Never heard of the endocannabinoid system before? You’re not alone. The relatively unknown nature of the endocannabinoid system may be due to the fact that this system was actually only discovered very recently, with the cannabinoid receptor (eventually being called the CB1 receptor) only being discovered in 1990. A few years after this, another receptor, the CB2 receptor, was discovered. Although the endocannabinoid system was only discovered very recently, and research is ongoing into its operation and effects, a lot has been discovered about the system which has proved very interesting.
We now know that that the endocannabinoid system likely has multiple different receptors mainly on the pre-synaptic neurone. The current strongest candidate for the CB3 receptor is known as the GPR55, although there are other possible candidates.
But what are CB Receptors? CB receptors are G protein coupled bio-receptors that are found throughout the central and peripheral nervous system and the rest of the body, particularly the immune system. This may partly explain why any phytocannabinoids we take which interact with our own endocannabinoid system have multiple and far-reaching medical benefits.
After the receptors were discovered, the next discovery was of the ligands. The main ligands of the endocannabinoid system are 2-arachidonoylglycerol or 2AG and anandamide.
It has been known now for a number of years that during neurotransmission, the pre-synaptic neurone releases neurotransmitters into the synaptic cleft. These neurotransmitters then bind with neuroreceptors on the post-synaptic neurone.
Overall, it appears that the endocannabinoid system acts as a modulator or controller of this basic system.
Then, once the post-synaptic neurone has been activated, the anandamide and 2AG are synthesised in the post synaptic neurone. They are then released into the synaptic cleft and bind with the CB receptors which triggers a reduction in neurotransmitter activity.
Put very simply, the endocannabinoid system acts like a controller or fine-tuner of the release of other neurotransmitters. It could be likely that this is an oversimplification however, and that 2AG and anandamide also bind to other receptors but currently the details are unknown.
As soon as anandamide and 2AG have interacted with the receptors, they in turn are broken down by Fatty Acid Amide Hydrolase (FAAH). Therefore, it seems that the endocannabinoids are synthesised and then broken down on demand.
What are the effects of the endocannabinoid system?
The endocannabinoid system seems to have very far-reaching effects. This is unsurprising given the widespread distribution of the cannabinoid receptors throughout the body; with this distribution not simply being limited to the central and peripheral nervous systems.
We know that the endocannabinoid system plays a major role in memory. For instance, it’s clear that phyto-cannabinoids, particularly THC, impair short term memory, so it is hardly surprising that the body’s natural endocannabinoid system has an effect on memory also.
We know that in animal models, a neural growth in the hippocampus can be caused by endocannabinoids. As the hippocampus is part of the limbic system, we know this endocannabinoid action has a particular role to play in memory functions. However, the specific role of the endocannabinoid system in memory is no doubt very complicated.
This is affected by the endocannabinoid system through the modulation of the effects of the other neurotransmitters involved in pain response, for instance the noradrenaline and GABA Ergic system may be impacted.
Daytime drowsiness is an obvious effect of increased endocannabinoid signalling within the central nervous system, which can also induce sleep more generally.
The endocannabinoid system also has an obvious effect in the stimulation of appetite.
In animal studies with mice, when the mice have their CB1 receptor knocked out they are leaner and less hungry than the mice that still have that receptor.
The endocannabinoid system also plays a role in the control of many metabolic functions like nutrient transport and energy storage. The endocannabinoid system may also be involved in modulating insulin sensitivity and therefore may have a role to play in treating clinical conditions like diabetes and obesity (or even atherosclerosis).
We know that the endocannabinoid system plays a role in the modulation of the stress response, especially anxiety behaviour.
There are endocannabinoid receptors found in the bladder and in the male and female reproductive systems.
In the uterus the system may help to regulate the timing of embryonic implantation, with the likelihood of miscarriage perhaps being affected by anandamide levels and whether these are too high or too low.
It now seems that the endocannabinoid system has an essential role to play in embryonic development at both implantation and after birth in the initiation of suckling in the new born baby. Some preliminary research seems to suggest that a reduction in anandamide is necessary for implantation to take place. The initiation of suckling appears to require the activation of CB1 receptors, presumably through the presence of high levels of 2AG1.
With the endocannabinoid system eliciting wide-ranging effects on a variety of bodily functions, It’s not surprising that the use of plant phytocannabinoids that interact with our body’s own endocannabinoid system can have far-reaching effects (both positively and negatively) on a number of aspects of symptom management, human disease and general behaviour.
Further investigation and research into medicinal cannabis and alternative medical options is thoroughly encouraged by The Academy, particularly through the use of our own online courses, evidence base and whitepapers.
The rest of our resources are available on our website. We urge anyone considering use of medical cannabis products to consult with a trained medical professional prior to beginning use.