid plays a role in the regulation of immune and reproductive functions, in bone health, sleep and mood regulation, as well as in pain management. It was the second endocannabinoid to be discovered, in 1995. With this, came the discovery of a cannabinoid network in the nervous system.

Retrograde signalling

One of the most notable characteristic of endocannabinoids is that they work contrary to other neurotransmitters. Most neurotransmitters go from the presynaptic cell to the postsynaptic cell while endocannabinoids follow the reverse path. In this sense, endocannabinoids interact with what is received, and act as a form of shield to undesirable stimuli such as pain. In short, cannabinoid receptors can signal to cells on the presynaptic end, providing a feedback loop to regulate neurotransmitter and hormone release.

CB1 receptors

CB1 receptors are mostly located in the brain, spine and central nervous system. They are also to be found in the lungs, kidneys, reproductive organs, the liver, gastro-intestinal tract, pancreas, muscles and immune system. They are associated with pain relief and anxiety regulation. These receptors also interact with THC.

Endocannabinoids released by depolarized neurons bind to the CB1 receptors of specific presynaptic neurons, connected with glutamate and GABA handling. This results in a decrease in the glutamate and GABA release. GABA, or gammaAminobutyric acid, is an inhibitory neurotransmitter, responsible for muscle tone and the reduction of neuronal excitability. Glutamate is involved in the biosynthesis of proteins and is a precursor for the synthesis of GABA. The effect of the decrease in glutamate release is relaxation, which partly explains how the CB1 receptor is involved in pain relief. Meanwhile, the effect of the decrease in GABA release is to activate cells on the other end of the synapse.

CB2 receptors

CB2 receptors are mostly located in several organs, such as the spleen, liver and pancreas. They are present in the blood, skin and bones and are associated with the immune system.

The endocannabinoid activity on the CB2 receptors impacts the levels of cyclic adenosine monophosphate (cAMP). The latter is involved in intracellular signal transduction, and plays a role in transferring hormones to the cells, including adrenaline.

The effects of this activity include a facilitation of cell migration. It also supports the natural death of cells at the end of their life cycle, and regulates immune suppression. Research is currently looking at the connection between cAMP and cancer, with a huge potential for CBD based cancer cures. 

Through the inhibition of immune cell migration, endocannabinoids that bind to the CB2 receptor have the potential to relieve inflammation, which is a form of immune response.

CB2 receptors are therefore involved in immune regulation, inflammation reduction and pain relief. They are also at the forefront of research to treat serious conditions such as AIDS and cancer. 

A large spectrum of therapeutic properties

The effect of CBD on endocannabinoid receptors CB1 and CB2 therefore has a very large spectrum of effects. We might discover more of them in the coming years, hence the excitement of the scientific community around CBD research.

As if this was not enough, CBD also effects a series of other important receptors which are not part of the endocannabinoid system. This includes serotonin, vanilloid and adenosine receptors. Serotonin is involved in mood regulation and is famous as the well-being neurotransmitter. It has a large spectrum of effects on appetite, cognition, mood, sleep, temperature regulation and more. The vanilloid receptors are involved in the regulation of inflammation, pain and body temperature. Lastly, the adenosine receptors are involved in reducing inflammation, maintaining cardio-vascular health and supporting brain function.

There is therefore a vast amount of research yet to be done to better understand endocannabinoid receptors and the effects of CBD on other types of receptors. It is possible that future findings will be important keys to treat cancer, depression and a whole host of other conditions plaguing our modern-day societies.