What is the Endocannabinoid System & How does it Work?

What is the Endocannabinoid System? | on ItsHemp
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Talking about HempCBD, or cannabis at large, is incomplete without talking about the ECS. By now we know by our hearts that the THC and CBD in the cannabis plants interact with the ECS in the human body.

But do we really know what the ECS is? How does it work? What exactly does it do? This article attempts to answer these questions and understand how does CBD work by interacting with the ECS.

The Endocannabinoid System

What is the Endocannabinoid System?
What is the ECS made of?
– Endocannabinoids
– Cannabinoid Receptors
– Enzymes
Endocannabinoid Deficiency
How was the ECS discovered?
– A brief history of the ECS
Tid-bits about the Endocannabinoid System
How does the ECS work?
– THC and the ECS
– CBD and the ECS
Treatment Potential
A Word from ITSHEMP
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What is the Endocannabinoid System?

The Endocannabinoid System is a biological system in the human body. Though still under preliminary research, the system plays an imperative role in regulating several physiological and cognitive processes. These include appetite, mood, memory, fertility, pregnancy etc. It comprises a vast network of chemical signals and cellular receptors—all densely packed throughout the brain and body.

The ECS has emerged as an important neuromodulatory system over the last 25 years. It regulates various nervous, cardiovascular, and immune system functions inside cells. While experts are still trying to completely understand the ECS, so far, we know that it plays an important role in regulating many crucial functions and processes in the body. These include sleep, appetite, memory, mood, reproduction and fertility, etc.

In simple terms, the ECS helps in fine-tuning most of our vital physiological functions. It aids in modulating the regulation of homeostasis across all major body systems ensuring that all the systems work in good harmony with each other. Ever wondered how, with all the complex cell signals, genetic mutations, and outside influences, our body manages to stay at homeostasis? The answer is the endocannabinoid system.

What does endocannabinoid mean?

The term endocannabinoid is the sum of:

  • endo, meaning endogeneous i.e. something that has an internal cause or origin
  • cannabinoid, meaning any group of closely related compunds which include cannabinol and the active constituents of cannabis

That is to say, endocannabinoids are cannabis-like substances that naturally occur inside the human body.

What is the ECS made of?

The endocannabinoid systems is made up of 3 components:

  • Endocannabinoids: The messengers of the ECS. They are They are produced throughout our body. The two key endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The former is involved in appetite, memory, and pregnancy. The latter plays an imperative role in our emotional state and maintaining cardiovascular health. Our body produces endocannabinoids as required. It is, therefore, difficult to know what the typical level for each is.
  • Cannabinoid Receptors: Receptors with which cannabinoids and endocannabinoids bond with. These are found in both the central nervous system and the peripheral nervous system. Endocannabinoids bind to these receptors to signal the ECS to perform a particular function. There are two main endocannabiniod receptors:
    • CB1 Receptors: mostly found in the brain and the central nervous system. Depending on their  location in the brain, they help moderate memory, mood, motor function, and/or one’s perception of pain. It is the CB1 receptors that cause the high in the brain when we smoke marijuana. CB2 receptors help in moderating inflammation and our immune response to pathogens.
    • CB2 Receptors: mostly found in the peripheral nervous system, especially in the immune cells.

      Endocannabinoids can bind to either of the receptors resulting in different effects. For example, some endocannabinoids might target the CB1 receptors in a spinal nerve to provide relief from pain. Others might bind to CB2 receptors in the immune cells to target inflammation.
  • Enzymes: These help break down endocannabinoids and cannabinoids, once they’ve carried out their function. There are two main enzymes responsible for this:
    • fatty acid amide hydrolase, which breaks down AEA
    • monoacylglycerol acid lipase, which typically breaks down 2-AG

Our body activates the endocannabinoid system with precision so as to impact only what it needs to. For example, if there is a problem in your reproductive hormones, the ECS will work to regulate them without altering your immune or digestive system. Once the endocannabinoids have brought things into balance, specific enzymes come along to break them down. This prevents them from upsetting the balance in the opposite direction. Through the cannabinoid receptors, the ECS helps regulate important functions such as appetite, digestion, inflammation, immune function, mood, sleep, motor control, reproduction and fertility, temperature regulation, memory, pain, pleasure, etc.

Endocannabinoid Deficiency

Medical science has also discovered a number of conditions seemingly related to the dysregulation of the ECS. This is called Clinical Endocannabinoid Deficiency (CECD). It is not a disease in itself but an umbrella term that covers multiple conditions with this common feature. Some common conditions in which CECD plays a major role, as supported by evidence include Fibromyalgia, Migraine, and Irritable Bowel Syndrome.

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These conditions are sometimes called functional conditions or central sensitivity syndromes. They tend to be resistant to most treatments which is why researchers are drawn towards exploring cannabs-based treatments, such as CBD oil, for them. Functional conditions generally involve more than one system, which makes sense considering the number of areas that the ECS influences.

For instance, Fibromyalgia involves central and peripheral nervous systems, the endocrine system, the immune system, and the digestive system. These seem like a group of unrelated problems until you focus on homeostasis and the ECS.

How was the ECS discovered?

The discovery of the endocannabinoid system was a result of the discovery of CB1 and CB2 receptors in the body when scientists were trying to understand the effects of cannabis on the human body. Scientists managed to isolate numerous phytochemicals (called phytocannabinoids) from the cannabis plants.

In the attempt of uncovering the metabolic pathways of phyto-cannabinoids and endocannabinoids, scientists discovered an unknown molecular signalling system within the human body involved in manufacturing and using the body’s own form of cannabinoids. This system was named the Endocannabinoid System.

A Brief History of the ECS

In 1998, one of the world’s leading cannabinoid scientists, Vincenzo Di Marzo, stated that the physicological processes in the human body such as mood, appetite, sleep, memory, and pain sensation are under the control of a biological regulatory system wired to keep the body in balance. Named after the cannabis plant, the endocannabinoid system performs different tasks in different tissues. But its aim is always the same: homeostasis.

A critical step in the discovery of the ECS was taken in 1964 when Dr Raphael Mechoulam, the godfather of cannabis research, first identified and isolated THC and CBD. These cannabinoids were called phytocannabinoids because they were naturally occurring in plants.

The ECS was first defined in 1990 when molecular biologist Lisa Matsuda and her team at the National Institute of Mental Health identified a THC-sensitive receptor in lab rat brains. Shortly after this, Mechoulam’s research led to the discovery of two endocannabinoids, AEA and 2-AG.

These were called endocannbinoids because they were naturally produced in the body by the brain. They bind to cannabinoid recepors on target cells throughout the body and trigger a cellular response which is either amplified or dimished as metabolic enzymed destroy or make more endocannabinoids. This activity leads to diverse effects ranging from anti-inflammatory responses to euphoria.

These discoveries set into motion research exploring the ECS. It has been established that endocannabinoids play a role in the pathology of many disorders while also serving a protective role in many medical conditions.

Drug modulating the ECS can possibly be used to treat diseases like Tourette’s syndrome, Alzheimer’s, Hunginton’s disease, Parkinson’s, metabolic syndrome and related diseases, cancer, ardiovascular disorders, glacouma, epilepsy, MS, inflammation, anorexia, and chronic pain.

Tid-bits about the Endocannabinoid System

Here are some interesting facts about the ECS:

  • All animals have an endocannabinoid system: All vertebrates and invertebrates are known to have an ECS. Sea-squirts, an animal which evolved over 600 million years ago, are the most primitive animal found to express cannabinoid receptors.
  • Endocannabinoid Receptors are the most plentiful neuro-modulatory receptors in the body: It is believed that the total number of endocannabinoid receptors in the body is greater than all other neuro-modulatory receptors found in the body combined.
  • Exercise and diet help boost the ECS: Scientific studies suggest that prolonged aerobic exercise can increase the level of anandamide (the feel good endocannabinoid). Where diet is concerned, increasing your intake of omega 3 helps support the endocannabinoid brain signalling.
  • ECS plays a crucial role in many diseases: Scientists observe that in a number of diseases such as rheumatoid arthritisneurodegenerative disorders, and cancer, the ECS activity of the human body changes. These findings suggest that the ECS may be an efficate target for restoring balance in the body and stimulating good health.

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How does the Endocannabinoid System work?

The ECS is not like the other signalling systems in the body. The neurons, for example, communicate with each other and the rest of the body through chemical messages. Typically, neurotransmitters are released from a neuron (the presynaptic cell), travel across the synapse, and attach themselves to specific receptors (the postsynaptic cell). This puts the receiving neuron into action and triggers a set of events allowing the messages to be passed along.

The endocannabinoid system, however, works in a backward direction. The postsynaptic neuron is activated first causing the cannabinoids (i.e. the messengers of the ECS) to be produced on demand from the fat cells already present in the neuron. These are then released from the postsynaptic neuron and travel backward to the presynaptic neuron attaching to cannabinoid receptors.

What does this mean?

This means that cannabinoids act on presynaptic cells. That is to say, they can control what happens when the cells are activated. They limit the amount of neurotransmitter to be released thus affecting the way messages are sent, received, and processed.

Endocannabinoids and phytocannabinoids (those found in cannabis such as CBD and THC) bind and interact with each other and many other receptors in the body. If receptors are locks, cannabinoids are the key. Once engaged, cannabinoid receptors set off process to slow down the nerve signal. Different cannabinoid receptor interactions have different effects on the body and help regulate a number of important functions.

How does THC interact with the ECS?

THC is the chemical compound in cannabis responsible for the high. On entering the body, THC interacts with the ECS by binding to cannabinoid receptors. THC can bind to both CB1 and CB2 receptors. This allows it to have wide range of effects on the mind and body. For example, THC can reduce pain and stimualte appetite. But it can also cause paranoia and anxiety in some cases.

How does CBD interact with the ECS?

CBD is the second major cannabinoid present in the cannabis plant. It is famous for its many therapeutic effects, all without any intoxication. CBD does not bind to the CB1 and CB2 receptors like THC. It actually works the other way around by inhibiting the breakdown of certain cannabinoids in a particular receptor. For example, CBD reduces the action of the enzymes that will break down anandamide in the body. This leads to a higher concentration of anandamide. And since it has a calming effect on the brain, higher concentration allows CBD’s use in treating stress and anxiety.

Treatment Potential

Cannabinoids such as CBD and THC are being researched as potential treatments for all kinds of conditions. Research tells us that CBD can prove to be an effective remedy for illnesses that are:

  • Physical: e.g. Arthritis, menstrual pain, muscle inflammation
  • Psychological: e.g. Anxiety, depression, schizophrenia
  • Sleep Disorders: e.g. Insomnia, sleep apnea
  • Neurodegenerative Disorders: e.g. Alzheimer’s, Parkinson’s
  • Autoimmune: e.g. Multiple Sclerosis, SCID
  • Neurological: e.g. Fibromyalgia, Epilepsy

A Word from ITSHEMP

There’s no doubt that cannabinoids such as CBD and THC appear to hold a plethora of benefits for a wide range of ailments. However, please keep in mind that any treatment, even the natural ones, can have unwanted side effects. Self-treatment can put your health at risk so it is always advisable to involve your healthcare professional in your decisions. There are no clear guidelines regarding the legality of CBD in India. Therefore, it is important to do your research and thoroughly understand what is allowed and what is not. It can get overwhelming, in which case, the ITSHEMP team is here to help you.

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