CBD and the endocannabinoid system

For more than 8000 years people all over the world have used cannabis, among other things in rituals and as a medicine. In the nineteenth century cannabis was also used in Western medicine. At that time, though, people did not yet know how cannabis works and why it has the effects it has.

Fortunately that has since changed. In 1990 the endocannabinoid system (ECS) was discovered and a great deal of research has been done into it ever since. A lot of research is also being done into CBD and the endocannabinoid system, although much is still unclear. What exactly is the ECS, what role does the ECS play in our body and what does CBD do to the ECS?

What exactly is the endocannabinoid system?

The endocannabinoid system is a kind of communication system that is present throughout our body, particularly in the brain and other organs. It was discovered through research into how tetrahydrocannabinol (THC) works: around 1990 researchers found the receptor THC acts on, and in 1992 the first compound the body makes itself that fits that same receptor. Cannabinoids of the body’s own, then, or endocannabinoids. And as with everything in the body, those endocannabinoids are not there for nothing but are part of a system, as the scientists soon discovered: the endocannabinoid system (ECS).

With the discovery of the ECS it first became clear how THC in particular makes people feel ‘high’ after smoking cannabis. But over the past decades research has shown that the ECS plays an important role in regulating and controlling a large number of bodily functions:

• Memory and learning
• Processing emotions
• Sleeping and waking
• The internal thermostat, so regulating body temperature
• Pain and the experience of pain
• Motor skills and coordination
• Inflammatory responses
• Immune response
• Digestion (particularly appetite)

What does the ECS consist of?

The ECS consists of a network that is especially common in the brain, but is also woven into other organs and body tissue. The ECS consists of three elements:

Endocannabinoids

These are molecules our body produces naturally and that fit the same receptors as compounds from cannabis, even though they are built differently. The two best-known endocannabinoids are anandamide and 2-AG. In the ECS, endocannabinoids fulfil the function of keys, which fit the locks we call receptors.

Receptors

Receptors are not only locks that the keys called endocannabinoids fit, but also fulfil important regulating functions. The two best-known cannabinoid receptors are CB1 and CB2.

Enzymes

Enzymes are responsible for producing and breaking down cannabinoids and so ensure, for instance, that anandamide is broken down or produced.

Cannabinoid receptors: CB1 and CB2

So the two most important receptors of the ECS are CB1 and CB2 receptors. These are, incidentally, not the only receptors of the system, because it was recently discovered that a receptor called GPR55 plays a role too. But we will leave that aside for now.

CB1 receptors are among the most common receptors in the brain and in the spinal cord. They occur mainly in the hippocampus, the basal ganglia, the frontal cortex and the cerebellum, but are also found in the liver, the lungs and the reproductive organs, among others. Their main function is regulating the level of neurotransmitters in the nervous system. In that way they ensure, for instance, that you get hungry or that your body temperature rises.

CB2 receptors are less common in the brain, but are found mainly in parts of the immune system. The skin, bones, liver and pancreas contain CB2 receptors as well. The function of CB2 receptors is different from that of CB1 receptors, because CB2 mainly ensures that inflammatory responses are regulated.

Endocannabinoids and phytocannabinoids

Before receptors can carry out their regulating function, they first have to be activated. And that is where the cannabinoids come in, because these are, as mentioned, the keys that fit the lock of the receptors. Cannabinoids come in two forms:

• Cannabinoids of the body’s own (endocannabinoids)
• Cannabinoids from cannabis plants (phytocannabinoids)

Endocannabinoids and phytocannabinoids are different molecules, but some of them fit the same receptors of the ECS. That explains why compounds from the cannabis plant can act on this system. How strongly and in what way differs per compound: THC activates the CB1 receptor, CBD does not.

THC, anandamide and the ECS

Particularly when we look at THC from cannabis and the body’s own anandamide (named after the word ‘Ananda’ from Sanskrit, which means something like bliss), it becomes clear how cannabis can have the effects it has. THC and anandamide are built differently, but both activate the CB1 receptor.

And that effect is considerable. Because when anandamide or THC binds with all the CB1 receptors located throughout the brain, all those functions that those parts of the brain regulate are activated too. And this is what the compound anandamide owes its name to and THC its psychoactive action, because it makes you feel euphoric, makes your short-term memory less active, raises your temperature, makes you sleepy and stimulates your appetite.

THC mimics anandamide, but the body breaks THC down much more slowly than anandamide. That makes the effect stronger and longer-lasting, with the familiar side effects as a result.

CBD and the endocannabinoid system

Unlike THC, CBD acts on the ECS in a different way and is not psychoactive. That is part of why CBD is getting so much attention at the moment, why CBD is legal and why CBD oil and other CBD products are so much in the spotlight. There is still quite some uncertainty in science about exactly how CBD works, but we do know a fair amount about it by now.

What we know, among other things, is that CBD does not bind to the CB1 and CB2 receptors in the same way as THC and CBG, for instance. What CBD does do is change the shape of the CB1 receptor, with the result that THC (and anandamide) can bind to it less well. Research suggests that CBD may temper the psychoactive effect of THC in this way.

In addition, CBD may inhibit the enzyme FAAH, which is responsible for breaking down anandamide. That way more anandamide may remain in the body. What that means in practice is still the subject of research.

CBD is a food supplement and not a medicine. There are currently no EU-approved health claims for CBD, so we make no promises about what it does. Do you have persistent complaints? Then discuss them with your GP.

Other cannabinoids and the ECS

Besides THC and CBD, more than 100 cannabinoids are known. And of those, CBG, CBN and CBC are currently getting the most attention. Here too research is still in full swing, but we do know the following about how these cannabinoids act on the ECS:

• CBN binds mainly to CB1 receptors, but less than THC. It also has some affinity for CB2 receptors. What that binding means is still the subject of research.
• CBC does not bind strongly to CB1 or CB2 receptors, but does act on the so-called TRPA1 and TRPV1 receptors. It influences the reuptake of the body’s own endocannabinoids. What that means is still being researched.
• CBG, known as the ‘mother’ of all cannabinoids, binds to both CB1 and CB2 receptors (and to serotonin and adrenergic receptors as well). Here too, what that means is still being researched.

So it is not only how CBD acts on the endocannabinoid system that is interesting, that of all the other cannabinoids is fascinating too. But when you consider that a full spectrum oil contains other cannabinoids alongside CBD and that these therefore all act on the ECS together at the same time, you understand that we are only at the beginning of a long and complex search for the mechanism behind it.

Frequently asked questions about the endocannabinoid system