The endocannabinoid system / The endogenous cannabinoid system, named after the plant that led to its discovery, is perhaps the most important physiologic system involved in establishing and maintaining human health.
They are named after the cannabinoids in the hemp / cannabis plant as their chemical structure is very similar.
Endocannabinoids are cannabinoids that are produced by our body and are able to activate the cell membrane cannabinoid receptors. Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells.
Endocannabinoids serve as intercellular lipid messengers, and they are signaling molecules released from one cell membrane to activate the cannabinoid receptors on other nearby cell membranes.
Their signals are retrograde which means that they move in the direction opposite to the conventional direction of the intercellular movement of signals, the exchange of substances and communication.
This is precisely why they act as active substances – they reduce the secretion of insulin into the blood, alleviate pain and calm the immune system among other benefits.
Endocannabinoids and cannabinoids are also found at the intersection of the body’s various systems, allowing communication and coordination between different cell types.
At the site of an injury, for example, cannabinoids can be found decreasing the release of activators and sensitizers from the injured tissue, stabilizing the nerve cell to prevent excessive firing, and calming nearby immune cells to prevent release of pro-inflammatory substances.
Three different mechanisms of action on three different cell types for a single purpose: minimize the pain and damage caused by the injury.
The human body naturally produces 6 different Endocannabinoids:
1. Arachidonoylethanolamine (anandamide or AEA) – The name anandamide derives from an ancient Sanskrit word, meaning bliss.
Anandamide acts as a chemical messenger between the embryo and uterus during implantation of the embryo in the uterine wall. Therefore, it is one of the first means of communication between mother and child.
Pharmacologically, AEA is similar to THC although their chemical composition is different. Anandamide binds to CB1 receptors and, to a lesser extent, to CB2 receptors.
Anandamide is found in almost all animal tissue and in some plants.
2. 2-Arachidonoylglycerol (2-AG) – 2-AG is a cannabinoid that binds to and acts as an antagonist, meaning that it decreases the effect of the neurotransmitters.
It mostly works in the brain but has also been found in maternal and bovine milk, since it stimulates appetite and thus helps with the development of the newborn.
Pathophysiological processes, such as myocardial infarction, ischemia or neuronal damage, cause a significant increase in the concentrations of AEA and 2-AG in the organism.
3. 2-Arachidonyl glyceryl ether (noladin ether) – Noladin ether mainly binds to CB1 receptors; it binds poorly to CB2 receptors.
Noladin ether signals food consumption and body weight through CB1 receptors. Therefore, it has an impact on metabolism efficiency, appetite level and body weight.
4. N-Arachidonoyl dopamine (NADA) – NADA mainly binds to CB1 and TRPV1 (vanilloid) receptors. NADA is a vasodilator, meaning that it widens blood vessels and thus decreases blood pressure.
It is also a potent inhibitor reducing the spread of breast carcinoma and alleviating pain.
5. Virodhamine (OAE) – OAE acts as a CB2 antagonist and partially acts as a CB1 antagonist. Virodhamine is capable of lowering body temperature.
6. Lysophosphatidylinositol (LPI) – LPI, just like CBD, binds to GPR55 cannabinoid receptors.
In the brain, LPI acts as a vasodilator – it widens blood vessels and releases calcium ions into arterial endothelial cells (interior surface of blood vessels).
The endocannabinoid system, with its complex actions in our immune system, nervous system, and all of the body’s organs, is literally a bridge between body and mind.
By understanding this system we begin to see a mechanism that explains how states of consciousness can promote health or disease.
In addition to regulating our internal and cellular homeostasis, cannabinoids influence a person’s relationship with the external environment. Socially, the administration of cannabinoids clearly alters human behavior, often promoting sharing, humor, and creativity.
What Are Cannabinoid Receptors?
While it may seem we know a lot about cannabinoids, the estimated twenty thousand scientific articles have just begun to shed light on the subject.
Large gaps likely exist in our current understanding, and the complexity of interactions between various cannabinoids, cell types, systems and individual organisms challenges scientists to think about physiology and health in new ways. The following brief overview summarizes what we do know.
Cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system. When cannabinoid receptors are stimulated, a variety of physiologic processes ensue.
Researchers have identified two cannabinoid receptors: CB1, predominantly present in the nervous system, connective tissues, gonads, glands, and organs; and CB2, predominantly found in the immune system and its associated structures.
Many tissues contain both CB1 and CB2 receptors, each linked to a different action.
Endocannabinoids are the substances our bodies naturally make to stimulate these receptors. The two most well understood of these molecules are called anandamide and 2-arachidonoylglycerol (2-AG).
They are synthesized on-demand from cell membrane arachidonic acid derivatives, have a local effect and short half-life before being degraded by the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Phytocannabinoids are plant substances that stimulate cannabinoid receptors.
Delta-9-tetrahydrocannabinol, or THC, is the most psychoactive and certainly the most famous of these substances, but other cannabinoids such as cannabidiol (CBD) and cannabinol (CBN) are gaining the interest of researchers due to a variety of healing properties.
Most phytocannabinoids have been isolated from cannabis sativa, but other medical herbs, such as echinacea purpura, have been found to contain non-psychoactive cannabinoids as well.
Interestingly, the cannabis plant also uses THC and other cannabinoids to promote its own health and prevent disease.
Cannabinoids have antioxidant properties that protect the leaves and flowering structures from ultraviolet radiation – cannabinoids neutralize the harmful free radicals generated by UV rays, protecting the cells.
In humans, free radicals cause aging, cancer, and impaired healing. Antioxidants found in plants have long been promoted as natural supplements to prevent free radical harm.
As we continue to sort through the emerging science of cannabis and cannabinoids, one thing remains clear: a functional cannabinoid system is essential for health.
So far, 4 receptors have been investigated, They are located in the cell membranes in the central nervous system and peripheral tissues.
CB1 cannabinoid receptors – CB1 receptors are found in all vertebrates; mammals, birds, fish and reptiles, and they have existed for more than 500 million years.
CB1 receptors are mainly present in the central nervous system and to a lesser extent in peripheral tissues.
They are found in numerous regions of the brain: motor control (basal ganglia and the cerebellum), memory and cognitive functions (cortex and hippocampus), emotions (amygdala), sensory perception (thalamus) and autonomic and endocrine functions (hypothalamus, pons and medulla). In the body they can be found in the testicles, ovaries, uterus, vascular endothelium, spleen and peripheral nerves.
CB2 cannabinoid receptors – CB2 receptors are mainly located in the peripheral nervous system, spleen, tonsils and lymph nodes.
They are also present in the motor control region of the brain (basal ganglia and the cerebellum). CB2 receptors are primarily responsible for anti-inflammatory and autoimmune therapeutic effects.
GPR55 cannabinoid receptors – GPR55 receptors are most commonly found in the brain and more specifically in the cerebellum which is important for motor control. GPR55 receptors located on bone cells regulate the growth of bone cells.
GPR55 receptors are activated by Δ9-THC plant cannabinoids and the endocannabinoids anandamide, 2-AG and noladin ether to lesser extent.
WHAT IS CANNABIDIOL (CBD)?
Regarding usefulness, it is the second most interesting cannabinoid for medical purposes after THC (tetrahydrocannabinol).
Recent research, including clinical investigation, confirms that CBD is as important as THC and is in some cases even more important.
Unlike THC, CBD has no noticeable psychoactive effects and works synergistically with THC because it works mainly in the immune system and the peripheral nervous system instead of the central nervous system and as such does not cause intoxication.
CBD strengthens the healing effects of THC while mitigating its psychoactive effects.
Read our full article on What Is CBD (Cannabidiol)
The bottom line is that feeding your endocannabinoid system is a good way to promote wellbeing and everyday health!
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FOOD AND DRUG ADMINISTRATION (FDA) DISCLOSURE
These statements have not been evaluated by the FDA and are not intended to diagnose, treat or cure any disease. Always check with your physician before starting a new dietary supplement program.