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The History Of The Endocannabinoid System

In recent years, CBD has taken the wellness world by storm. Research surrounding its use has been growing over the last few decades, supporting its use as a natural pain reliever, anxiety reducer, inflammation reliever, and so much more.

All of this stems from CBD’s ability to interact with the endocannabinoid system, or ECS - your body’s internal regulating system. As we learn more about the ECS and how it works, natural solutions (like CBD) for harnessing its potential become more well understood and validated as natural alternatives to other, more invasive, or dangerous medical interventions.

Today, we’re going to talk about the history of the endocannabinoid system – how it was discovered, and how it’s been studied since then. The ECS is the unifying reason as to why and how CBD can exert its beneficial effects in so many different ways.

How The Endocannabinoid System Was Discovered

The first big jump in research surrounding the ECS was during an animal study. A team of scientists at St. Louis University Medical School discovered that rat’s brains had receptors – protein molecules embedded in cell membranes – that were activated by CBD’s better-known cousin, THC.

THC is a compound that is found in cannabis plants. This is how THC is often confused with CBD; they come from the same type of plant, but they are completely different. Unlike CBD, THC has a psychoactive effect - and is the compound found in marijuana that is responsible for users’ “highs.” CBD has absolutely no psychoactive effects.

The receptor that these scientists discovered during their 1988 study was named “CB1.” Later, it was discovered that CB1 receptors were highly abundant in mammal brains – including human brains. At this point, the search was on for compounds that could attach to the CB1 receptor.

How Endocannabinoids Were Discovered

Endocannabinoids are the human body-made compounds that bind to receptors within your endocannabinoid system. 

CBD is a phytocannabinoid. It mimics the effects of our own endocannabinoids by binding to the same receptor groups and exerting the same effects. In 1992, N-arachidonoylethanolamide, more commonly known as “anandamide,” was discovered by a team of scientists. 

They discovered that this endocannabinoid was able to bind to CB1 receptors in neurotransmitters within pig brain tissue.

CB1 receptors impact bodily functions such as appetite, mood, metabolism, pain perception, and more. 

While these scientists discovered that anandamide isn’t molecularly similar to THC, they discovered that like THC, it was able to effectively bind to CB1 receptors to exert its particular effects. For example – high levels of anandamide are essential for sparking processes such as ovulation.

CB2 Receptors

In 1993, scientists discovered a second type of cannabinoid receptor, which they dubbed “CB2.” This receptor is found throughout the immune system, peripheral nervous system, and many internal organs.

This receptor largely plays a role in signaling inflammation. The study shed light on how engaging CB2 receptors in a therapeutic way could assist in regulating inflammation levels. 

It was discovered that an over- or under-abundance of CB2 signaling could cause issues such as peripheral neuropathy, insulin resistance (diabetes) liver disease, and other inflammatory or autoimmune illnesses.

Understanding How The ECS Plays A Role In Disease

In 2004, Dr. Ethan Russo, a neurologist, coined the phrase “clinical endocannabinoid deficiency.” In his research, he hypothesized that endocannabinoid function can cause many types of illnesses and diseases – particularly migraines, IBS, clinical depression, and fibromyalgia.

He hypothesized that patients who experience such illnesses are deficient in certain cannabinoids. Studies that followed would further link endocannabinoid deficiencies to other diseases and problems, such as PTSD, autism, epilepsy, and other neurodegenerative conditions.

There are several factors that can contribute to endocannabinoid dysfunction. Sometimes, it’s caused by genetics. But lifestyle factors can predispose patients to certain endocannabinoid-related diseases and conditions. Things like lack of exercise, poor diet, etc., can cause chronic stress.

It’s been discovered that chronic stress can impact the ECS, leading to prolonged chronic inflammation, elevated cortisol levels, hormone imbalances, and immune dysfunction.

The ECS And Mitochondria

In 2012, a team of French scientists discovered CB1 receptors on the membranes of mitochondria. Mitochondria are the energy-generating “engine” of all cells.

This discovery showed that the function of the ECS impacts more than just a select few bodily processes – if there are receptors within mitochondria, which exist in every cell of your body, the endocannabinoid system regulates mitochondrial activity.

When mitochondria create energy, they release free radicals. Some amount of free radicals are normal, but when they outnumber antioxidants, which neutralize free radicals, this creates oxidative stress. Free radicals are unpaired electrons – and when they search for electrons to which they might bind, they can damage surrounding cells.

Using cannabinoids like CBD to regulate oxidative stress can, therefore, assist in preventing the inflammation and cell damage caused by oxidative stress. CBD is known to have more antioxidants than Vitamin C or E. 

As research surrounding the endocannabinoid system continues to grow, we are beginning to understand just how many benefits CBD, and cannabinoids like it, can have on improving your overall health.


Dr. Meredith Warner is the creator of Well Theory and The Healing Sole. She is a board-certified Orthopedic Surgeon and Air Force Veteran.

She is on a mission to disrupt traditional medicine practices and promote betterment physically, spiritually and mentally to many more people. She advocates for wellness and functional health over big pharma so more people can age vibrantly with more function and less pain.

At Well Theory, Our surgeon-designed products are FDA Registered and formulated to help people:

  • Manage the symptoms of musculoskeletal pain
  • Recover vibrantly from orthopedic related surgeries
  • Fill the gaps in our daily diets
  • Manage pain associated with inflammation

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