How CBD Works: How CBD Works With Your Body’s Endocannabinoid System

CBD is growing in popularity but how does it work?


There are approximately 113 known cannabinoids found in the hemp plant, scientists are still finding new cannabinoids today. The most prominent cannabinoids are Tetrahydrocannabinol (THC) and Cannabidiol (CBD).


A cannabinoid is a compound that interacts with our body’s Endocannabinoid System (ECS), which in short, is a network of receptors that interacts with cannabinoids to maintain vital functions throughout our body. Scientists discovered the first cannabinoid receptor in 1988, and by 1993, they had identified a second receptor. In 1995, the two receptors were classified as the CB1 and CB2 receptors.


CB1 receptors are found abundantly in regions of the brain responsible for mental and physiological processes such as memory, high cognition, emotion, and motor coordination, while CB2 receptors are found throughout the central nervous and immune systems.


It was first believed that CBD interacted with the CB1 and CB2 receptors directly. We now know that CBD has very little binding affinity for either of the two receptors. CBD works in the endocannabinoid system through multiple molecular pathways.


So far scientists have identified 65 molecular targets of CBD. CBD does indirectly work on both (CB1 and CB2) receptors, cannabidiol modulates, several non-cannabinoid receptors and ion channels by acting through various receptor independent pathways.



Reuptake of Neurotransmitters

For an example CBD will affect the reuptake of the endogenous neurotransmitters. They also inhibit or enhance certain G-protein coupled receptors by affecting the binding action.


Because THC and CBD have different molecular structures, they do not interact with the CB1 and CB2 receptors in the same manner. This greatly differentiates the effects each has on the body. THC interacts with your endocannabinoid system by directly binding to both CB1 and CB2 receptors.


Now this is where the different positions of that tiny atom come into play. When a direct bond is formed by THC the reaction creates signals that are sent to the brain, which results in the psychoactive effects of “getting high”. In stark contrast, CBD that does not directly bind to the receptors and is non-psychoactive.


CBD has also been found to even negate the bond between THC and the CB1 receptors, effectively neutralizing the psychoactive and anxiogenic effects induced by THC. While THC certainly offers tremendous benefits, its mind-altering effects aren’t preferred by everyone. CBD on the other hand, can deliver many of the same benefits of THC without inducing its psychoactive effects. 


Serotonin Receptors

Scientists have discovered that CBD in high concentrations will directly activate the 5-HT1A serotonin receptor, effectively boosting the brain’s serotonin system. Serotonin receptors are found in both the central and peripheral nervous systems.


When CBD activates the receptors there is an intracellular cascades of chemical messages that produce either an excitatory or inhibitory response. It has also been found that CBDa (also known as raw or unheated CBD), has a stronger affinity for the 5-HT1A receptor. Making CBDa a potent anti-emetic.


Vanilloid Receptors

CBD directly binds to the TRPV1 receptor also known as the vanilloid receptor. The TRPV1 receptor functions as an ion channel. When the TRPV1 is activated it is involved in the regulation of various physiological functions. It has been found that TRPV1 plays an important role in many of the body’s physiological and pathological conditions.


CBD can also act as an opposite, it can be an antagonist that blocks or deactivates certain receptors such as the GPR55. Scientists are still studying the GPR55 receptor and it is believed to be part of the cannabinoid family. They have found the receptor in the brain and that it helps regulate physiological processes. It is also known the GPR55 is a target for cannabinoid binding.


Scientist also know that it promotes osteoclast cell function and promotes cancer cell proliferation. Research is still in the early stages but CBD does appear to block the activity of GPR55 in the hippocampus.



CBD has been found to activate the PPARs (peroxisome proliferator activated receptors). When CBD activates PPARs it has an anti-proliferative effect and degrades amyloid-beta plaque. The PPAR receptors have also been found to regulate energy homeostasis, lipid uptake, insulin sensitivity, and other metabolic functions. But at this time it is unclear what role CBD plays in the regulation of these systems.


At this point you might be asking, how does CBD get inside a human cell?

After ingesting or applying CBD topically, it will first pass through the cell membrane by hitching a ride with a fatty acid binding protein (FABP). The FABP are the same transport molecules that our own endocannabinoids hatch a ride on. After FABP pass through cellular wall membrane’s they have several targets within the cell such as modulate receptors that are on the surface of a nucleus. Once attached it will regulate the gene expression and mitochondrial activity.


When adding CBD to your diet it interferes with the normal endocannabinoid passage by reducing anandamide’s access to the FABP transport molecules. This delays your normal endocannabinoid passage to the cell’s interior thereby increasing anandamide and endocannabinoid levels within the brain’s synapses. The anandamide reuptake and breakdown inhibitor of CBD is the key mechanism of neuroprotective effects and other benefits.


CBD can either enhance or inhibit how a receptor transmits a signal by changing the shape of the receptor. This function is called allosteric receptor modulator. CBD acts as a positive allosteric modulator of the GABA-A receptor. It enhances the receptor’s binding affinity for endogenous agonist and gamma-aminobutyric acid (GABA).


On the flipside CBD acts as a negative allosteric modulator on the cannabinoid CB1 receptor. The interaction changes the shape of the CB1 receptor and weakens THC’s ability to bind with the receptor which lowers THC’s psychoactive effects.


The scientific discovery of the endocannabinoid system and how receptors interact with cannabinoids has changed our understanding of the human biology. It is now fact that cannabinoids can regulate physiological system within the human body.


Cannabinoid therapy is connected to the part of the biological matrix where body and brain meet. Since CBD (cannabidiol) and other compounds in hemp are so similar to the chemicals created by our own bodies, they are integrated better than many synthetic drugs.