CBD: The Endocannabinoid System and Other Mechanisms

Have you ever wondered how cannabis exhibits so many different effects on our bodies?

Why does this one plant affect us in so many different ways? Well, it interacts with us primarily through the endocannabinoid system; a network of enzymes, receptor sites, and endocannabinoids that all of us have in our body.  It plays a role in things like:

  • sleep

  • appetite

  • mood

  • immune function

  • pleasure & reward

  • pain

  • memory

  • temperature regulation.

In this post, we will provide a brief overview of the endocannabinoid system, but also explain the biological mechanisms of how CBD, one of the most prevalent cannabinoids in cannabis, achieves its therapeutic effects.

Appetite & Food Intake

The endocannabinoid system plays a significant part in helping our bodies maintain homeostasis, or equilibrium. One example of this is in the regulation of appetite and food intake (this explains the munchies, lol). Interestingly, the endocannabinoid system not only regulates our appetite ("wanting" food), but also our evaluation of the food we eat ("liking" food). This, in a nutshell, explains why everything tastes so darn good when under the influence of cannabis. 

How does it work?

Our endocannabinoid system "receives" cannabinoids through its CB1 and CB2 receptors. CB1 receptors, which are most prevalent in our central nervous system, play a role in stress & anxiety management, appetite, nausea, and immune system balance. CB2 receptors, which are primarily found in our immune system, play a role in fighting inflammation and tissue damage.

Basically, cannabinoids fit like a key into these CB1 and CB2 receptors. In turn, this tells our body when to start and stop different processes. This means that any type of cannabinoid—ones made by our own body like anandamide, ones from cannabis like THC and CBD, and even synthetic cannabinoids—can "fit" into these receptors. In cannabis, the two most common cannabinoids (referred to as phytocannabinoids) are THC and CBD. Two terms to be aware of are agonist and antagonist

  • An agonist is a chemical that "activates" a certain receptor.

  • An antagonist is a chemical that "blocks" or deactivates a certain receptor.


Cannabidiol (CBD)

Contrary to popular belief, CBD has a relatively low affinity for the endocannabinoid system. Meaning, CBD is not a "first choice" for our CB1 and CB2 receptors. Instead, they would prefer to bind with endogenous anandamide (a cannabinoid produced by our own body) or THC.  You may have heard that CBD can reduce some of the psychoactive effects of THC. This is achieved through CBD's interaction with our CB1 receptors. Basically, CBD changes the way THC works on our CB1 receptors. As for our CB2 receptors (remember, these receptors play a role in inflammation), CBD & THC have inverse effects. THC activates CB2 receptors and thus triggers inflammation, while CBD does the opposite and reduces inflammation.

As stated above, CBD has a rather low affinity to our endocannabinoid system. Thus, the anti-inflammatory effects through this specific mechanism of binding to CB2 receptors is marginal. Seems confusing, huh? CBD indirectly acts on CB1 receptors to modulate the effects of THC and just barely affects our CB2 receptors. So, where do all of these benefits come from? In fact, the vast majority of CBD effects are due to its indirect activity on the endocannabinoid system and its ability to influence many other systems. The scientific literature has identified more than 65 molecular targets of CBD. Here are a few...
 

Serotonin 
At high doses, CBD directly activates one of our serotonin receptors, thereby yielding anti-anxiety effects. 
 

Ion Channels
CBD has been shown to bind with certain ion channels (specifically TRPV1) that are known to mediate pain perception, inflammation, and body temperature. Other chemicals that bind to these same receptors are eugenol—an essential oil from vanilla beans that has been shown to reduce headaches—and capsaicin—the pungent chemical in hot chili peppers. Our own cannabinoids (andandamide, remember?) also bind to these TRPV1 receptors. 
 

GPR55 Receptor
This receptor, when activated, promotes cancer cell proliferation. It is expressed in many different types of cancer. CBD works on this receptor as an antagonist (it blocks this receptor).
 

PPAR Receptor
PPAR activation has been linked to the degradation of amyloid-beta plague (the bad stuff in your brain that gives you Alzheimer's disease). CBD activates these receptors and is currently being researched for its use as an Alzheimer treatment.
 

Anandamide Reuptake Inhibitor
CBD has a neuroprotective effect against seizures by increasing the amount of our own endocannabinoids in the brain's synapses. It does this by inhibiting the reuptake and breakdown of anandamide (the endocannabinoid made by our body).
 

Adenosine Reuptake Inhibitor
In a similar way to its effects on anandamide, CBD boosts the levels of adenosine in our brain. This regulates adenosine receptor activity, which have broad anti-inflammatory and anti-anxiety effects on our body. 

Forrest BloomComment