How Your Endocannabinoid System Works

Cannabis works because of your endogenous cannabinoid system, also called the endocannabinoid system or the ECS for short. While researchers continue to discover precisely how deep this connection goes, we know that your experience with cannabis is the direct result of how compounds within the plant interact with this system. 

What is the endocannabinoid system?

The endocannabinoid system is a widespread system that influences many bodily functions, such as appetite or pain¹. It was first identified in 1992 by famed cannabis researcher Dr. Raphael Mechoulam along with researchers William Devane and Dr. Lumir Hanus. This widespread network of compounds and receptors is not just in humans, but present in all mammals.

This system exists throughout your brain, skin, nervous system, and more. Phytocannabinoids and endocannabinoids interact with these receptors, assisting to keep your body in a state of homeostasis, or its normal state of being. When something feels “off” or has gone awry in your body, your ECS is believed to play a role in returning things back to normal.  

Two types of receptors have been identified: CB₁ receptors and CB₂ receptors:

• CB₁ receptors: Prevalent in the central nervous system, CB₁ receptors are found primarily in parts of your brain like the cortex, basal ganglia, hippocampus, and cerebellum. They are believed to play a role in modulating the release of neurotransmitters², which could have wide ranging effects on sleep, appetite, motivation, and mood, among others.

• CB₂ receptors: CB₂ receptors are less common in the central nervous system, instead appearing primarily in parts of the body associated with the immune system³.

Your body naturally produces endocannabinoids, which interact with these receptors. These endocannabinoids are broken down by enzymes after they have carried out their function, only to be recycled and released once more when needed. The two most prevalent and well-researched endocannabinoids are anandamide and 2- arachidonoyl glycerol (2-AG):

• Anandamide: Also called the “bliss molecule,” anandamide primarily interacts with CB₁ receptors. It’s thought to influence your appetite, motivation, and sleep patterns⁴.
  
• 2-AG: 2-AG interacts with CB₁ and CB₂ receptors. It is present at especially high levels in the central nervous system⁵.

Additional endocannabinoids include compounds called virodhamine and 2-AG ether. However, these endocannabinoids have not been studied as extensively as anandamide and 2-AG. 

How does cannabis influence the ECS?

Cannabis is home to more than 100 phytocannabinoids, or cannabinoids sourced from plants. The most well known phytocannabinoid, Tetrahydrocannabinol (THC), interacts with the CB₁ receptor in your ECS⁶, while its non-intoxicating cousin, Cannabidiol (CBD), modulates CB₁ receptors.

While research into the precise nature of the endocannabinoid system remains ongoing⁷, many promising observations have already been made. For example, the endocannabinoid system is thought to be responsible for regulating pain and inflammation. Cannabinoids could hold promise for chronic pain management due to the way they interact with cannabinoid receptors⁸. 

Other observations of phytocannabinoid interaction with the endocannabinoid system include:

• THC has been observed to bind to CB₁ receptors⁹. In addition to its potential for pain management, it is also thought to stimulate appetite and could influence stress responses. It is also the cannabinoid responsible for producing the intoxicating effects associated with consumption.
  
• CBD binds indirectly to the CB1 receptor, acting as a modulator to the THC binding site and reducing the intoxicating effects of THC. Some research also suggests that CBD increases the action of natural or endogenous cannabinoids by preventing them from being removed from the site of action and broken down¹⁰. As researchers continue to observe CBD’s influence on a range of functions like pain, nausea, and appetite, the exact nature of its interaction with the endocannabinoid system is still being studied.
  
• Cannabigerol (CBG), also known as the “mother of all cannabinoids,” is the precursor for all other cannabinoids in the cannabis plant. We currently have no conclusive evidence for how CBG interacts with the ECS. Researchers are studying CBG’s effects on balancing mood and helping with stress.
  
  

How do cannabinoids relate to the entourage effect?

Researchers are exploring whether it’s more beneficial to isolate a cannabinoid and consume it on its own, or to consume the full range of cannabinoids, terpenes, and other compounds found in the cannabis plant. The latter is called the entourage effect, when two or more compounds work together to enhance the total effect of all the involved compounds. Therefore, the theory suggests that cannabinoids — along with terpenes and the many other compounds found in cannabis — work best when taken together.

Researchers have uncovered some evidence in support of the entourage effect and cannabinoids. A 2010 trial using cannabis extracts in patients with chronic pain found that a THC extract performed poorly against a placebo group, while a THC/CBD extract performed significantly better than both groups¹¹. Similarly, a 2018 study of human breast cancer cell lines showed that a cannabis extract treatment containing THC with small concentrations of CBG and THCA was more effective than a pure THC extract¹². However, the entourage effect is still a topic of debate in the scientific community. A lack of double-blind clinical trials have led many researchers to dismiss the most common evidence as anecdotal¹³. 

Expanding our understanding of cannabis through the ECS 

While cannabis use is nothing new, the system it influences is a relatively new discovery. Scientific and medical communities are learning more about the ECS every day. As cannabis laws around the world are gradually relaxed, new research into cannabis and its impact on the endocannabinoid system can flourish. 

As we learn more about how cannabis affects our bodies, we at Ethos believe it’s of the utmost importance to share this information with our customers. We are committed to ongoing education as the newest science develops. We want you to fully understand not just which cannabis products are right for you, but how they work and ultimately help you feel better. Wherever you are on your cannabis journey, we are grateful to be able to guide and support you.

Sources

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789136/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192322/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062638/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751
5. https://pubmed.ncbi.nlm.nih.gov/9915812/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820295/
9. https://www.healthline.com/health/endocannabinoid-system#thc
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604182/pdf/13311_2015_Article_377.pdf
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334252/#B35
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334252/#B6
13. https://www.scientificamerican.com/article/some-of-the-parts-is-marijuana-rsquo-s-ldquo-entourage-effect-rdquo-scientifically-valid/