How Cannabis Works: The Endocannabinoid System

Learn all about the endocannabinoid system and how cannabis works its magic

What is the Endocannabinoid System?

If you’ve never had a runner’s high, you’ve at least likely heard of it. It’s that euphoric, mood-boosting feeling after running a few miles that’s like being on cloud nine.

While many attribute this effect to endorphins, it’s actually due to the endocannabinoid system releasing endocannabinoids, which influence the brain’s chemistry. In humans, the endocannabinoid system works as a regulator, balancing bodily functions by modulating the central nervous system’s activity to maintain homeostasis.

Homeostasis is when all systems and organs function properly, maintaining the delicate balance between cognitive, physiological, and emotional health.

In a sense, it communicates between the other primary systems including,

  • Central nervous system

  • Cardiovascular system

  • Gastrointestinal system

  • Reproductive system

  • Immunological system

  • Metabolism

The endocannabinoid system works as a nervous system moderator, producing neurotransmitters “on-demand” that influence health and wellness.

What Is The Purpose of the Endocannabinoid System?

The endocannabinoid system helps to activate or deactivate various physiological, cognitive, and emotional functions that often go unnoticed in the body. This includes aspects related to -

  • Appetite

  • Pain response

  • Stress response

  • Inflammatory response

  • Memory and cognition

  • Sleep health

  • Mood

Whenever you feel hungry or not hungry, sleepy or not sleep, or stressed or not stressed, it’s due to how the endocannabinoid system is functioning at that moment.

While we don’t fully understand all of the aspects of how the endocannabinoid system works, we understand that there are three primary components at play.

These are endocannabinoids, cannabinoid receptors, and specialized enzymes.


  • AEA (Anandamide)

  • 2-AG (2-Arachidonoylglycerol)

Endocannabinoid receptors

  • CB1

  • CB2

Specialized enzymes

  • FAAH (Fatty acid amide hydrolase) to metabolize AEA

  • MAGL (Monoacylglycerol lipase) to metabolize 2-AG

Wide Shot of Native Roots grow taken November 2021

What Are Endocannabinoids?

Endocannabinoids are released in response to various internal and external sources, and the body uses them to complete all kinds of functions from digestion to fertility.Endocannabinoids are made or synthesized from within the body’s fat, muscle, and other cellular tissue as needed on-demand to meet an end of some sort, such as activating fight or flight, food-seeking behaviors, or sleep.There are two main endocannabinoids that the body uses to achieve homeostatic regulation, 2-AG, and AEA.AEA, or anandamide, is also known as “the bliss molecule” and it’s used to relax the body, calm the nerves, activate appetite, and more.2-AG is another known endocannabinoid used by the body for functions related to emotion, cognition, energy balance, pain sensation, and neuroinflammation.The ability to produce endocannabinoids is critical to maintaining health and wellness, but they are not the only vital factor at play.

Where Are Endocannabinoids Receptors?

Endocannabinoids such as anandamide achieve their purpose by binding with cannabinoid receptors. There are two primary known cannabinoid receptors, which are aptly called cannabinoid receptors one and two.These receptors are specialized cells that bind with cannabinoids, including the phytocannabinoids found in cannabis.The first cannabinoid receptor (CB1) is primarily centralized in the brain and central nervous system.It’s responsible for mediating aspects related to mood, emotion, and more. Think brain chemistry, cognition, emotion, fight or flight, appetite, etc.The second cannabinoid receptor (CB2) is primarily found around the body’s main organs and appears to be connected with immunological functions such as inflammation, pain response, and others.

Special Enzymes

Once the endocannabinoids and their respective receptors have completed their function, the body uses specialized enzymes that metabolize the endocannabinoids.The enzymes, FAAH and MAGL, live in nerve cells that break endocannabinoids down into their components for future use. The body uses the enzyme FAAH for Anandamide and MAGL to break down 2-AG endocannabinoids.Generally, healthy tone and signaling of endocannabinoids, healthy concentrations of cannabinoid receptor cells, and healthy enzyme function keep the endocannabinoid system functioning properly.However, if any one of these components becomes compromised, malfunctions, or begins to dysfunctional, it will certainly harm health.

Zoomed in image of the cannabis plant help by a Native Roots employee


The active compounds in cannabis are called cannabinoids, and they are nearly identical to the endocannabinoids in our bodies.Cannabinoids from cannabis, such as THC and CBD, also bind with endocannabinoid receptors, helping to augment their activity. In other words, compounds in cannabis support endocannabinoid system signaling.This is why cannabis has properties with a wide array of effects including,

  • Appetite stimulation

  • Stress relief

  • Reduced inflammation

  • Pain relief

  • Sleep health

  • Mood boost

  • Anxiety relief

However, since each person is different, individual responses to cannabis vary. This is why each person has a unique response to cannabis and cannabinoids such as CBD oil.Since the endocannabinoid system influences so many different aspects of wellness, and each person is different, no two people will have the same experience, even from the same dosage of cannabinoids.


Depending on the circumstances and dosage, in small amounts CBD can have a stimulating and energized, focusing effect from elevated endocannabinoid levels.CBD also helps to lower levels of cortisol in the body. Also known as the stress hormone, cortisol keeps the body alert and primed for action. But it can also keep you from falling asleep, reduce appetite, and suppress the healthy functions of the immune system.However, in larger doses, CBD may have a more sedative-like effect that can induce relaxation, reduce inflammation, and improve mood and aspects of pain.CBD, or cannabidiol, doesn’t have an affinity for binding with CB1 receptors in the brain, which is why it doesn’t have a psychoactive effect as does THC.CBD is primarily known to bind with CB2 receptors located throughout the body, and generally has a calming effect on the nervous system.


THC, or delta-9 tetrahydrocannabinol, is the main psychoactive compound in cannabis responsible for the high from using cannabis.Since THC and AEA both activate CB1 receptor activity, they also trigger many of the same physiological responses such as improved mood, pain relief, relaxation, increased appetite, and feeling sleepy or drowsy.THC’s affinity for binding with CB1 receptors in the brain is also the reason for its psychoactive properties that give the user an altered sense of perception.


Understanding how cannabis works to enhance endocannabinoid functions can help you optimize your experience with cannabis.Learning how to pick different cannabis profiles and cannabis strains can help you get the most out of cannabis, especially if you are interested in specific effects and outcomes such as improved appetite, sleep, stress, or pain.Enjoying cannabis isn’t only about having fun and getting high, it’s also about improving the quality of your life and enhancing experiences with ourselves and with others.