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The effects of CBD to your body
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I touched briefly on how the endocannabinoid signalling system works in a previous blog, and I sincerely hope you’ve all been doing your homework because this one is going to be based reasonably heavily on the content of that. Over the course of this post we will be covering several topics, so there may be some bouncing around. Specifically I want to look at how CBD and THC exhibit their effects in regards to how they bind to their respective receptors, and then how this transfers to other signalling systems. Like the last blog on this topic, it’s probably going to be quite a dense read. Good luck!
I touched briefly on how the endocannabinoid signalling system works in a previous blog, and I sincerely hope you’ve all been doing your homework because this one is going to be based reasonably heavily on the content of that. Over the course of this post we will be covering several topics, so there may be some bouncing around. Specifically I want to look at how CBD and THC exhibit their effects in regards to how they bind to their respective receptors, and then how this transfers to other signalling systems. Like the last blog on this topic, it’s probably going to be quite a dense read. Good luck!
Despite the recent explosion in interest towards CBD, there has been a surprising level of knowledge about it for some time. In-depth research has been carried out since as early as the 1940s, where the structure of the molecule and how it affects the chemical function was determined (Pertwee, 2006). In conjunction with the increasing knowledge of the newly discovered endocannabinoid system (ECS), experiments investigating the pharmacology of the various cannabinoids followed soon after. There are two ECS receptors that the various phytocannabinoids can bind to, referred to as CB1 and CB2. CB1 receptors are found predominantly in the central nervous system, whereas the CB2 receptors are mostly located on immune cells. This spread of where the cannabinoids can have an effect is the reason for CBD’s wide range of potential application.
The reason that CBD has such different effects when compared to the other main cannabinoid – THC – is due to how they bind differently to the two cannabinoid receptors. A molecule that binds to a receptor protein and elicits a response from the cell is referred to as an agonist, whereas a molecule that inhibits a response is called an antagonist. To start with something nice and simple, THC is a CB1 and CB2 receptor partial agonist; it binds with the receptors, but not as effectively as a molecule specifically designed to bind there. For example, Anandamide (which we talked about in the previous ECS blog) is produced by the body specifically to bind with CB receptors and therefore will display higher efficiency at binding with them than THC will. As agonists, these molecules induce a response, explaining their effects.
From this explanation of how different types of molecule binding affect the responses induced by them and the information that THC is an agonist, we could reasonably assume that CBD is the opposite of THC and is an antagonist. Unfortunately it isn’t this simple. CBD has very low binding potential for both CB receptors and is actually an antagonist of other receptor antagonists. The easiest way to think of this is as if the body’s response is a bar graph. When an agonist binds to a receptor, it increases the height of the bar because it is inducing a greater response. CBD however will prevent this agonist response from occurring by antagonising the molecule that is binding, thus lowering the bar back closer to its original starting point. We can see this in how CBD acts on the body, typically reducing overexpression of things like anxiety, pain or inflammation. Sometimes CBD’s effects don’t involve it binding to a receptor at all!
From this explanation of how different types of molecule binding affect the responses induced by them and the information that THC is an agonist, we could reasonably assume that CBD is the opposite of THC and is an antagonist. Unfortunately it isn’t this simple. CBD has very low binding potential for both CB receptors and is actually an antagonist of other receptor antagonists. The easiest way to think of this is as if the body’s response is a bar graph. When an agonist binds to a receptor, it increases the height of the bar because it is inducing a greater response. CBD however will prevent this agonist response from occurring by antagonising the molecule that is binding, thus lowering the bar back closer to its original starting point. We can see this in how CBD acts on the body, typically reducing overexpression of things like anxiety, pain or inflammation. Sometimes CBD’s effects don’t involve it binding to a receptor at all!
The final thing I’d like to discuss is the lack of specificity of CBD. Obviously a great number of its effects are because it acts on the ECS, which makes sense as it is a cannabinoid itself. However, there is also evidence that CBD can have effects on other signalling system within the human body. One such example is on the serotonergic system, which is best known for its contributions to feelings of happiness. The full range of effects the serotonin signalling system is involved in is vast though, including things like cognition, memory and many physiological processes. To make things even more complicated, Russo et al. (2005) found that when it affects the serotonergic system, CBD actually acts as an agonist for the 5HT1A receptors that make up part of the system.
Once again, if you managed to make it this far – congratulations! Cell signalling is a complicated topic with lots of mechanisms and terminology to understand. The phytocannabinoids make the situation even more difficult because they act differently depending on which signalling system they affect. Hopefully you at least have an understanding of how this binding works both in the ECS and other systems and how the binding of these molecules determines their effects.
Once again, if you managed to make it this far – congratulations! Cell signalling is a complicated topic with lots of mechanisms and terminology to understand. The phytocannabinoids make the situation even more difficult because they act differently depending on which signalling system they affect. Hopefully you at least have an understanding of how this binding works both in the ECS and other systems and how the binding of these molecules determines their effects.
Refs:
Pertwee (2006) – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760722/
Russo et al. (2005) – https://link.springer.com/article/10.1007%2Fs11064-005-6978-1
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