Location and function of CB1 & CB2 endocannabinoid receptors in the human body
What is the Endocannabinoid System?
The endocannabinoid system (ECS) can be formed in almost every part of our body, but especially the nervous system and immune system. A healthy endocannabinoid system enables homeostasis. This simply means the ECS balances our cells and organs – it’s the Yin and Yang of the body.
In order to maintain this balance, the endocannabinoid system (ECS) regulates physical and emotional processes like appetite and mood.
It does this with substances called endocannabinoids, which are neurotransmitters. Simply put, neurotransmitters are “chemical commands” that one cell releases to tell another cell what to do, creating a specific biological response
The net effect of these commands is called endocannabinoid tone. Tonic frameworks in the body have resting movement, so cannabinoid receptors are continually enacted by a low degree of anandamide generation. Since the framework has a resting action of more prominent than 0, that implies that its action can be turned down! This is the manner by which the ECS can control guidelines; in the event that it couldn’t diminish its action from the gauge, at that point it wouldn’t have the option to advance equalization when a procedure lessens somewhat.
Do I have an endocannabinoid system?
All mammals have an endocannabinoid system (ECS). Its discovery has been a 40-year journey and exposes every day. However, Researchers discovered the endocannabinoid system while attempting to pinpoint exactly how THC produces its effects; The THC compound is present in cannabis which causes the psychoactive effects (the high) associated with marijuana.
Over the years what the know is that the endocannabinoid system, ECS for short, is a signaling system that allows our cells and organs to communicate with each other in order to balance overall activity and energy consumption. This results in what we call homeostasis: a healthy state of balance within our body.
What is homeostasis?
Homeostasis is internal balance or stability amid changing external conditions.
The term homeostasis is very broad.
It refers to general organism-level factors, like body temperature, which is affected by the external environment.
Homeostasis also refers to specific cellular factors like oxidative stress, which affects the activity levels of other cells in the immediate microscopic vicinity.
The endocannabinoid system – a complex, scaled communication network – maintains homeostasis and balance across the different systems of our body.
What Are Endocannabinoids?
Endocannabinoids are chemical messengers.
The word endocannabinoid means “cannabinoid produced inside”; it refers to cannabinoids that form inside our bodies.
Endocannabinoids are signaling molecules almost use by all of our cells.
Chemical release by one cell in order to produce some effect in a nearby cell, like when you use a remote control to turn on the TV.
Every chemical signal has a predictable and consistent effect depending on the cell-type and chemical environment, just like the power button on your remote turns the TV on, but doesn’t affect the volume or the menu because there are different buttons – neurotransmitters – for those actions. Hormones like estrogen, and neurotransmitters such as dopamine and serotonin, are all common examples of chemical signals or messengers.
The process of cellular communication involves chemical signals and the receptors which they act on. In the ECS, there are 5 relatively name as endocannabinoids, although 2-AG and anandamide are also famous. Specifically, a cell releases endocannabinoids to alter the activity levels of a nearby cell which is affecting it in some way.
To think of this relationship
imagine a teacher giving information to her students. If she’s going too fast, the students will ask her to slow down.
And if the teacher and her students were cells in our body, the endocannabinoid system would be the students’ ability to ask the teacher to slow down. If this ability restricts in some way, then problems with the students’ understanding will occur.
Similarly, when the ECS fails to allow cells to communicate, health problems arise.
What Are Endocannabinoids?
When the ECS becomes overactive or underactive, endocannabinoid tone can no longer promote homeostasis.
Without the ECS to maintain balance, systems of the body begin to malfunction. This condition is called Clinical Endocannabinoid Deficiency (CECD).
CECD leads to many common health problems that seem to arise without cause.
CECD Symptoms Can Include:
- Chronic pain
- Autoimmune disorders
- Depression and other mood disorders
What causes Clinical Endocannabinoid Deficiency?
CECD occurs when your body loses the ability to maintain a healthy endocannabinoid tone. This can be formed by dietary and lifestyle factors, or other disorders. Cannabis plants produce compounds called phytocannabinoids, which interact with our endocannabinoid system to promote balance and maintain a healthy endocannabinoid tone. Below is an overview of the endocannabinoids that have been discovered so far, and what we know about their activities and responsibilities.
Anandamide (N-Arachidonoyl Ethanolamide)
Anandamide, also recognizes as AEA, was the first endocannabinoid discovered back in 1991. The word anandamide comes from the Sanskrit word for bliss: “Ananda”.
Anandamide is a partial agonist of CB1 receptors, which forms in the central nervous system. It’s a weaker agonist of CB2 receptors, which are found in the periphery and immune system.
An agonist is any chemical compound that activates a given receptor.
In the case of anandamide, it binds to and activates CB1 and CB2 cannabinoid receptors. However, it only partially activates them. It’s about 40% as potent as 2-AG at cannabinoid CB1 receptors.
2-AG, or 2-arachidonoyl glycerol, is another major endocannabinoid in addition to anandamide. It came across after anandamide so it’s less-commonly recognize, but 2-AG’s role is equally important.
Unlike anandamide, 2-AG is a full agonist of CB1 and CB2 receptors. For some context, 2-AG is strongly associates with the feeling of a “runner’s high,” the sense of euphoria reported by athletes following intense workouts.
Virodhamine (O-Arachidonoyl Ethanolamine)
In 2002, another endogenous compound with activity at cannabinoid receptors was come across: virodhamine. It has the same chemical formula as anandamide, but its effects are slightly less.
By binding to cannabinoid receptors at the same rate as the other endocannabinoids, but producing a significantly smaller effect, virodhamine reduces the overall activation of cannabinoid receptors.
Researchers believe this is just one of the many regulatory mechanisms innate within the endocannabinoid system: virodhamine limits the effects of the stronger endocannabinoids in a process name as competitive antagonization.
2-Arachidonyl glyceryl ether, 2-AGE, or simply noladin ether, is an endocannabinoid that was discovered in 2001 by a team led by Raphael Mechoulam, the scientist who discovered THC and many other phytocannabinoids (plant-derived cannabinoids).
Structurally, 2-AGE is almost identical to 2-AG. Similar to the relationship between anandamide and virodhamine, 2-AG and 2-AGE have nearly identical chemical formulas but are arranged in a slightly different manner, producing slightly different effects.
2-AGE is an agonist of both cannabinoid receptors, in spite of the fact that it has multiple times the liking (fascination) for CB1 receptors contrasted with CB2. Hence, it goes about as an agonist at CB1 receptors, yet has the net impact of decreasing the movement of CB2 receptors, by viewing for spots at the receptor with more grounded agonists.
N-Arachidonoyl Dopamine (NADA)
In 2000, NADA was discovered as an agonist of CB1 receptors and TRPV1 receptors, but not of CB2. It is 40 times more attracted to CB1 than CB2, and it’s the body’s primary endogenous TRPV1 agonist.
TRPV 1 receptors are located on sensory nerves and they react to chemicals that are painful to touch. NADA competes with these painful chemicals for a spot at the pain receptor, but it doesn’t cause a pain response. They protect us from chemical pain by blocking the receptors where the pain would be registered.
It is (NADA) is the combination of arachidonic acid, found in all endocannabinoids, with dopamine, one of the brain’s primary neurotransmitters. It is the strongest endogenous CB1 agonist, and it can also be applied as a dietary supplement.
What Are Cannabinoid Receptors?
In biological organisms like humans and cannabis plants, long chains of DNA (deoxyribonucleic acid) are included in every single cell. DNA is shaped like a twisting ladder, but instead of 10 or 20 rungs, the DNA ladder in each of your individual cells has about 3,000,000,000 (billion) “rungs”, or base pairs.
The order of these base pairs determines our genes, and our genes work by getting turned into one of over 50,000 different proteins which each have a distinct and important purpose.
are the “machines” which carry out all of the different processes within our cells. They are classified by their purpose.
Receptors are a class of proteins that become fixed in cell membranes: they’re the membrane-bound proteins. This is key to their function, because part of the receptor exposes to the outside of the cell, while the rest resides within the cell.
The piece of the receptor which is situated outside of the cell reacts to ecological upgrades, for example, warmth, light, or certain synthetic substances (recollect concoction envoys?). The piece of the receptor reaching out inside the cell at that point delivers an impact inside the cell on the outer boosts. Each different receptor is receptive to a unique stimulus, name as an agonist.
Cannabinoid CB1 receptors
Cannabinoid type 1 receptors (CB1) are found in the brain and central nervous system of all mammals. This receptor was first discovered as researchers sought to decode the effects of THC, the main psychoactive ingredient in marijuana. It was found that Δ9-THC potently binds to CB1 receptors, and thus mimics the effects of the endogenous cannabinoids.
Although it only recently came across, the importance of CB1 in the central nervous system demonstrates by the fact that there are more CB1 receptors than all other receptors, merges: more than half of all receptors in your brain are cannabinoid receptors.
Working of Cannabinoid CB1 Receptors
When activated, CB1 receptors drastically reduce the activity of important cellular processes that require for the core functionality of cells. Importantly, these core processes repeat in many different types of cells, so the endocannabinoid system is able to use the same mechanism to control the activity of drastically different types of cells.
The core function of neurons is to produce an action potential, the scientific term for when a neuron “fires”. CB1 activation causes an influx of calcium ions into the neuron, which temporarily prevents the formation of such an action potential; CB1 activation prevents the neuron from firing. This can have many different effects depending on the region of the brain which is being inhibited by CB1 activation.
Cannabinoid CB2 receptors
Cannabinoid type 2 receptors (CB2) are primarily concentrated in the immune system of mammals as opposed to the concentration of CB1 receptors in the CNS. CB2 receptors are just 44% indistinguishable from CB1 receptors, however, they have about the equivalent cell reason, the essential contrasts being the kind of cell that communicates them and the particular mixes which initiate them.
Similar to CB1 in the brain, CB2 is one of the most abundant receptors in immune tissue. Besides, the CB2 movement is influenced by numerous disarranges of the invulnerable starting point. Analysts accept this relationship is liable for probably a portion of the restorative properties of the phytocannabinoids which interface with CB2 receptors.
As a cannabinoid receptor, CB2 inhibits the activity of fundamental processes which many different kinds of cells use to carry out their core function. The core functionality of immune cells (B cells) is to recognize specific chemical markers of injury or infection – called antigens – and activate “soldier” or “doctor” cells (T cells) by releasing chemical messengers known as chemokines.
CB2 activation reduces the ability of B cells to produce chemokines.
It also raises the threshold amount of chemokines required to “activate” the T cells, which create inflammation and can subsequently harm healthy tissue if not properly balanced and regulated by processes like CB2 activation.
GPR-55 (Orphan G-protein coupled receptor 55)
Another receptor, a conclusive limit of which isn’t totally clear, yet the nearness of which has been ordinary for an impressive time allotment is the GPR-55 receptor. It frames all through all tissues, and it seems to have a job in intervening “irritation”, Which causes torment by the enactment of safe cells.
Aches and pains associated with a workout or a moderate cold/flu are not actually lead to by these things. Or maybe, the invulnerable reaction to muscle harm or contamination like this season’s flu virus causes the arrival of exacerbates that enact torment receptors on tangible nerves. It is thought that GPR-55 is one of these receptors, and cannabinoids regulate pain by competing with the painful immune chemicals for a spot activating a GPR-55 receptor.
Despite CB1, CB2, and GPR-55, distinct sorts of receptors respond to and interface with endocannabinoids and plant cannabinoids. The discovery of additional receptors that operate within the endocannabinoid system continuously expands our understanding of how the ECS works.
Peroxisome Proliferator-activated receptors (PPARs)
control the expression of genes depending on cell-type. They implicate in cancer growth and activation of immune cells. Endocannabinoids interact with PPARs to modulate the expression of certain genes bases on the requirements of the cell’s environment.
Transient receptor potential vanilloid type 1 receptors (TRPV1)
The form on sensory nerves throughout the peripheral nervous system. TRPV 1 receptors recognize both high temperatures as well as chemicals that “burn”, like the primary compound responsible for the taste of chili peppers: capsaicin.
They are an instrumental part of human pain perception, and endocannabinoid regulation of TRPV1 is a negative feedback mechanism that maintains the sensitivity of this receptor by competing with painful stimuli for spots at TRPV1 receptors, a process called competitive antagonization.