Posted by Joshua Standifer & Luis N. Pacheco, MD, FAAFP on 5th Aug 2019

Stress, digestion, inflammation & pain - meet the system that keeps them balanced. 

Chances are you've never heard of the Endocannabinoid System. Endo means "occurring within the body," while the canna in cannabinoid refers to the hemp plant that led to its discovery. It's a recent addition, as far as human systems go. Even more surprising is the vastness of its involvement in stress regulation both inside and outside of your body.

The Endocannabinoid System (ECS) evolved in invertebrate species as early as 600 million years ago as a means of regulating the stress of an organism within its environment. Imagine it like the thermostat that measures the temperature of your car's engine--only the thermostat of your ECS has thousands of functions. Back in prehistory, when it got too hot or cold, when there was less food or water, or when the body became imbalanced, inflamed, or injured, the Endocannabinoid System evolved to kick on. Beyond the simple function of a thermostat, however, your Endocannabinoid System developed finely tuned response relationships with your bones, brain, cells, organs, nervous system, glands, and most-importantly: your immune system.

For years Western Science wasn't sure exactly how hemp and its compounds affected the body. It was in 1988 at the St. Louis University School of Medicine that Allyn Howlett and William Devane first discovered the Endocannabinoid receptor sites in the mammalian brain. These sites responded exclusively to hemp compounds, and were more prevalent than any other receptor system in the brain.

Which begged the question...

Why do we have so many ECS receptors?

The reason your body has so many ECS receptor sites is the same reason the power grid is spread across our country. Your Endocannabinoid System functions like the telephone poles, transformers, towers, energy generators, and repair workers that combine their resources to distribute electricity to downtown skyscrapers along with distant cabins in the wilderness. The energy network doesn't care where or what it's feeding power to. It was designed to make that power accessible and distribute it where it needs to go.

These distribution outlets come in the form of receptor sites. Your cannabinoid receptors are designed by nature to react to cannabinoids.These fatty neurotransmitters fit like little plugs into the outlets of your ECS receptors. Your ECS uses cannabinoids to moderate your body's functions the same way a team of technicians watches the sensors and screens at a power plant. If there's a power outage in one area of the network, it sends more cannabinoids to the area to restore balance and get things running smoothly.

Your receptors come in two different forms: CB1 (predominantly brain) and CB2 (predominantly elsewhere). Just like the job of a power grid is to keep the lights on, the job of your natural healing network is to restore the balance.

What does Science have to say about your ECS?

Science is just beginning to shine light on the how critical a healthy ECS is to both young and old people alike. It helps aid digestion, thought, stress, mood, learning, sleep, pain, and inflammation--but that might only be the beginning. The more they research, the more they find. This is one of the main reasons the Endocannabinoid System has been targeted for its role in therapeutic applications (1). By designing compounds that can interact with the ECS in animals and humans, scientists hope to help relieve some health complications associated with dysfunction in these areas. The chart below shows only a few locations of your ECS receptors.

Location and Function of CB1 and CB2 Receptors.

These statements and images have not been approved by the FDA, and are for educational purposes only. (2)

Science seems to be telling us that a healthy ECS is indispensable in the regulation of brain, endocrine, and immune tissue function (3). Brain function refers to your command center, managing the screens, sensors, and levers of your body. The Endocrine System is a group of glands that secrete hormones into the Circulatory System to regulate the activity of your cells, organs, body growth, sexual function and metabolism, ensuring those systems work together. Immune tissues involve the Lymphatic System. This is composed of lymph nodes, white blood cells, bone marrow lymphocytes, the thymus, and the spleen, and comprises the clean-up crew of your immune system.

That's quite a job for one system. So how did science reach that conclusion? And what does CBD have to do with any of it?

Here's a streamline of the discoveries leading to the ECS, so we can get to the good stuff: *

  • 1963 - phytocannabinoids are elucidated by Dr. Raphael Mechoulam. *
  • 1988 - Howlett and Devane discover the Endocannabinoid receptors (CB1 and, later, CB2). *
  • 1990 - Lisa Matsuda et al. maps the DNA of Endocannabinoid brain sequence (leading to the further elucidation of the ECS structure). *
  • 1992 - Hanus and Devane discover the presence of the naturally occurring cannabinoid, the neurotransmitter Anandamide (known as the bliss molecule). This leads to the later discoveries of the second most populous endocannabinoid, 2-AG, and a string of lesser known cannabinoids, HGLE, DEA, and 2-AGE. *
  • 2005 - Pertwee, Howlett, et al. bring cumulative studies across the years to support a better understanding and map of the ECS, its functions, its impacts on the body, and its role in analgesia (the regulation of pain), anti-inflammatory signaling, and immune function.

A critical piece of clockwork in the human body had been revealed, and with it, the discovery that certain compounds might increase or decrease the efficiency of the Endocannabinoid System. It has become widely accepted that the job of your Endocannabinoid System is to regulate the release of endocannabinoids to perform various balancing functions within your brain and body.

Think of it this way.

"Endocannabinoids are key modulators of emotions, and altered endocannabinoid signalling has been implicated in several psychiatric disorders. [ ] Cannabinoids have been implicated in aspects of emotion, motivation and learning." (4)

It soon became clear that various health issues might be connected to a malfunctioning ECS. Science set their eyes on discovering the culprit. In 1993 they identified the fatty acid Amide Hydrolase: FAAH. FAAH degrades the fatty neurotransmitters used by the Endocannabinoid System to do its work. If left unchecked, this can lead to Clinical Endocannabinoid Deficiency.

Some studies propose that this deficiency could underlie migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions (5). Though a deficiency can come from other issues, a leading hypothesis for its widespread impact could be improper support of the Endocannabinoid System. This critical network can degrade with the combined stressors of living and aging. Over time the lights along the power grid can start to stutter, resulting in energy loss, sleep irregularity, mood shifts, and inflammatory imbalances.

The wellness of CBD

CBD is also a cannabinoid, which means it behaves in the body similarly. CBD is a phytocannabinoid from plants, while compounds like Anandamide and 2-AGE are cannabinoid neurotransmitters. Due to their similar molecular structure, they could interact supportively with your Endocannabinoid System.

Additionally, CBD could hold promise as a powerful anti-inflammatory, taking stress off of the ECS so it doesn't exhaust itself (6). Plant cannabinoids such as CBD appear to strongly reduce symptoms in animal models of visceral, acute, inflammatory, and chronic pain (7). CBD does not produce euphoria or intoxication (8). Furthermore - and this a BIG furthermore - biochemical studies indicate cannabidiol could support your body's cannabinoids (9) by inhibiting the production of the fatty-acid FAAH. By limiting the production of FAAH, the ECS could be freed to use its own replenished cannabinoids for the job they were designed to perform.

"Modulating the activity of the Endocannabinoid System turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders [], neuropathic pain, multiple sclerosis and spinal cord injury, to [ ] atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few." (10)

In conclusion, the Endocannabinoid System is a natural healing network that functions like a power grid, distributing the energy of cannabinoids to assist the balance of mood, digestion, sleep, pain, inflammation, memory, and many other functions. This system can degrade over time, which could contribute to a wide array of issues and complications. A healthy Endocannabinoid System is critical for optimal wellness. Supporting the health of your Endocannabinoid System could enable it to function as nature intended.


  1. https://www.ncbi.nlm.nih.gov/pubmed/17369778
  2. https://www.ncbi.nlm.nih.gov/pubmed/30553404
  3. https://www.ncbi.nlm.nih.gov/pubmed/30553404
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC34968...
  5. https://www.ncbi.nlm.nih.gov/pubmed/15159679
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33824...
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33824...
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33824...
  9. https://www.nature.com/articles/tp201215
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC22417...
*These statements and images have not been approved by the FDA, are not intended to diagnose, treat, prevent, or cure any condition or disease, and are for educational purposes only.