Complete Guide to the Endocannabinoid System

Tina Magrabi
Tina Magrabi - Content Writer

Nov 26 2021 - 6 min read

Every person – and many animals – has an endocannabinoid system (ECS), a complex network of receptors, lipids, and enzymes that plays a significant role in governing homeostasis and how we individually experience cannabis

While the ECS was identified only in the late 1980s, it quickly became one of the most important scientific discoveries to date. The ECS is involved in sleep, appetite, immune function, and virtually every critical life function. When the endocannabinoid system is out of balance, we are also off-kilter and not functioning at an optimal level. Endocannabinoid deficiencies often precede disease, which is one reason why the system is dubbed “the master regulator.”

Learn exactly how your ECS works and how it impacts your overall health.

Download Free Guide to the ECS

How the Endocannabinoid System Works

The ECS has three main parts: endocannabinoids, receptors, and enzymes. 

Endocannabinoids

Cannabinoids are chemicals in cannabis (and many other plants) that interact with the ECS. Tetrahydrocannabinol (THC), the molecule known for its intoxicating effects, and cannabidiol (CBD), known for promoting relaxation, are some of the more well-known cannabinoids. Still, the cannabis plant contains over 150 different types of these chemicals. 

In addition, the human body generates its own version of cannabinoids that interact with other elements of the ECS, called endocannabinoids. Endocannabinoids are cannabinoids produced by the body, which bind to receptors found in immune cells, throughout the nervous system, up and down the spine, in every brain cell, and even in the skin. 

Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) are primary endocannabinoids. 

Anandamide is the human body’s naturally-occurring THC. Anandamide was discovered in the 1990s and named for the Sanskrit word “ananda,” meaning eternal happiness — it interacts with the body similarly to THC, which induces euphoric highs in many individuals. 

2-AG can have both pain-killing and anti-inflammatory effects. 2-AG is present at relatively high levels in the central nervous system (CNS). 

Receptors

Cannabinoid receptors are found in every cell in the human body, making the ECS work like a mainframe for the central and peripheral nervous systems (CNS and PNS). Cannabinoids and endocannabinoids, therefore, communicate directly or indirectly with a wide range of receptors, including CB1 receptors, CB2 receptors, GPR55 receptors, opioid receptors, dopamine receptors, serotonin receptors, and many more.

Let’s focus on the CB1 and CB2 receptors to get a complete picture of their function. 

CB1 receptors are located most densely in the central nervous system and are mainly responsible for how cannabinoids interact with the brain. Molecules like THC bind to CB1 receptors and cause psychoactive “high” effects.

How exactly do cannabinoids have this effect on brain cells? Well, cannabinoids that bind to CB1 receptors can decrease the release of two proteins called glutamate or GABA (gamma-aminobutyric acid). Glutamate stimulates or excites the nervous system, GABA calms it down. When glutamate levels are high, GABA levels are often low, and vice-versa. 

Simple equation:

Glutamate = go, GABA = stop.

THC blocks the production of GABA. This means that fewer “stop” signals are transmitted and creates a buildup of the “go” signal, glutamate, which can increase the overall amount of dopamine circulating the body, which then causes a psychoactive “high.” 

Here are several other effects that the activation of CB1 receptors causes in the body:

    • It impacts our sense of time
    • Increases our appetite and desire for food
    • Pain-killing or pain-distracting effects
    • Anti-nausea effects
    • An “up” and excited psychoactive effect or a more “down” and relaxing effect associated with THC.

CB2 receptors can be found most densely in the immune system but also on some neurons in the brain, gastrointestinal system, and peripheral nervous system (PNS).

Research implicates CB2 receptors in various functions, including immune suppression, causing apoptosis (cell death), and the induction of cell movement and development. These findings could prove crucial for people with cancerous tumors and precancerous cells. 

Furthermore, CB2 receptor agonists (compounds that activate CB2 receptors) may have significant anti-inflammatory properties that can help treat pain and inflammation. Research has found that targeting CB2 receptors can be helpful for the treatment of autoimmune disorders and arthritis.

Enzymes

The third component of the endocannabinoid system is enzymes that metabolize and break down cannabinoids and endocannabinoids. Two primary enzymes include fatty acid amide hydrolase (FAAH), which breaks down anandamide and THC, and monoacylglycerol lipase (MAGL), responsible for eliminating 2-AG. 

These prevent dangerous endocannabinoids and phytocannabinoids from building up in the body. And yes, the levels of these cannabinoids can be hazardous because the ECS is all about achieving the right balance. 

What Does the ECS Do?

A better question might be, what does the endocannabinoid system NOT do? The ECS is involved in regulating many of life’s most essential processes, including:

    • Reward perception.
    • Reproduction.
    • Inflammatory response.
    • Immune system function.
    • Appetite.
    • Pain sensation.
    • Mood.
    • Memory.
    • The pleasurable effects of exercise.
    • And, of course, mediating the pharmacological and experiential impact of cannabis.

In short, the ECS does a lot more than you might think!

Phytocannabinoids and the Endocannabinoid System

Phytocannabinoids are cannabinoids that the cannabis plant produces. To exert different effects, they bind to endocannabinoids, which your body naturally creates. Two of the most prominent phytocannabinoids in cannabis are THC and CBD. 

THC

THC is an effective painkiller and could also be helpful as an anti-inflammatory, treatment of spasticity, nausea/vomiting, preventative therapy, appetite stimulant, and treatment for an overactive bladder.

Download Free Guide to THC

CBD

CBD may be beneficial as an anti-inflammatory, mood stabilizer, and antispasmodic. This can make CBD helpful for managing chronic pain, anxiety and depression, multiple sclerosis, and epilepsy. 

Download Free Guide to CBD

Other Phytocannabinoids

THC and CBD are just the beginning of the phytocannabinoids that the cannabis plant produces. Other phytocannabinoids like cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN) all offer benefits. Tetrahydrocannabivarin (THCV) is another cannabinoid that has garnered lots of interest, and the terpene beta-caryophyllene is considered a dietary cannabinoid.

Foods with Phytocannabinoids

Enhance your endocannabinoid system by eating some of these tasty foods that contain phytocannabinoids:

    • Chocolate.
    • Veggies like kale and broccoli.
    • Spices like cinnamon and black pepper.

Some of these foods, like black pepper, can help temper a negative experience with cannabis and get your ECS back on track.  

Black peppercorns. Black pepper contains the terpene beta-caryophyllene, which is also in cannabis and is a CB2 receptor agonist.
Black pepper contains beta-caryophyllene, which is also found in cannabis and is a CB2 receptor agonist Beta-caryophyllene is beneficial for treating pain and anxiety. Author: Hubertl. From Wikipedia Commons. CC-BY-SA 4.0.

What Is Clinical Endocannabinoid Deficiency (CED)?

Clinical endocannabinoid deficiency (CED) is a theory posited by Dr. Ethan Russo. Russo explains how many (but not necessarily all) medical conditions coincide with shortages or a dysregulation of the production, metabolism, and amount of endocannabinoids, or a change in the state or condition of cannabinoid receptors. 

This disruption or deficit can come from an injury, infection, an event that triggers long-term inflammatory responses, or genetic dysfunction. Research has connected many medical conditions with a CED, including fibromyalgia, migraine, and irritable bowel disorders (IBDs). Chronic pain, insomnia, anxiety, and depression may also be interlinked symptoms with CED at its root.

Furthermore, autoimmune disorders can cause widespread inflammation in the body, and cannabinoids may help reduce this inflammation. Dravet and Lennox-Gastaut syndromes (two types of epilepsy) could arise due to the lack of genetic coding for a specific cannabinoid that helps regulate calcium and sodium ions.

In theory, one could have an overabundance of cannabinoids as well. A patient named Jo Cameron reportedly lacked the genetic code to produce the enzyme FAAH. This resulted in an overload of anandamide in her system, meaning she hardly felt any pain or anxiety. In general, it is best to have neither deficiencies nor excesses in the ECS, and balance is the key. 

Can Long-Term Cannabis Use Affect the ECS?

There is insufficient evidence to understand how long-term use of cannabis may affect the ECS. Always err on the side of caution when using cannabis or any other drug and consume as directed by your physician. 

How to Strengthen and Heal the ECS

In a word? Balance. The ECS is intimately involved in homeostasis – keeping the body’s physiological processes stable and balanced. You already have the tools to strengthen and heal your own ECS. 

Here are a few simple ways to keep your ECS in top form:

    • Get adequate sleep (seven to nine hours every night)
    • Eat nutritious foods, especially those containing phytocannabinoids (which includes decadent dark chocolate)
    • Exercise, maintain a healthy weight and spend time in the fresh air

These basic lifestyle principles have a tremendous impact on your general health and how good you feel in your everyday life. 

marijuana healthy lifestyle

Frequently Asked Questions

Is the endocannabinoid system real?

Yes, the endocannabinoid system is a real functioning system in your body. Many other mammals also have an ECS, including domestic cats and dogs, and this is one reason why some veterinarians use CBD oil to treat certain conditions in pets. 

Do our bodies produce cannabinoids?

Our bodies naturally produce endocannabinoids, which are cannabinoids made within our ECS. They interact with phytocannabinoids from the cannabis plant to have a synergistic effect. 

How does CBD affect the endocannabinoid system?

CBD helps regulate the ECS in many ways, including a complementary natural treatment for depression and a tool to help manage pain. 

See how medical marijuana can help boost your endocannabinoid system and apply for your MMJ card. The doctors at Leafwell are on-call to guide you through the application process and meet with you in our virtual clinic. 

Written by
Tina Magrabi
Tina Magrabi

Tina Magrabi is a writer and editor specializing in holistic health. She has written hundreds of articles for Weedmaps where she spearheaded the Ailments series on cannabis medicine. In addition, she has written extensively for the women's health blog, SafeBirthProject, as well as print publications including Destinations Magazine and Vero's Voice. Tina is a Yale University alumna and certified yoga instructor with a passion for the outdoors.

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