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The two most common types of cannabinoids found in the human body, however, are anandamide and 2-arachidonoylglycerol, otherwise known as 2-AG. As previously mentioned, cannabinoids are the “keys” of the endocannabinoid system. Research is still underway in regards to our cannabinoid receptors, and many scientists believe in the existence of an as yet unproven CB3 receptor.

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Heat shock protein 60 was the first candidate DAMP reported to induce TLR4 activation . Within months, necrotic cells were shown to induce proinflammatory gene expression and dendritic cell maturation via TLR2 . Since then, several DAMPs have been identified, and some are intracellular molecules to which innate immune cells are not normally exposed. Analogous to PAMPs, cell surface and intracellular TLRs recognize different types of DAMPs, although endogenous ligands have not been identified for all TLRs .

CB2 Receptors are found all around the body but are most prominent in areas related to the immune system. Considering humankind has a long term relationship with both hemp and cannabis, it may come as a surprise that the endocannabinoid system is a relatively recent discovery. With hemp/CBD oil growing rapidly in popularity, the endocannabinoid system is becoming more and more a common part of CBD oil popular discussion. Due to its widespread effects in the human body, the endocannabinoid system shows a promising future in treating many diseases and conditions. When these receptors are activated, they help to reduce inflammation which is believed to play a role in many diseases and conditions.

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  • Parts of the body with the highest concentrations of these receptors are the areas that are most affected by cannabinoids.
  • Endocannabinoid receptors are located in different parts of the body, scattered in varying concentrations.
  • CB2 receptors are highly concentrated in the spleen, tonsils, thymus, and immune cells, with a small amount existing in the brain.
  • Activating CB2 receptors can help destroy the main component of the plaque that is found in the brains of those with Alzheimer’s disease.

When it is underactive, our protection from disease is down and we typically become ill. The way this actually works in practice is, the neurons of our brain release neurotransmitters.

This allows the ECS to provide the same fine-tuned balancing act it does for the CNS. If our immune system is overactive, it can attack the body’s own cells causing serious health issues.

These neurotransmitters come out of the presynaptic cell and jump a small distance across to the postsynaptic cells, after which they bind to receptors. This binding is one node or step of the brain cell network, with a large trail of receptors helping to deliver the message or signal across the brain. It is known that it does not bind with the CB1 and CB2 receptors in the same way as THC. However, the way it does interact with the endocannabinoid system is still the subject of a lot of speculation and research.

Matzinger proposed that the immune system does not distinguish between self and non-self-antigens per se but rather is designed to detect danger . The apparent paradox of sterile inflammation is resolved by realization that pattern-recognition receptors, including TLRs, recognize endogenous ligands. The endogenous molecules called damage-associated molecular patterns are created or released upon tissue injury or cell death .

Evidence is growing that endocannabinoid levels change during various disease processes due to altered catalytic activities of the biosynthetic or metabolizing enzymes. In several animal disease models, modified endocannabinoid levels exert pro- or anti-inflammatory effects on innate immune cells based on enzyme inhibitors, transporter inhibitors, and mice genetically deficient in the enzymes. For many years, one puzzling aspect of innate immunity has been inflammatory responses in the absence of an infection that contribute to tissue damage during autoimmune diseases and chronic inflammatory diseases.

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