For more than 8000 years people all over the world have used cannabis, among other things in rituals and as a medicine. Just over a hundred years ago it was even the most prescribed medicine for complaints such as sleeplessness, pain and inflammation. 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. Much is also known by now about how cannabidiol (CBD) acts on the endocannabinoid system and the body as a whole. 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. As mentioned, it was discovered in 1990, when research was being done into how tetrahydrocannabinol (THC) works in our body. Scientists then found that our body naturally produces compounds that are virtually identical to the THC, CBD and other cannabinoids we find in the cannabis plant. 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 are structurally the same as compounds we also come across in cannabis. There are various endocannabinoids, including anandamide, 2-AG and TRPV1. 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 spring into action and ensure, for instance, that your temperature rises or that inflammation is countered, 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)
What is interesting about endocannabinoids and phytocannabinoids is that they are not exactly the same, but these molecules do have the same effect on the receptors of the ECS. In other words: the body does not respond differently to the compounds from the cannabis plant than it does to the compounds our body produces naturally. And that largely explains the ‘magic’ of cannabis too: it is a plant that seems to have been made to work with our body.
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 structurally alike, which means they both have the same effect on the CB1 receptor. As a result they have the same effect on our body too.
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.
In people whose endocannabinoid system functions well, there is always enough anandamide available to stimulate appetite, for instance. Through stress or conditions, though, it can happen that your body produces too little anandamide.
Taking THC is then a (temporary) way of topping up the body’s own supply of anandamide, as it were. The only problem is that this way you soon get too much THC/anandamide in your body, with the familiar negative 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. In that way it means THC has less effect in the brain and counters the worst (negative) side effects of THC.
Besides reducing the effects of THC, CBD also regulates the release of the enzyme FAAH, which is responsible for breaking down anandamide. In that way CBD means less anandamide is broken down and more of it remains 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 an average CBD oil contains virtually all the cannabinoids 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.
