Recently, CBD has been touted as a miracle drug for pain. But how does it really work? 

Dr. Min here with Buzzn 👋🏼. I’m going to explain the science behind how CBD may work with your body. But, it’s about to get SUPER technical as we delve into the science of it all. 

Ready? Let’s start with the basics.


Cannabinoids are small molecule neurotransmitters. Some are synthesized in the body called endocannabinoids (endo = internal) and others are taken or administered exogenously (exo = external). 

Cannabinoids serve to do 2 major things:

  1. Regulate neuron function
  2. Play some roles in reducing inflammation

The first class of cannabinoids are those that are made naturally via biosynthetic pathways (the biological sequence of combining the production of an end-product, in this case endogenous cannabinoids) by your own cells. These are called endocannabinoids. The 2 major endocannabinoids are:

  1. 2-AG (2-Arachidonoylglycerol)*
  2. AEA (anandamide)* 

*both are derived from arachodonic acid  (the essential fatty acid that plays a key role in cellular signaling) 

Exocannabinoids (or Phytocannabinoids)

The second class of cannabinoids are those that are taken exogenously (externally), called Exocannabinoids or commonly referred to as Phytocannabinoids. These are the cannabinoids from whole plant hemp extracts like broad or full-spectrum CBD products.

Pain signals

To understand how we feel pain, I want to explain how pain is perceived by the brain: 

Perception of pain via central nervous system:

When you experience pain, your brain signals an action potential to go down the axon of the presynaptic neuron causing Ca+ (Calcium) influx into the cell from extracellular fluid to intracellular fluid, ultimately depolarizing the neuron.

Ok, we get that was a mouthful. But to put it into simpler terms, pain is essentially perception. It’s created by our brain and is widely interconnected throughout our body. There are changes that happen in our brain as we experience pain. We have presynaptic neurons & post synaptic neurons that signal back and forth to each other as we experience pain. This is how our cells communicate: the pre-synapse signals an action potential to the post synapse. The pre-synaptic neuron opens its Ca (calcium) voltage-gated channels, so there is an influx of calcium going into the pre-synapse. Since Ca+ (calcium) is positively charged (remember protons in high school chemistry???), the influx of Ca+ depolarizes the presynaptic neuron. Depolarization of the presynapse is technically not a good thing because this causes glutamate neurotransmitters to be released into the synaptic cleft (I’ll explain this below).

Got it? Ok, good. Let’s move on…

Action potential (AP):

It’s a change in an electrical potential impulse along the membrane of a muscle or nerve cell.  

Glutamate release:

The perception of pain is initiated by our cells communicating. Action potentials run down the pre-synaptic neuron, which in turn triggers the opening of voltage-gated Ca+ (Calcium) channels. Due to the opened gateways, there is a huge Ca+ influx into the neuron (depolarizing the membrane of the cell), which then triggers neurotransmitter (i.e Glutamate) release into the synaptic cleft.

Glutamate is the main excitatory neurotransmitter that communicates the perception of pain and is released by the presynaptic neuron due to Ca+ influx of the membrane, aforementioned. Consequentially, the release of glutamate then binds to the receptor on the post-synaptic neuron, depolarizing it as well. Glutamate travels in a retrograde fashion across the synapse and depolarizes the membrane to initiate the pain cascade. 

Let’s put that together. So in a nutshell

Increase glutamate = Increase pain signaling = Increase pain perception

CBD for pain relief

Mechanism of Action:

How do cannabinoids come into play? – Endocannabinoids (2-AG & AEA) and Phytocannabinoids (cannabinoids derived from the plant) both have binding affinity to CB1 receptors in the post-synaptic neuron. CB1 receptor is a G-protein receptor that serves as a target for both endocannabinoids and phytocannabinoids. In the brain, CB1 receptors are located on presynaptic terminals, and, when signaled, these receptors modulate neurotransmitter release. Cannabinoids* bind to CB1 receptors and stimulate K+ (Potassium) efflux in the post-synapse and also inhibits Ca+ (Calcium) influx in the pre-synapse. K+ efflux results in hyperpolarization of the cell. Hyperpolarization prevents pain signaling by stopping the release of glutamate.

*Note: Cannabinoids have different binding affinity to CB1 receptors, and some cannabis-derived compounds bind to receptors other than CB1 and CB2, including the TRPV1 receptor and the GPR55 receptor.

Here’s the breakdown:
  1. Cannabinoids inhibit Ca+ (calcium) influx in the pre-synaptic neuron, therefore inhibits depolarization of the cell membrane.
  2. Cannabinoids stimulate K+ (Potassium) efflux in the post-synaptic neuron, therefore hyperpolarizing the cell membrane.
  3. Cannabinoids feed back on the cannabinoid receptor (CB1) and decrease release of glutamate, reducing  pain signaling to perception cascade.

In order to decrease pain, the best way to sum it up is:

Decrease glutamate = Decrease pain signaling = Decrease pain perception

As you can see, glutamate is the primary neurotransmitter associated with pain. By decreasing glutamate release, you will decrease pain signaling and ultimately lower your body’s perception to pain. Cannabinoids (whether synthesized by the body or taken exogenously) may help regulate any inflammatory imbalances to manage pain points.

The human body’s endocannabinoid system (ECS) is quite an amazing system of checks & balances to keep body and mind aligned. If we have left you wanting more or if you have any questions, we would love to help you understand it better. Please email us at and one of our healthcare professionals will get back to you!


  • Cannabinoids activate CB1 in the presynaptic terminal
  • Hyperpolarization of post-synaptic neurons via K+ efflux
  • Inhibit depolarization of pre-synaptic neurons by stopping Ca+ influx
  • Decrease Glutamate release via negative feedback
  • Decrease pain perception




Author admin

Leave a Reply

Your email address will not be published. Required fields are marked *