There is evidence that Cannabidiol (CBD) can provide pain-relief by working in the central nervous system (CNS), or in the brain and spinal cord.

Dr. Min here with Buzzn. I’ll explain one way in which CBD may work for pain relief. But, It’s about to get SUPER technical as we delve into the science behind it.

Ready? Let’s start with the cannabis 101.


Cannabinoids are fatty phospholipid molecules. Some are synthesized in the body called endocannabinoids (endo = internal) and others are taken or administered exogenously with exocannabinoids (exo = external). Exocannabinoids will be used interchangeably with phytocannabinoids (phyto = plant).

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


The first class of cannabinoids are those that are made naturally by our own cells. These are called endocannabinoids. The 2 major endocannabinoids are:

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

*Both are derived from arachidonic acid from fatty lipid precursors in the membrane and is a key role in cellular signaling.


The second class of cannabinoids are those that are taken exogenously (externally), called Exocannabinoids. These are cannabinoids from the cannabis or hemp plant. THC and CBD are the most popular phytocannabinoids. Each elicit very different therapeutic effects in the body.


To understand how we feel pain, I’ll start by explaining how pain is perceived. But first, let’s define an Action Potential, the first step in pain transmission.


It’s a change in an electrical potential impulse that travels along the membrane of a muscle or nerve cell, typically associated from an external force (ie. stubbed toe).

Now, let’s move onto how pain is perceived.


Pain is perception. It’s created by our brain and widely interconnected throughout the body. On a microscopic level, action potentials travel down the axon of the presynaptic neuron. This in turn causes Ca+ (Calcium) influx into the cell from extracellular fluid to intracellular fluid. Because Ca+ is positively charged by nature (remember protons in high school chemistry?), its influx into the presynaptic neuron depolarizes the membrane. Depolarization is not a good thing because it triggers the release of glutamate, the pain neurotransmitter.


Glutamate is the main excitatory neurotransmitter that communicates pain perception. When Glutamate binds to its receptors on the post-synaptic neuron, this activates NAPE & DAGL enzymes to synthesize anandamide and 2-AG, respectively. These endocannabinoids are made on demand and travel in a retrograde fashion from the post-synaptic neuron to the pre-synaptic neuron. The retrograde signaling is quite unusual because most neurotransmitters (like NE, DA, and 5HT) travel from the pre-synaptic neuron to the post- synaptic neuron to elicit its physiological responses.

In a nutshell:

Action Potential transmission = Glutamate release = Pain signals increase = Pain perception increases.


How does CBD come into play?   Remember the endocannabinoids (2-AG & AEA) are released from the post-synaptic neuron due to glutamate release. These cannabinoids travel back to the pre-synaptic neuron to bind to the CB1 receptors located on the terminals of the pre-synaptic neuron. Cannabinoids bind to receptor site and prevents depolarization of the neuron by stopping the Ca+ influx. Phytocannabinoids like THC work similarly to endocannabinoids. THC for example mimics an endocannabinoid at CB1 receptors. It’s a lot more complicated than this because of the different intrinsic activities of certain ligands. Ultimately, cannabinoids inhibit the neurotransmitter storm.


  • Cannabinoids inhibit Ca+ (calcium) influx in the pre-synaptic neuron. Membrane is depolarized.
  • Cannabinoids feed back on the CB1 receptor in a retrograde fashion to decrease glutamate release and therefore inhibit the excitatory neurotransmitter storm caused by an action potential.

To sum it up:

Cannabinoids decrease glutamate release. Glutamate is the neurotransmitter responsible for pain.

As you can see, by decreasing glutamate release, we can decrease pain signaling and ultimately lower our body’s perception to pain. Cannabinoids may help regulate any inflammatory imbalances in our body and work onto cannabinoid receptors in the CNS to decrease neuronal firing caused by painful stimuli.

The human body’s endocannabinoid system (ECS) is quite an amazing system of checks & balances that keep our mind & body properly functioning.   If you have any questions, please email me at




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