Cannabis Sativa L. is a plant rich in a series of active ingredients, phytocannabinoids, terpenes and flavonoids, used by man over the centuries for its therapeutic effects.
Precisely from the knowledge of the numerous benefits on the body, in recent decades scientific research has investigated the existence of a pre-established endogenous system (therefore internal to the body), with which the various active ingredients of Cannabis were able to interact.
This led to the discovery of the endocannabinoid system .
The endocannabinoid system (ECS) is a widespread and complex neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and response to endogenous and environmental stimuli. It was identified in the early 90s of the last century by researchers investigating the effect of the molecule of THC (Tetrahydrocannabinol), a compound present in Cannabis. The hypothesis was that cannabinoids could act thanks to their interaction with specific endogenous receptors.
Since then, the endocannabinoid system has been studied in depth: in fact, two different types of receptors have been identified to which cannabinoids and endocannabinoids bind, called CB1 and CB2.
The former are present in both the central and peripheral nervous systems; the latter in the immune cells and in the autonomic system.
This system is identified in mammals, birds, amphibians, fish, sea urchins and molluscs.
But let's take it one step at a time.
How does the endocannabinoid system work?
The endocannabinoid system involves three main components: endocannabinoids, receptors and enzymes.
Endocannabinoids
Endocannabinoids, also called endogenous cannabinoids, are molecules produced by the body. They are similar to cannabinoids or phyto cannabinoids produced by plants, but are generated by your body.
To date, two key endocannabinoids have been identified:
- anandamide (AEA)
- 2-Arachidonoylglycerol (2-AG)
These help maintain a balance of internal functions. Each body produces them as needed, making it difficult to understand what the typical levels are for each.
Endocannabinoid receptors
The identified cannabinoid receptors are CB1 and CB2 and belong to the family of protein-coupled receptors.
The CB1 receptor has been localized in all areas of the brain (cerebellum, hippocampus, olfactory bulb, cerebral cortex, amygdala, hypothalamus), in the medulla, but also in the retina, in the frontal lobe of the pituitary gland, in neuronal and non-neural cells.
Other CB1 receptors have also been identified in peripheral organs and tissues (lungs, heart, spleen, smooth and skeletal muscles, adrenal glands, adipose tissue, skin, eyes, bones, male and female reproductive systems, urinary, cardiovascular and gastrointestinal systems.
CB2 receptors, on the other hand, have been detected predominantly in cells of the immune system, in peripheral tissues and in cells that play a role in the immune response (tonsils, spleen, thymus).
Endocannabinoids can bind to both receptors. The resulting effects depend on where the receptor is located and which endocannabinoid it binds to.
Enzymes
Enzymes are responsible for breaking down endocannabinoids once they have done their job.
The two main enzymes responsible are:
- fatty acid amide hydrolase, which breaks down AEA
- monoacylglycerol acid lipase, which breaks down 2-AG
What are its functions?
The ECS is very complicated and experts have not yet determined exactly how it works or all of its potential functions.
Research so far has linked the ECS to the following processes:
- appetite and digestion
- metabolism
- chronic pain
- inflammation and other immune system responses
- humor
- learning and memory
- motor control
- sleep
- function of the cardiovascular system
- muscle training
- bone remodeling and growth
- liver function
- function of the reproductive system
- fatigue
- skin and nerve function
These functions all contribute to homeostasis, which refers to the stability of your internal environment. For example, if an external force, such as pain from an injury or fever, alters your body's homeostasis, your ECS kicks in to help your body return to its ideal functioning.
What does endocannabinoid deficiency cause?
Some experts believe in a theory known as clinical endocannabinoid deficiency (CECD). This theory suggests that low levels of endocannabinoids in your body or a dysfunction of the ECS can contribute to the development of certain conditions.
A 2016 article reviewing more than 10 years of research on the topic suggests the theory could explain why some people develop migraines, fibromyalgia, and irritable bowel syndrome.
For all of these conditions, the underlying cause is not clear. They are also often resistant to therapies and sometimes occur simultaneously.
As a result, targeting the ECS or endocannabinoid production could be the remedy for treating several conditions.
Sources
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/
Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576607/
Endocannabinoid system and therapeutic cannabis: new perspectives in human and veterinary medicine, by Giorgia della Rocca (Poletto editore, 2019)