What is the endocannabinoid system? There are many articles about it now. However, they are quite often difficult to understand to general public. Not everyone is a scientist or a doctor.
My aim here is to explain it in a very easy to understand and follow manner, discussing what led to the discovery of this very important system. I did struggle with the concept myself when I started to study cannabis.
The discovery of THC (psychoactive part of cannabis) in 1964 by prof. Mechoulan and his team opened the door to further research on other active molecules in cannabis plant called cannabinoids, among them most famous CBD, non-psychoactive, non- toxic and highly therapeutic.
Then in 1991 scientists cloned the receptor called CB1. This receptor is present mostly in our brain and is activated by THC. 1993 brought the discovery of anandamide, our own cannabinoid or endocannabinoid because it is made by our bodies, some call it our own internal marihuana but this is not very accurate. The second receptor CB2 was also cloned this year. This receptor is mostly present in our immune system and is activated by THC as well.
In 1995 the second endocannabinoid 2-AG, which stands for arachidonoylglycerol was discovered. So, in the 90s, a very important system was discovered, the Endocannabinoid System(ECS).
ECS is a physiological, universal system of regulation, cellular communication and homeostasis. It is widely present in humans, animals and plants except insects. It is involved in many biochemical reactions that constantly take place in our bodies.
Its role can be summarised in following simple statements. Eat, sleep, relax, protect and forget.
This important system consists of
- CB1 and CB2 receptors
- Endocannabinoids-anandamide and 2-AG , which activate these receptors
- Enzymes , which metabolise these receptors after particular physiological reaction is completed.
Endocannabinoids as well as plant cannabinoids, mostly THC bind to CB1 and CB2 receptors based on a key and lock analogy. CBD has weak affinity to these receptors and modulates the psychoactive effects of THC.
CBD effects many biochemical pathways in our bodies. When cannabinoids bind to these receptors, two things might occur:
- particular biochemical reaction will follow and this is called agonistic reaction.
- particular biochemical reaction is blocked and this is called antagonistic reaction.
ECS works like the thermostat, switching the biochemical reactions on and off depending on the need as our bodies constantly strive for homeostasis.
The ECS In Action
Endocannabinoid system in action explained
- Action potential reaches presynaptic neuron
- This opens calcium channels
- Calcium influx triggers release of neurotransmitters stored in presynaptic vesicles
- Neurotransmitters travel across the synaptic cleft and activate postsynaptic receptors
- Upregulated neurotransmitters cause calcium release in postsynaptic neuron
- This leads to endocannabinoid synthesis, which travel retrograde to the presynaptic neuron
- These endocannabinoids interact with CB1 receptors
- This closes presynaptic calcium channels and stops neurotransmitter release
- Cannabinoids are degraded by FAAH and MAGL on completion of this process
The overall process is more complicated, this is just a simple explanation of the ECS in action to convey it’s core functions. In summary, the ECS works to maintain homeostasis.