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The Endocannabinoid System

Human beings have been using cannabis for its medicinal and psychoactive properties for thousands of years, but there’s always been a veil over information regarding how and why cannabis works so well with treating such a wide variety of medical conditions. For example, cannabis has been known for decades to be very helpful in the treatment of glaucoma due to it’s ability to lower the intraocular pressure of the eye, or in other words lower the fluid pressure to prevent optic nerve damage. But how does it work?

Endocannabinoids

Endogenous cannabinoids are a family of bioactive lipids that interact with and activate Endocannabinoid receptors via neural transmission. Naturally formed cannabinoids can be found sparsely in the brain and in other tissues throughout the body, and are tasked with homeopathic regulation of functions such as pain perception, memory, mood, and appetite. One event that triggers the natural production of cannabinoids in your body is Noxious Stimulus, a potentially or actually tissue damaging event. Your body is alerted of this event and in response, synthesizes it’s own cannabinoids on demand and releases them to activate presynaptic cannabinoid receptors in specific areas.

Endocannabinoid Receptors

Decades after the discovery of Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient in cannabis which was first isolated in 1964 by Raphael Mechoulam and Yechiel Gaoni, the identification and successful cloning of the first cannabinoid receptor (CB1) came, and shortly after, cannabinoid receptor 2 (CB2).

  • Cannabinoid receptor type 1 (CB1) receptors are thought to be one of the most widely expressed Gαi protein-coupled receptors in the brain. CB1 receptors have shown particularly high levels of expression in cortex, basal ganglia, hippocampus, cerebellum, and low levels of expression in brainstem nuclei. Also found in medulla oblongata and spinal cord.
  • CB2 receptors are mainly expressed on T cells of the immune system, on macrophages and B cells, and in hematopoietic cells. They also have a function in keratinocytes and are also expressed on peripheral nerve terminals. These receptors play a role in antinociception, or the relief of pain. Activation of peripheral CB2 receptors generates an antinociceptive response in situations of inflammatory hyperalgesia and neuropathic pain.

 

Interaction between Cannabinoids and Receptors

Cannabinoid receptors are Gi/o-protein coupled receptors anchored in the cell membrane, and can be found throughout most of the body’s systems. So how do Cannabinoids interact with their host receptors? Here’s an example below.

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The major inhibitory neurotransmitter in the central nervous system is gamma-aminobutyric acid (GABA). Above, you can see a representation of a GABA neurotransmitter synapsis (the junction point between two neurons communicating), containing CB1 receptors to show potential targets for therapeutic intervention. Endocannabinoids are synthesized in membranes of neurons and other nervous cells and released to the in-between synaptic space to activate presynaptic CB1 receptors. Enhancement of cannabinoid receptors activity can be obtained by different pharmacological manipulations as, for example, administering cannabinoid receptor agonists or inhibiting either the reuptake or the degradation of the endocannabinoids.

In summary, cannabinoids have the ability to alter communication from one neuron to another and they hold a lot of undiscovered medicinal potential. Further study of the various cannabinoids and their receptors could lead to breakthroughs in pain management, neuroprotection and control of motor function aiding in conditions like Parkinson’s Disease, treatment of spinal injury, weight control, conditions like anxiety, neuropathy, glaucoma, nausea, emesis, wasting diseases. Promising data has already been collected in treatment with inflammatory control, cancer, epilepsy, PTSD, depression, gastrointestinal disease, traumatic brain injury and stroke. The list goes on and on.

Cannabis has an exciting future ahead of it, and the science behind it is finally becoming unveiled!

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