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Cannabinoids & The Endocannabinoid System

 

 

 

 

When people think of cannabinoids, the first thing that comes to most peoples’ minds are cannabis, and cannabinoid compounds such as THC and CBD.  But, what most people are unaware of is that cannabinoids do not always equal cannabis, and that all vertebrates have their own biological system for creating and processing cannabinoids.  

This system is called the endocannabinoid system (ECS), and it is involved in controlling, modulating and mediating, a variety of biological systems ranging from fundamental physiological responses such as appetite, pain modulation, digestion and reproduction, to higher-order cognitive functioning such as motor learning, stress responses, mood, and even memory.

The ECS is also thought to play a pivotal role in maintaining a state of homeostasis within the body - the concept that most biological and physiological systems are actively regulated in order to maintain an optimal set of intra-cellular and microenvironmental conditions.  Think of it as a type of “Goldilocks zone” where everything is just right so that cells can function at optimum levels of performance and maintaining overall health and wellness within the body.

But what is the ECS, and how does it work?

 

The Endocannabinoid System 101

In it’s most basic form, the Endocannabinoid System (ECS) is primarily made up of:

  1. Endocannabinoids;
  2. CB1 and CB2 receptors, and;
  3. Metabolic enzymes.

 

Endocannabinoids

It might be surprising to know that, even without ever being exposed to cannabis or cannabis related compounds, each one of us have cannabinoids present in out systems to help activate and regulate the ECS.  The reason for this is that our bodies make its very own cannabinoids, called endocannabinoids, that are made on demand and on location.

Endocannabinoids are a special type of neurotransmitter called retrograde neurotransmitters which, in plain English means is that endocannabinoids can work like a kind of dimmer switch that not only sends signals down the signalling pathway, but that can also travel back up that same signalling pathway and “dim” further communication  from happening. So say for instance you are experiencing pain, endocannabinoids have the ability to travel back up the neural pathway, and tell the cells to stop producing the neurotransmitters that produce the pain signal and thus stopping the sensation of pain.

To date, there are five known endocannabinoids: anandamide (AEA); 2-arachidonoylglycerop (2-AG); O-arachidonoyl ethanolamine (O-AEA); 2-arachidonyl glyceryl (Noladin); and the most recently discovered N-Arachidonoyl dopamine (NADA).

Cannabinoid Receptors

For endocannabinoids to send signals from one cell to another, they need to bind to cannabinoid receptors to help send those signals between different cells in the body.  To date, there are two major receptors that have been identified.  These are the CB1 and the CB2 receptors.

CB1 Receptors

CB1 receptors are activated by the endocannabinoids AEA and 2-AG, as well as by phytocannabinoids or its synthetic counterparts 3.  CB1 receptors are mostly found within the brain and central nervous system but are also found in the lungs, gastrointestinal tract, liver, and kidneys 4,.

The CB1 receptor along with AEA and 2-AG is thought to be responsible for maintaining homeostasis by modulating the amount of other neurotransmitters that are being released, helping to prevent and excessive amount of neuronal activity to take place.  In addition, CB1 receptors are also believed to be particularly involved with reducing pain and inflammation 5, the inhibition of excessive arousal, helping to reduce things such as anxiety and aggression 6, as well as being involved in the mediation of short-term depression 7.  CB1 receptors also affect appetite and digestion 8, 9; is involved with motor control 10, 11; and have also been found to help reduce drug seeking behaviour 12, 13, 14.

CB2 Receptors

CB2 receptors are predominantly found in the immune system although they are also present in the spleen, tonsils, thymus gland, and even retinal cells 4.  The main endocannabinoid that binds to CB2 receptors is 2-AG.

CB2 receptors are intricately involved in a variety of modulatory functions, including immune function and response, cell death, and cell migration during tissue development 4, 15.  In addition, they have also been found to modulate intestinal inflammatory response 16, 17 which has made this an interesting area of study for the treatment of gastrointestinal illnesses such as Chron’s disease, inflammatory bowel diseases, as well as ulcerative colitis 17, 18.

Metabolic Enzymes

The two major enzymes are Fatty acid amide hydrolase (FAAH) which breaks down AEA, and Monoacylglycerol lipase (MAGL) that breaks down 2-AG, ensuring that endocannabinoids are only used when needed, and no longer than necessary.  This differentiates endocannabinoids from other molecular signals such as hormones or other neurotransmitters which can persist in the body, or can be packaged for later use.

 

Phytocannabinoids, Hemp CBD Oil & the Endocannabinoid System

Although they differ in chemical composition, several recent studies show that there is a marked overlap between the way in which endocannabinoids and phytocannabinoids interact with the ECS 19.  Phytocannabinoids are plant based cannabinoids and are most abundantly found in the hemp and cannabis plants.  Phytocannabinoids include compounds such as tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinoid (CBN) and so on.

As with most other biological systems and because endocannabinoids are not stored for later, nor are they sent from one location to another, the ECS can become dysfunctional with either too much or too little endocannabinoids being available.  When phytocannabinoids such as CBD are introduced back into the system, it helps to kick-start the ECS again, regulating the central nervous system, and helping to restore homeostasis within the body.

 

CBD especially seems to have an incredible and wide-spread influence on the ECS, with its effects being systemic in nature.  The reason for this is that unlike other cannabinoids such as THC, CBD does not bind with either the CB1 or CB2 receptors.  Instead, it stimulates activity in both receptors, resulting in changes within any cells that contain either receptor 19, 20, 21.

In addition to impacting the ECS, CBD also affects the body in other ways by binding onto non-ECS receptors, and even inhibiting certain genes.  For instance, CBD is known to bind to the TRPV-1 receptor, helping to control body temperature, pain perception and inflammation, further accounting for the analgesic and anti-inflammatory properties of CBD.  CBD also activates serotonin receptors which is why scientists suspect CBD helps relieve the symptoms of serotonin related disorders such as depression, anxiety and even ADHD.  Moreover, recent studies also found that CBD has the power to inhibit the cancer causing ID-1 gene, making CBD a wonderful supplement for the possible prevention of cancers such as breast, brain and pancreatic cancer when caused by the expression of this gene 22, 23.

Take Home Message

The ECS plays a pivotal role in the body, with CB1 and CB2 receptors being distributed throughout the body.  Being involved in regulating a variety of physiological and cognitive process including, appetite, pain-sensation, mood, memory, immune function, memory and even locomotor activity and motivational salience towards rewards, when this system goes haywire, the effects can be far reaching, often causing disease and disfunction. 

Phytocannabinoids such as THC and CBD are not only proving to be powerful therapeutic agents in and of themselves, but also impact on the ECS itself.  Especially when one considers the impact CBD has on the ECS as well as other areas of the body, it becomes evident that this cannabinoid in particular can potentially be exceedingly useful in treating a variety of medical conditions.  Medical research involving the potential uses of CBD is ongoing, with an increasing body of evidence suggesting that the list of conditions CBD could potentially treat, growing exponentially.

minds are cannabis, and cannabinoid compounds such as THC and CBD.  But, what most people are unaware of is that cannabinoids do not always equal cannabis, and that all vertebrates have their own biological system for creating and processing cannabinoids.  

This system is called the endocannabinoid system (ECS), and it is involved in controlling, modulating and mediating, a variety of biological systems ranging from fundamental physiological responses such as appetite, pain modulation, digestion and reproduction, to higher-order cognitive functioning such as motor learning, stress responses, mood, and even memory.

The ECS is also thought to play a pivotal role in maintaining a state of homeostasis within the body - the concept that most biological and physiological systems are actively regulated in order to maintain an optimal set of intra-cellular and microenvironmental conditions.  Think of it as a type of “Goldilocks zone” where everything is just right so that cells can function at optimum levels of performance and maintaining overall health and wellness within the body.

But what is the ECS, and how does it work?

 

The Endocannabinoid System 101

In it’s most basic form, the Endocannabinoid System (ECS) is primarily made up of:

  1. Endocannabinoids;
  2. CB1 and CB2 receptors, and;
  3. Metabolic enzymes.

 

Endocannabinoids

It might be surprising to know that, even without ever being exposed to cannabis or cannabis related compounds, each one of us have cannabinoids present in out systems to help activate and regulate the ECS.  The reason for this is that our bodies make its very own cannabinoids, called endocannabinoids, that are made on demand and on location.

Endocannabinoids are a special type of neurotransmitter called retrograde neurotransmitters which, in plain English means is that endocannabinoids can work like a kind of dimmer switch that not only sends signals down the signalling pathway, but that can also travel back up that same signalling pathway and “dim” further communication  from happening. So say for instance you are experiencing pain, endocannabinoids have the ability to travel back up the neural pathway, and tell the cells to stop producing the neurotransmitters that produce the pain signal and thus stopping the sensation of pain.

To date, there are five known endocannabinoids: anandamide (AEA); 2-arachidonoylglycerop (2-AG); O-arachidonoyl ethanolamine (O-AEA); 2-arachidonyl glyceryl (Noladin); and the most recently discovered N-Arachidonoyl dopamine (NADA).

Cannabinoid Receptors

For endocannabinoids to send signals from one cell to another, they need to bind to cannabinoid receptors to help send those signals between different cells in the body.  To date, there are two major receptors that have been identified.  These are the CB1 and the CB2 receptors.

CB1 Receptors

CB1 receptors are activated by the endocannabinoids AEA and 2-AG, as well as by phytocannabinoids or its synthetic counterparts 3.  CB1 receptors are mostly found within the brain and central nervous system but are also found in the lungs, gastrointestinal tract, liver, and kidneys 4,.

The CB1 receptor along with AEA and 2-AG is thought to be responsible for maintaining homeostasis by modulating the amount of other neurotransmitters that are being released, helping to prevent and excessive amount of neuronal activity to take place.  In addition, CB1 receptors are also believed to be particularly involved with reducing pain and inflammation 5, the inhibition of excessive arousal, helping to reduce things such as anxiety and aggression 6, as well as being involved in the mediation of short-term depression 7.  CB1 receptors also affect appetite and digestion 8, 9; is involved with motor control 10, 11; and have also been found to help reduce drug seeking behaviour 12, 13, 14.

CB2 Receptors

CB2 receptors are predominantly found in the immune system although they are also present in the spleen, tonsils, thymus gland, and even retinal cells 4.  The main endocannabinoid that binds to CB2 receptors is 2-AG.

CB2 receptors are intricately involved in a variety of modulatory functions, including immune function and response, cell death, and cell migration during tissue development 4, 15.  In addition, they have also been found to modulate intestinal inflammatory response 16, 17 which has made this an interesting area of study for the treatment of gastrointestinal illnesses such as Chron’s disease, inflammatory bowel diseases, as well as ulcerative colitis 17, 18.

Metabolic Enzymes

The two major enzymes are Fatty acid amide hydrolase (FAAH) which breaks down AEA, and Monoacylglycerol lipase (MAGL) that breaks down 2-AG, ensuring that endocannabinoids are only used when needed, and no longer than necessary.  This differentiates endocannabinoids from other molecular signals such as hormones or other neurotransmitters which can persist in the body, or can be packaged for later use.

 

Phytocannabinoids, Hemp CBD Oil & the Endocannabinoid System

Although they differ in chemical composition, several recent studies show that there is a marked overlap between the way in which endocannabinoids and phytocannabinoids interact with the ECS 19.  Phytocannabinoids are plant based cannabinoids and are most abundantly found in the hemp and cannabis plants.  Phytocannabinoids include compounds such as tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinoid (CBN) and so on.

As with most other biological systems and because endocannabinoids are not stored for later, nor are they sent from one location to another, the ECS can become dysfunctional with either too much or too little endocannabinoids being available.  When phytocannabinoids such as CBD are introduced back into the system, it helps to kick-start the ECS again, regulating the central nervous system, and helping to restore homeostasis within the body.

 

CBD especially seems to have an incredible and wide-spread influence on the ECS, with its effects being systemic in nature.  The reason for this is that unlike other cannabinoids such as THC, CBD does not bind with either the CB1 or CB2 receptors.  Instead, it stimulates activity in both receptors, resulting in changes within any cells that contain either receptor 19, 20, 21.

In addition to impacting the ECS, CBD also affects the body in other ways by binding onto non-ECS receptors, and even inhibiting certain genes.  For instance, CBD is known to bind to the TRPV-1 receptor, helping to control body temperature, pain perception and inflammation, further accounting for the analgesic and anti-inflammatory properties of CBD.  CBD also activates serotonin receptors which is why scientists suspect CBD helps relieve the symptoms of serotonin related disorders such as depression, anxiety and even ADHD.  Moreover, recent studies also found that CBD has the power to inhibit the cancer causing ID-1 gene, making CBD a wonderful supplement for the possible prevention of cancers such as breast, brain and pancreatic cancer when caused by the expression of this gene 22, 23.

Take Home Message

The ECS plays a pivotal role in the body, with CB1 and CB2 receptors being distributed throughout the body.  Being involved in regulating a variety of physiological and cognitive process including, appetite, pain-sensation, mood, memory, immune function, memory and even locomotor activity and motivational salience towards rewards, when this system goes haywire, the effects can be far reaching, often causing disease and disfunction. 

Phytocannabinoids such as THC and CBD are not only proving to be powerful therapeutic agents in and of themselves, but also impact on the ECS itself.  Especially when one considers the impact CBD has on the ECS as well as other areas of the body, it becomes evident that this cannabinoid in particular can potentially be exceedingly useful in treating a variety of medical conditions.  Medical research involving the potential uses of CBD is ongoing, with an increasing body of evidence suggesting that the list of conditions CBD could potentially treat, growing exponentially.