Could CB1 Receptor Displacement Cause Neurodegeneration?
As research escalates and we get to know more about cannabis medicine, most people are aware now that we have an endocannabinoid system and that the phytocannabinoids in the cannabis plant interact with one another. We know that we have CB1 and CB2 receptors and that CB1 receptors are mostly found in the brain. We also understand that neurodegenerative disorders mostly come from distortions in the brain.
Neurodegenerative disorders cause a significant social and economic burden. To effectively treat these types of disorders, is quite problematic for neuroscientists and neurologists. The endocannabinoid system with its endocannabinoids has a neuro-signaling system where endogenous and exogenous components interact. Cannabinoids from the cannabis plant show promising neuroprotective activity due to their anti-oxidative, anti-excitotoxic, and anti-inflammatory properties.
The CB1 receptors in the brain are where the phytocannabinoids bind. The CB1 receptor is one of the most abundant G-protein coupled receptors in the central nervous system. This receptor is associated with many neurodegenerative disorders. CB1 receptors must be placed in the exact spot in the brain to be 100% effective. So, what happens if there is some sort of misplacement? It could result in nerve transmission problems and things like pain, mood and memory could be affected.
Understanding Nerve Cell Communication
By estimation, the brain has about 100 billion neurons. These neurons are constantly in communication with one another. A nerve cell contains a cell body, an axon, certain dendrites. The dendrites and the axon are responsible for communication from one nerve cell to another. Then there are also contact points, called the synapses. When a message is sent, a neuron releases a neurotransmitter (chemical) from the axon terminals to the synapses. The neurotransmitter moves over the synapse to bind to a receptor protein on the dendrites of another neuron. This is how the message is passed along.
How the CB1 Receptor works in Nerve Cell Communication
CB1 receptors are involved with the flow of information at the synapses. They bind to neurotransmitters called endocannabinoids. The endocannabinoids are always amongst neurotransmitters with a contradictive action. Instead of sending the message from axons to dendrites, they send them in the opposite direction. The dendrites now release the endocannabinoids, which then bind to the CB1 receptors on the axon terminals. This has a backward effect, called retrograde signaling. It dampens the release of other neurotransmitters and slows down brain activity. THC has this effect on the brain.
Researchers are trying to understand the polarity on the surface of the axon, and how it affects the CB1 receptor. When a structure has two opposite ends, it works like magnets. CB1 receptors have an exceedingly high polarized axonal surface with the purpose to weaken neurotransmitter release and modulate synaptic plasticity (the ability of the brain to adapt and change to new information). There are two mechanisms involved in this process:
Selective delivery of the newly made CB1 receptor to the axon. It also prevents delivery to the dendrites
Keeping presence in axons and retrieval from dendrites
CB1 Receptors Must be on the Exact Spot on Nerve Cells in the Brain
The CB1 receptors have to be taken to the place where it needs to be. Here, a specific component, C-terminal motif Helix 9 (H9), has a particularly important role to play. When there is a deficiency of H9, mistakes occur in the delivery of CB1 receptors to the axon. This leads to a reduced ability of the axons and dendrites to keep the CB1 receptors in the correct place. As a result, it has a significant negative impact on the pathology of neurodegenerative diseases.
A cell builds its own CB1 receptors, much like other proteins. The balance of having sufficient H9 components are vital to the correct placing of CB1 receptors. The receptors go directly to the axon before it moves on to axon terminals. A specific region of the CB1 receptor is important for sending the receptors to the axon. The exact spot is necessary so that receptors do not go to the dendrites instead. This specific spot created by the H9 compounds allows the receptors to stay on the axon surface and allows them to be available for binding with the endocannabinoids.
What does this mean for Cannabis Medicine?
The CB1 receptors play an important role in the response from the cannabinoids found in the cannabis plant to the endocannabinoid system. When they are activated, many diseases and conditions benefit from the therapeutic properties it has. This includes conditions like chronic pain, epilepsy, and multiple sclerosis, to name a few. The CB1 receptors have become especially important to understand as a clinical target. To understand the complexity of the cell biology and trafficking behavior of this receptor is of utmost importance. The more research is done, the more clarity of the complex behavior is revealed. Here we have learned that H9, as a regulator, is important in moving CB1 receptors to the exact spot where it needs to be. We have also learned that if H9 is depleted, it holds significant influence in neurodegenerative development.
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