The Endocannabanoid System: CBD, THC, What is the difference?

Updated: Apr 21

by Dr. Mitchell Rasmussen, DC, CFMP, FRC-ms


We have previously discussed how we implement Rightful into our practice. It serves as a helpful bridge between the Physical and Functional Medicine components of our multi-discipline wellness clinic. Its powerful and well-rounded ingredient list covers a lot of foundational “bases” when it comes to some of the biggest challenges we find in our patient population:

A- Stress*

B- Sleep Issues

C- Chronic Pain

D- Mood Disorders

At the root of all of these is typically some manner of CHRONIC SYSTEMIC INFLAMMATION. This is a common thread to the abovementioned conditions; and is a common thread to nearly everything we suffer with relating to our health.

*To see a previous discussion about the adaptogens in Rightful, and to read a bit about why adaptogens are so vital to our stress response see this post.



Some science regarding CBD and the Endocannabinoid System (ECS)


The ECS is a complex signaling system which involves three core components (endocannabinoids, receptors, and enzymes). Endocannabinoid receptors are found throughout the body, and there are two main receptors within the ECS.


  1. CB1 receptors: Located mostly within the brain and spinal cord.

  2. CB2 receptors: Located mostly in the periphery, ESPECIALLY IMMUNE CELLS. Additionally, located in some neurons.

  3. Maybe as yet to be determined other CB receptors.

CB2 receptors have been found in natural killer cells, macrophages, lymphocytes, the spleen, thymus, lymph nodes, and tonsils. All of these are critical to our coordinated immune response.

A 2010 paper from Expert Reviews in Molecular Medicine had this to say about exogenous cannabinoid research; as well as its likely CB2 receptor ‘magic’:

“Collectively, the results from a number of studies suggest that exogenous cannabinoids elicit a shift in the cytokine expression profile from that which is Th1 proinflammatory to one that is Th2 anti-inflammatory and that the CB2 may be linked to this effect.”

Bottomline: Experts today believe that maintaining homeostasis is a PRIMARY role of the ECS, and that with its complex actions in our immune and nervous systems, as well as virtually all of the body’s organs, the ECS is quite literally a bridge between the mind and the body.


Interestingly, the cannabinoids our body naturally produces (endocannabinoids) can bind to either receptor, and effects depend on where the receptor is located and which endocannabinoid it binds to. These endocannabinoids are similar in structure to cannabinoids, except that they are produced by the body, as stated.


How might an endocannabinoid act? For example, it might bind on CB1 receptors in a spinal nerve. The result is pain relief. That is awesome.

Additionally; many of the psychoactive effects of cannabinoids are mediated through the CB1 receptor.

What if a CB2 receptor is targeted? Endocannabinoids can bind here on an immune cell. This signals that you are experiencing inflammation. Inflammation is a hallmark sign of pretty much anything we suffer with chronically.


New insights are constantly being provided thanks to ongoing studies aimed at discerning signaling events as a result of CB2 receptor binding, as well as the role of exogenous cannabinoids (meaning, that we ingest CBD) in finding and maintaining homeostatic immune balance. Studies are suggesting that CB2 may serve as an ideal molecular target for therapeutic correction of immune dysregulation, especially immune dysregulation associated with a hyperinflammatory component. [Back to this “inflammation”. Always. And forever more.]

Research is continually needed in this field, and the ECS is a complicated system. Even though experts haven’t yet determined exactly how the ECS works,

research has linked the ECS to the following:

Appetite/digestion

Metabolism

Chronic pain

Inflammation, and other immune responses

Sleep

Mood

Learning/memory

Muscle formation

Liver function

Stress

Motor control

Reproductive system function

Bone remodeling/growth

Skin

Nerve function

"Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation.

In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated."

CANNABINOIDS


There are three main exogenous cannabinoids typically considered for study:


  1. Delta-9-tetrahydrocannabinol (THC) – Legal in Colorado. Maybe not legal in your area.

  2. Cannabidiol (CBD)

  3. Cannabinol (CBN)



Tetrahydrocannabinol (THC) is one of the main cannabinoids found in cannabis. It is typically thought of as the component that renders a user “high”.

THC is a major psychoactive and immunomodulatory component in marijuana. Specifically; immune cells at peripheral sites and within the Central Nervous System.


Once THC gets into the body, it binds to both CB1 AND CB2 receptors. This is responsible for the large variety of potential effects from use. Some of these may be desirable, and others potentially not so much.

THC binding to CB1 receptors overstimulates them. This causes the “high”.

THC can help reduce pain, as well as stimulate appetite. On the flip side, it can also trigger paranoia and anxiety in many cases.


New frontiers in medical research have recently been aimed at elucidating ways to produce synthetic THC cannabinoids to interact with the ECS in only beneficial ways.


One potential issue with THC and the immune system is in its potential to decrease resistance to a certain bacterium, Listeria monocytogenes, as well as Herpes Simplex virus-2. This is the virus that typically causes the common condition, “cold sore”. More research is warranted with regard to other potential negative effects of THC.

Cannabidiol (CBD) is another major cannabinoid found in cannabis. It is the second most prevalent active ingredient. The Hemp plant also contains CBD. Unlike with THC, CBD doesn’t make you “high”.


Additionally, we typically don’t see ANY negative effects from CBD ingestion.

CBD is interesting in that it DOES NOT bind to CB1 or CB2 receptors the way THC does.


It appears that CBD doesn’t bind directly to the receptors at all; instead it acts indirectly. These indirect actions work on receptors associated with pain perception as well as inflammation.


Many experts in this field believe that CBD probably works by preventing endocannabinoids (the ones our bodies produce naturally) from being broken down.


It could be an enzyme CBD affects in this way to prevent breakdown. Others believe that CBD may bind to a receptor not yet discovered and identified.

Fun Fact: CBD inhibits an enzyme, Fatty Acid Amide Hydrolase, which leads to higher levels of an endocannabinoid known as Anandamide. You might have heard of this referred to as the ‘bliss molecule’. Anandamide plays roles in pleasure and motivation at the neurological level.

In addition to the common reasons we might use CBD therapeutically for pain and inflammation, (studies show that CBD is a viable option for different types of chronic pain) we have also found CBD commonly utilized in the following conditions and scenarios:


  1. Anxiety, as well as insomnia. The unique thing with CBD as compared to common pharmaceutical sleep approaches is this: CBD not only helps with getting you to fall asleep, but it also helps you STAY asleep.

  2. Neuroprotection. (again, likely an anti-inflammatory component)

  3. Skin health.

  4. Cancer treatment? At this point, research is incredibly preliminary; and we wouldn’t suggest CBD as a primary treatment at this time.


Cannabinol (CBN) was actually the first cannabinoid to be identified by scientists. (Even though THC and CBD tend to get all the ‘buzz’ these days.) Despite this ‘fun fact’, there is still very little research on CBN. Thus far, this is what we understand:

1) CBN seems to be a potentially powerful sedative. I’d love to see more research on this; especially with how common sleep issues are and how pharmaceutical sleep medications lead to dependence and sometimes odd behavior.

2) CBN seems to exhibit pain-relieving effects, due to its influence over the activity of neurons. **CBN likely influences the same neurons that Capsaicin from chili peppers influences.

3) Potential as an antibiotic?? There was a study in 2008 that found CBN effective in treating MRSA. MRSA is commonly thought of as an “antibiotic resistant staph infection. [Broken record: more studies are needed.]

4) CBN certainly has anti-inflammatory capacity. CBN is being looked at as a potentially therapeutic agent for treating inflammatory diseases.

5) There are potentially other effects such as; glaucoma therapy, new bone production, epilepsy treatment, or appetite stimulant. More research is happening, and this is exciting as it relates to the natural medicine world!



Functional Medicine is rooted in daily lifestyle change that builds a healthy foundation. This foundation of good nutrition, an active mind & body, and proper sleep & recovery allows us to face challenges that inevitably come up in our modern world. Be it a virus, a stressor, or a physical challenge: we can weather it with minimal impact.




The time to build and solidify that foundation is now. (And you aren't meant to do it alone). We look at your unique biology (through functional lab testing) and support your habits (through nutritional guidance, mindfulness training, and physical medicine) to help you achieve a resilient state.


Maybe you need to step up one area of your life--> Book an online appointment!


We've all got the time to face it. Need more direction? Reach out! We'll get you on the right path.



Cabral GA, Griffin-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. 2009;11:e3. Published 2009 Jan 20. doi:10.1017/S1462399409000957

Hu SS, Mackie K. Distribution of the Endocannabinoid System in the Central Nervous System. Handb Exp Pharmacol. 2015;231:59–93. doi:10.1007/978-3-319-20825-1_3

Lee Y, Jo J, Chung HY, Pothoulakis C, Im E. Endocannabinoids in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2016;311(4):G655–G666. doi:10.1152/ajpgi.00294.2015

Di Marzo V, Piscitelli F. Gut feelings about the endocannabinoid system. Neurogastroenterol Motil. 2011;23(5):391–398. doi:10.1111/j.1365-2982.2011.01689.x

Maccarrone M, Maldonado R, Casas M, Henze T, Centonze D. Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?. Expert Rev Clin Pharmacol. 2017;10(4):443–455. doi:10.1080/17512433.2017.1292849

Nguyen BM, Kim D, Bricker S, et al. Effect of marijuana use on outcomes in traumatic brain injury. Am Surg. 2014;80(10):979–983.

McAllister SD, Glass M. CB(1) and CB(2) receptor-mediated signalling: a focus on endocannabinoids. Prostaglandins Leukot Essent Fatty Acids. 2002;66(2-3):161–171. doi:10.1054/plef.2001.0344

Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction. 1996;91(11):1585–1614.

Abrams DI. Integrating cannabis into clinical cancer care. Curr Oncol. 2016;23(2):S8–S14. doi:10.3747/co.23.3099

Pertwee RG, Howlett AC, Abood ME, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. 2010;62(4):588–631. doi:10.1124/pr.110.003004

Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–1949. doi:10.1126/science.1470919


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