Endocannabinoids which are responsible for communication between cells, tissues and organs are produced naturally in our body. They act as a ‘brake’ that soothes our nervous system and prevents the overload of cells especially when we are under severe stress, are ill or in pain.
Most research has been conducted on two types of receptors which cannabinoids recognise, binds to and transfers information and tasks to neighbouring cells. Most commonly, tetrahydrocannabinol (THC) binds to CB1 receptors located primarily in the central nervous system while cannabidiol (CBD) binds to CB2 receptors located in tissues connected with the immune system.
If our body is frequently under stress and is unable to produce enough of its own cannabinoids, they can also be taken externally in the form of hemp resin or drops. Phytocannabinoids, which are extracted from the cannabis plant, are able to bind to the same receptors as endocannabinoids and consequently the cells recognize and accept them and the immune system is brought back into balance.
What are cannabinoids?
WHAT IS CANNABIDIOL (CBD)?
Cannabidiol (CBD), found in Cannabis plant tips, is one of 85 active cannabinoids identified in hemp resin. More than 40 percent of all phytocannabinoids in the plant extract is CBD which is present in almost all varieties of hemp.
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.
WHAT ARE ENDOCANNABINOIDS?
Endocannabinoids are cannabinoids that are produced by our body and are able to activate cell membrane cannabinoid receptors. They are named after the cannabinoids in hemp plant as their chemical structure is very similar.
Endocannabinoids serve as intercellular lipid messengers, 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 are lipophilic molecules, amides and esters formed from fatty acids, which do not dissolve well in water. Endocannabinoids are integral components of cell membrane, synthesized on demand by enzymes and not stored for later use. Since endocannabinoids are hydrophobic molecules, they cannot travel long distances through an aqueous medium without external assistance and therefore only act within the vicinity of target cells, i.e. locally.
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).
OUR ENDOCANNABINOID SYSTEM
WHAT EFFECTS DO ENDO- AND PHYTOCANNABINOIDS HAVE ON OUR BODY?
Endocannabinoids are not stored in the body – FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase) enzymes are needed for their production and decomposition. Endocannabinoids are not formed spontaneously, but require an appropriate physiological or pathological stimulus. If there is a disorder in the synthesis of endocannabinoids in the body, from where health problems may arise, suitable plant cannabinoid can be used as a substitute. Most synthetic pharmaceutical drugs for depression, autoimmune inflammation, cholesterol, asthma and painkillers take effect on the G protein of GPCR receptor, which also includes CB1, CB2, GPR55, GPR119 receptors. Therefore, they activate the same signal transduction pathways in the body as the phytocannabinoids from hemp.
Animal and plant cannabinoids can only be effective if they bind to cannabinoid receptors. The receptors are small proteins that are embedded in every cell membrane. The binding of a specific molecule (like a key) to these receptors, leads to cellular changes.
So far, 4 receptors have been investigated, bound to GPCR (G protein-coupled receptor) protein receptors; CB1, CB2, GPR55, GPR119 and the channel TRPV1. 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.
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