Your Endocannabinoid System - The Master Regulator of Homeostasis
Given the the importance of balance in a healthy life, it’s important to have at least a basic understanding of the body system that’s responsible for this—the endocannabinoid system (ECS), which has evolved to be the major messaging system for maintaining physiological balance. The scientific term for balance is “homeostasis,” and the ECS is present in all vertebrates (organisms with a spinal cord and vertebrae), not just humans. When an organism is in homeostasis, there is health. If an organism is not in homeostasis, there will be some degree of disease—whether this is experienced by outright clinical symptoms, or subclinically at the cellular level. In these unbalanced situations, if homeostasis can be restored, then diseases should naturally resolve.
As a cellular messaging system, the ECS is all about communication. When cells communicate efficiently, everything works smoothly. If you’re reading this, you probably already know that cannabis is the most obvious therapeutic agent in this endeavour, and it’s especially useful because its phytocannabinoids (plant-based cannabinoids) are structurally similar to the endocannabinoids (the cannabinoids produced within our own bodies). This means that these phytocannabinoids can mimic the actions of our endocannabinoids, such as activating specific receptors located all throughout the body, which are called cannabinoid receptors. Phytocannabinoids are highly therapeutic in situations where it is not possible for the body to make enough endocannabinoids to bring the body back into balance. This is why cannabis is an extremely important and valuable medicine and the scientific, medical, and even political communities are reawakening to this reality after decades of prohibition.
Your Endocannabinoid System
Present in all vertebrates, the endocannabinoid system is a biological messaging system that consists of:
- endocannabinoids (those internally-made cannabinoid compounds),
- enzymes (specialized proteins) that produce or breakdown endocannabinoids, and
- cannabinoid receptors (the target for the endocannabinoids).
These three basic components work together to ultimately to maintain homeostasis in our bodies—with far reaching effects on the major body systems that gives us life and health.
The two primary endocannabinoids are anandamide and 2-AG. There are at least three other known endocannabinoids, but most of the research has been focused on these two main ones. Although these compounds are produced within the body, they have similar chemical structures to the external phytocannabinoids in the cannabis plant. This means that cannabinoids, whether produced by the body or obtained from external sources, will bind to cannabinoid receptors, and result in a biochemical and physiological response.
When the work of these endocannabinoids are done, the body must break them down, and that’s where certain enzymes enter the picture. Anandamide is degraded by fatty acid amide hydrolase (FAAH), whereas 2-AG is degraded by monoacylglycerol lipase (MAGL).
This brings us to the third component of the ECS, the cannabinoid receptors, and what makes all the magic happen. When these receptors are stimulated by either endocannbinoids or phytocannabinoids, a biological response is initiated, resulting in a signaling cascade. These cascades are a series of biochemical reactions, which are ultimately responsible for the effects of cannabinoids.
There are two main cannabinoid receptors: CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2). CB1 is the main receptor in the brain and central nervous system (although it is also found in much lower concentrations throughout the body). This receptor, when activated, is responsible for the psychoactive (mind-altering) effect of tetrahydrocannabinol (THC), the most notorious phytocannabinoid in marijuana.
In the brain, there is an uneven distribution of CB1. The highest concentrations of CB1 are in the:
- basal ganglia, which is involved in coordination of movement
- hippocampus, thought to be the centre of emotion, memory, and the autonomic nervous system
- cerebral cortex, which plays an important role in consciousness
- cerebellum, which functions to coordinate and regulate muscular activity, and
- amygdaloid nucleus, which plays a role in the sense of smell, motivation, and emotions.
One of the key points needing attention here, however, is that cannabinoid receptors are absent from the brainstem. The importance of this is that the brainstem controls breathing, and due to the lack of CB1 receptors, THC cannot affect the function of the brainstem—meaning there is just no way an overdose of cannabis can cause death by stopping respiration. On the other hand, we know that opioids (heroin, morphine, fentanyl, and many other prescription painkillers) can cause death by overdose, and that’s simply because the brainstem contains numerous opioid receptors, and too many opioids will cause breathing to stop.
As for CB2 receptors, they are distributed primarily throughout the immune system (intestines and white blood cells) and the hematopoietic system (blood-making organs, mainly the bone marrow, lymph nodes, and spleen). Smaller quantities are found in the brain, pancreas, and liver.
Activating CB2 receptors is showing to be tremendously therapeutic, and a lot of research activity is taking place in this area. For example, anti-inflammatory activity appears to be one of the main benefits of CB2 activation, but unlike CB1, it does not result in psychoactive effects. This is where beta-caryophyllene (BCP, a major non-intoxicating terpene found in cannabis) enters the picture.
There are a number of other receptor types that are getting more attention from the research community, and given that various endocannabinoids and phytocannabinoids bind to these, there could be a handful of other receptors that get classified as being part of the ECS.
Last point, there are many illnesses and degenerative health conditions linked to a dysfunction in the ECS. In some cases, ECS dysfunction plays a starring role in the disease pathology, yet in others it may just play a minor aggravating role. In any case, keeping this system in tip-top shape is a goal we should all work towards.
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Lee Know is a licensed naturopathic doctor, recipient of several awards, and has held positions as medical advisor, scientific evaluator and director of R&D for major organizations. He’s the author of Mitochondria and the Future of Medicine (Chelsea Green Publishing, 2018) and the VP of Scientific Affairs for Cannanda.
