The human body contains an endogenous cannabinoid system, commonly referred to as the endocannabinoid system, or ECS for short. The ECS is a widespread neuromodulatory system with far reaching affects throughout the whole body, from the Central Nervous System (CNS) to the Periphery. The ECS regulates the human body and is involved in cellular processes such as apoptosis (cell death), carcinogenesis (cancer formation), the regulation of pain, hunger, satiety, feeding and metabolism, and emotional memory.

The ECS is comprised of 3 main components:

  1. Cannabinoid receptors (CB1 and CB2)
  2. Endocannabinoids (2-AG and AEA)
  3. Enzymes (FAAH and MAGL)

 

A) Cannabinoid Receptors:

The ECS is made up of 2 main receptors; CB1 and CB2, which are present all throughout the brain and body. CB1 receptors are primarily in the CNS, while CB2 receptors are primarily in the periphery. When these cannabinoid receptors are activated by the endocannabinoids, it elicits a therapeutic effect. Endocannabinoids, 2-AG and Anandamide (or AEA), are produced naturally by the body on an as-needed basis (we’ll explain below). The cannabinoids found in the cannabis plant are very similar to these endogenous cannabinoids and can bind to these same receptors.

When cannabis is consumed, select phytocannabinoids (plant compounds) bind to CB1 receptors in the brain, and work to reduce anxiety. When CB2 receptors are activated, it can address inflammatory conditions and help modulate the immune system response. We call this affinity of cannabinoids binding to its receptors, the lock & key mechanism. Think of CB1 and CB2 receptors as locks within your body, and the keys are the naturally occurring endocannabinoids in our ECS + phytocannabinoids within the plant.

The most popular and well-studied phytocannabinoid called cannabidiol (or CBD), however, doesn’t fit into either CB1 or CB2 receptors. Instead, it activates other receptors in the body which stimulate the ECS indirectly. In fact, studies suggest CBD can activate multiple different pathways at once, which could contribute to the reason why it can have different affects and help with different ailments.

B) Endocannabinoids:

The 2 of most well studied endocannabinoids are 2-AG and AEA. These compounds are endogenous agonists of the receptors to which delta-9-tetrahydrocannabinoil (THC) also binds. They are derived from arachidonic acid produced by the body. 2-AG and AEA target the 2 different cannabinoid receptors (CB1 and CB2), aforementioned. AEA, or anandamide, is an essential fatty acid neurotransmitter that plays a role in human behavior and emotions. It is a partial agonist of CB1 receptors and TRPV1 receptors, with low affinity and efficacy at CB2 receptors. AEA is commonly known as the “bliss molecule.” When we’re feeling down, or depressed, it’s often attributed to inflammation or lack of AEA neurotransmitter signaling caused by a distressed endocannabinoid tone. AEA works to decrease the inflammation and increase neuron signaling to boot our mood.

C) Enzymes:

The 2 major enzymes (FAAH and MAGL) are responsible for the synthesis and degradation of endocannabinoids. Phytocannabinoids like CBD can affect overall levels of endocannabinoids in the brain by influencing enzymes as followed:

  1. CBD inhibits the FAAH enzyme, which breaks down Anandamide, or AEA, or the Bliss molecule we just mentioned. Essentially, CBD can increase Anandamide levels by preventing FAAH from breaking it down.
  2. CBD inhibits the MAGL enzyme, which results in increase levels of 2-AG. The upkick of brain 2-AG can influence you to essentially help you feel less stressed and anxious.

Evidently, the ECS is a complex network of checks and balances in our body. It modulates our body’s functions by using receptors CB1 and CB2 that are affected by cannabinoids—either made from the body (endocannabinoids) or taken exogenously from the plant (phytocannabinoids). Scientists have identified at least 113 cannabinoids in the cannabis plant, and over 200 terpenes. There is still so much to learn about the other cannabinoids, aside from CBD and THC. Cannabis should be considered a superfood, given all the beneficial compounds it contains; and as an active drug, with all the potential therapeutic benefits it has on our body.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC15753333/

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1748-1716.2011.02280.x

 

 

 

 

 

 

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