The Endocannabinoid System

The endocannabinoid system, named after the plant that led to its discovery, is the universal, omnipresent system of internal regulation, cellular communication and homeostasis. It plays a very important role in establishing and maintaining human health. It is present in humans, animals and plants alike, except insects. It is believed that this system appeared about 500 million years ago and kept on evolving¹.

The discovery of this system was a result of significant research since 1964.That year, famous Israeli scientist Professor Mechoulam, and his team isolated THC, Δ⁹-Tetrahydrocannabinol, the most abundant part of cannabis responsible for its psychoactive effects, feeling of euphoria and sedation².

This discovery opened the doors to a better understanding of how our body and brain function. Further research led to the isolation of over 100s of other cannabinoids and the most famous cannabinoid, cannabidiol also known as CBD. In comparison to THC, CBD is the second most abundant, non-psychoactive part of the cannabis plant³.

In the 1990s, researchers cloned cannabinoid receptors that are present throughout the human body, these are CB1 and CB2 receptiors.

CB1 receptors, mostly found in the central nervous system².

CB2 receptors mostly found in the immune system and its associated structures².

Following the discoveries of exogenous, plant cannabinoids, scientists isolated endogenous cannabinoids also known as endocannabinoids: anandamide and 2-AG. These molecules are naturally produced in human bodies. Both endocannabinoids and THC are similar in molecular structure and interact with cannabinoid receptors, based on key and lock analogy¹.

The endocannabinoid system consists of three major components^1,2,4.

• The cannabinoid receptors: CB1 and CB2
• The endocannabinoids: anandamide and 2-AG, that interact with these receptors
• The enzymes which are involved in synthesis and degradation of these endocannabinoids: Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL)

This system is involved in the regulation of many physiological processes including¹:

In short, its role can be described as controlling eat, sleep, relax, forget, and protect functions5. These basic functions of the endocannabinoid system were summarized in 1998 by Professor Di Marzo.

Endocannabinoid system in action explained

1. Action potential reaches presynaptic neuron
2. This opens calcium channels
3. Calcium influx triggers release of neurotransmitters stored in presynaptic vesicles
4. Neurotransmitters travel across the synaptic cleft and activate postsynaptic receptors
5. Upregulated neurotransmitters cause calcium release in postsynaptic neuron
6. This leads to endocannabinoid synthesis, which travel retrograde to the presynaptic neuron
7. These endocannabinoids interact with CB1 receptors
8. This closes presynaptic calcium channels and stops neurotransmitter release
9. 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.