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Article 25  The Endocannabinoid System and the Immune System

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Immunology (The Journal Of Cells, Molecules, Systems, And Technologies) reports nearly every cell in the immune system secretes endocannabinoids. Growing bodies of evidence support the understanding of the ECS (endocannabinoid system) playing a vital role in the immune system. Research is showing endocannabinoids help modulate various cannabinoid receptors located on several immune system cells. With high levels of cannabinoid receptors in the immune system, research reveals cannabinoids may regulate inflammation, autoimmunity, antitumor, and antipathogenic responses. Not only does the endocannabinoid system regulate these immune system responses, but several other physiological mechanisms and potentially more.


Activating immune system cannabinoid receptors triggers a series of events with the resulting function of regulating the production and migration of cytokines. Cytokines are a broad category of immune cells involved in certain signaling functions acting as agents for modulating (stimulating or suppressing) the immune system. In essence, cytokines help the immune system regulate the response of the immune system working together, alone, or against each other.


What and Where is the Immune System?


In his medical school textbook on immunology, Ivan Roitt begins describing the immune system as a handful of organs that control the creation of lymphocytes (defense cells). Organs of the immune system include adenoids, antibodies, bone marrow, lymph nodes & vessels, the spleen, thymus, tonsils, white blood cells, and more. Each piece of the immune system contributes to the overall goal of protecting and monitoring the body from a foreign organism invasion.


How Does the Immune System Function?


The immune system is primarily responsible for protecting the body from disease while also constantly monitoring the integrity of other tissue. Diseases can occur via several potential routes including bacteria, parasites, viruses, fungi, nutrient deficiencies, and potentially more. These foreign organisms are microscopic creatures capable of invading healthy tissue and using the body to survive and propagate.


Each foreign organism the immune system confronts–gets recorded–in the immune system’s memory. The immune system’s memory is known as the adaptive immune system. Whereas the other part of the immune system is known as the innate or general immune system. The innate immune system has the ability to recognize the basic patterns of infectious disease and once it recognizes a threat, the threat is eliminated. Memory cells of the adaptive immune system help the immune system respond faster to foreign organisms the body has already previously defeated.


What Role Does the Endocannabinoid System Play in the Immune System?


Several medical journal publications are publishing ongoing research involving the immune system and the endocannabinoid system. Frontiers In Immunology (one & two), Cannabis & Cannabinoid Research, British Society For Immunology, Mediators Of Inflammation, and EBIOMedicine are just a few medical journals publishing recent endocannabinoid and immune system research.


Frontiers In Immunology (a peer-reviewed medical journal focusing on the immune system) describes some basic complexities of the ECS and shows how it is expressed in both parts of the immune system. The research is showing that both the innate and adaptive immune systems are deeply influenced by endocannabinoids and phytocannabinoids. 


Other research verifies the high concentration of CB2 receptors expressed on immune cells. If an injury or illness were to occur, evidence shows the concentration of endocannabinoids increases. Endocannabinoid concentration increases due to systemic inflammation, as with sepsis or after an injury to the CNS (central nervous system).


Both plant- and endogenously-created cannabinoids influence functions of the immune system through regulating various responses. The ECS regulates the immune system’s response to cannabinoids for inflammation, autoimmune responses, and other situations requiring the help of the immune system. 


Ongoing research continues to aim at exploring complex cannabinoid signaling in diseases with inflammation, organ transplant, and other immune system effects. Research is learning that the ECS is generally recognized as the gate-keeper of homeostasis in the immune system. This gate-keeping function of the ECS positions itself as a type of orchestrator or regulator of both innate and adaptive responses of the immune system. The orchestration and homeostatic gate-keeping is shown to prevent the starting formation of disease. 


As science continues researching cannabinoids and the immune system, some testing shows how individual cannabinoids result in a phenomenon in specific cells and tissue types. In one account, the endocannabinoid 2-AG resulted in the phenomenon of direct and immune-mediated neuroprotection. Another event revealed the phytocannabinoid THC treatment–via CB1 receptors–helps prevent the killing of immune cells. 


Other phenomena associated with THC testing involves reducing intestinal tissue injury, slower collection of disability, enhancement of HIV antigen-specific immune response, and more. Several CBD phenomena were shown to improve GVHD (graft versus host disease) prevention, and more.


Evidence shows the levels of endocannabinoids increase in systemic inflammation including sepsis or after an injury to the CNS (central nervous system). Sepsis is caused by an infection that causes the organs to dysfunction because of dysregulation. This initial infection gets amplified and releases excessive amounts of pro-inflammatory and anti-inflammatory mediators. The result of the body releasing both pro and anti-inflammatory mediators triggers multi-organ failure and could lead to death. Recent research continues showing how the ECS can help in various immune treatments through proper modulation of pro and anti-inflammatory functions. 


Autoimmune Disease and the Endocannabinoid System


Environmental Health Perspectives (a peer-reviewed journal) defines that an autoimmune disease is when the body’s own immune system attacks itself. Autoimmune disease results from either an infection, genetic issue, or environmental factors.


The ECS plays an important part in autoimmune disease. Certain genetic mutations (missense) of the enzyme that synthesizes certain endocannabinoids are shown to increase the risk of various autoimmune diseases. Autoimmune diseases affected by this genetic mutation include T1DM (type 1 diabetes mellitus), RA (rheumatoid arthritis), systemic lupus erythematosus, juvenile idiopathic arthritis, graves disease, generalized vitiligo, granulomatosis with polyangiitis, and myasthenia gravis. Other more common genetic variations of the CB2 are associated with a higher risk of celiac disease and immune thrombocytopenia.


Most of the findings in medical journals are quite recent and will require more research to verify with authority. Ongoing research will continue uncovering more questions popping up about specific mechanisms on the ECS playing a central role in the orchestration of the immune system.





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