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What Is The Endocannabinoid System? A Guide To ECS

Endocannabinoid

What Is The Endocannabinoid System?

Scientists have known that the brain had opiate receptors since the early 70s. 15 years later in a government-funded study, two St. Louis University School of Medicine researchers discovered that we had receptors in our brain that respond to cannabis.

For many young adults in the 70s and 80s, this wasn’t news.

The endogenous cannabinoid system, as it was originally called, was discovered in the mid-1990s during trials on THC—the substance in cannabis that makes you high. A research team led by Dr. Linda Matsuda discovered a complex network of cannabinoid receptors (CB-1). Her team were able to map the DNA of the receptor, and eventually clone it.

Later, a second cannabinoid receptor (CB-2) was found. This led to the question:

Why does the body create cannabinoid receptors unless we also produce cannabinoids to bind with them?

Our bodies produce serotonin to bind with serotonin receptors (5-HT receptors) to regulate mood. We produce dopamine to bind with dopamine receptors, in order to support our executive functions. If we produced cannabinoid receptors, somewhere within us we were producing cannabinoids.

Scientists’ assumptions were proven correct when anandamide was discovered. This was the first naturally-occurring, cannabinoid-like chemical discovered within the body to bind with receptors. In early tests, it was shown to modulate the central and peripheral nervous systems.

Although research into the ECS and its capabilities is still in its infancy, researchers and scientists have amassed a great deal of data to help us understand its complex, intricate processes.

What makes up the ECS?

Over the 25 years since Dr. Matsuda’s initial discovery of cannabinoid receptors and the human endocannabinoid system, researchers have studied the network of processes and working parts involved within our bodies.

In its simplest terms, the ECS is made up of three components.

  1. Endocannabinoids
  2. Cannabinoid receptors
  3. Enzymes

 Endocannabinoid system

  • Endocannabinoids

These fat-like molecules are produced by our bodies, and bind to the cannabinoid receptors to activate them. In addition to anandamide, researchers have identified 2-arachidonoylglyerol (2-AG) as another naturally occurring endocannabinoid. The difference between an endocannabinoid and a cannabinoid is that endocannabinoids are produced within the body on-demand. Cannabinoids, on the other hand, are introduced to the body—THC being the most commonly known.

  • Cannabinoid receptors

At this point in time we know of two receptors: CB-1 and CB-2.

CB-1 can be found in the brain and spinal cord. These receptors relate to our central nervous system.

CB-2 can be found in our peripheral nervous, immune, and digestive systems.

According to research, we may produce more cannabinoid receptors in the body than all other neuromodulatory receptors put together. As an example, anandamide—critical to the health of our central nervous system—has more receptors in the human brain than any neurotransmitter. There is some hypothesis that we may have a third cannabinoid receptor, although this remains scientifically unfounded. We’ll learn about cannabinoid receptors as we move through this article, but for now we’ll move on to the third component of the endocannabinoid system.

  • Enzymes

The last piece of the ECS puzzle is the metabolic enzyme. These enzymes are created to break down endocannabinoids once they’ve served their purpose. Fatty Acid Amide Hydrolase (FAAH) works to break down anandamide, while Monoacylglycerol lipase (MAGL)targets 2-AG. The ECS is different to hormonal and neurotransmission processes in that it acts quickly to release enzymes and stop the action of the endocannabinoid. Hormones and neurotransmitters can both remain active for longer, or be stored by the body.

So, let’s do a quick breakdown of the process. Your body is alerted to an issue. It activates the endocannabinoid system to deal with the issue. The ECS targets exactly what it has to do—for example, heal inflammation in your knee after you hurt it climbing the stairs. It works with precision, regulating the immune system without messing around with your digestion or cardiovascular system.

Once the mission is complete, enzymes are released within the body to stop the active endocannabinoids from going overboard. Problem solved.

What is the function of the ECS?

People wrongly assume that the term endocannabinoid somehow relates to cannabis. It doesn’t. To put this misconception to rest—breast milk contains endocannabinoids to stimulate growth, development, and digestive activity in newborn babies.

The primary function of the endocannabinoid system is balance.

Our body needs to maintain itself within strict parameters to function well. Blood sugar levels, body temperature, hormone levels, heart rate, hunger—there are multiple systems within the human body that need to be within a narrow range of conditions in order for our cells to do their jobs. These constant processes to maintain the right level of everything in our body are ultimately trying to achieve homeostasis—a stable balance between all our intertwined, interdependent systems. The endocannabinoid system’s job is to help maintain homeostasis.

Put more simply, Leafly call this the Goldilocks zone. The ECS is playing its role to make sure everything within your body is just right.

Your body activates the endocannabinoid system to correct your internal processes and get them back on track. If you’re overheating, your ECS prompts you to sweat in order to cool you down. If you stub your toe, your ECS works to reduce inflammation (but more on this in the next section).

Much like all the behind the scenes activity that keeps your smartphone running well so you can check social media and read articles in peace, your ECS is working around the clock—monitoring your internal functions and doing its best to make sure nothing crashes.

What parts of the human body does the ECS affect?

Experts have identified key areas in human health which are influenced in some way by the endocannabinoid system. These include functions such as:

  • Metabolism
  • Digestion
  • Liver function
  • Muscle formation
  • Bone growth
  • Bone recovery
  • Fertility and the reproductive system
  • Skin growth and healing
  • Nerve function
  • Digestive organ health
  • Cardiovascular system processes

Because the human body is made up of hundreds of interdependent processes which rely on each other for optimal performance—homeostasis—it is no wonder the ECS is tied up in all these areas.

What is Clinical Endocannabinoid Deficiency, and why does it matter?

Unfortunately, it is possible for a network as complex as the endocannabinoid system to run into problems.  So what happens when things go wrong for the ECS?

Some research suggests that Clinical Endocannabinoid Deficiency (CECD)—where low endocannabinoid levels are present within the body—can actually contribute to the progression of illness and disease. Similarly, ECS dysfunction has been linked to migraines, irritable bowel syndrome, and fibromyalgia.

ECS dysfunction, whether from low endocannabinoid levels or not, can cause confusion at a molecular level. Research has demonstrated that where dysfunction is present, the endocannabinoids can target inappropriate cells, deactivate ineffectively (or not at all) because metabolic enzymes fail to release, or release incorrectly.

Some scientists who subscribe to the Clinical Endocannabinoid Deficiency theory believe that by introducing cannabinoids from plants—like cannabis, for example—to our body, we can correct the dysfunction and rebalance our internal systems.

the central nervous system

ECS and the Central Nervous System

Although there are multiple areas impacted by the ECS, this article focuses mainly on the relationship between the endocannabinoid system and the central nervous system. We’ll explore that now.

The CB-2 receptor, which was discovered a few years after CB-1, relates primarily to the peripheral nervous and immune systems. CB-2 molecules have also been found in bone, reproductive tissue, and the reproductive organs.

In this section, we mainly focus on the first cannabinoid receptor—the CB-1. We already know the CB-1 receptors are located mainly in the brain and spinal cord, which is our ground control unit—the central nervous system.

CB-1 has been proven to be the most widely represented receptor protein in the brain. More so even than serotonin and dopamine receptors, and those are the ones most of us are familiar with.

The largest concentration of CB-1 receptors is found in the hippocampus, basal ganglia, and cerebellum. There is also a moderate number in the cerebral cortex, amygdala—the part associated with our emotions—and the hypothalamus. 

Now we can see how widespread this cannabinoid receptor is throughout our central nervous system. The next logical step for researchers was to explore the wide range of roles it plays there, ranging from anxiety and alcoholism, to Alzheimer's disease, Huntington's disease, and many forms of cancer.

Earlier we explored some of the areas linked to the endocannabinoid system. There are more than we can get into in this article, but the predominant areas that link the ECS with the central nervous system are below. Here, we break down the ways the endocannabinoid system interacts with these specific areas.

Cancers

In almost every conversation about the medical benefits of treating the endocannabinoid system, someone is likely to mention cancer. As you can expect, there are hundreds—possibly thousands—of medical and scientific studies linking the ECS to the anti-cancer war.

There is so much more to this research than we could cover in the scope of this article. Studies into the ECS—and specifically the cannabinoid receptors—tend to focus on specific cancer types, and there are more types of cancer than there are letters of the alphabet.

Here we will focus on some general findings in popular ECS research. We’ll also look at how these findings support—or don’t support—claims that the ECS is the key to eliminating cancers.

First up: how did the endocannabinoid system end up so firmly in the anti-cancer limelight?

The sheer number of palliative studies run on the ECS and it’s roles in fighting cancer are attention-grabbing. Rightly so. The endocannabinoid system plays a role in restricting the growth and spread of tumors, and the development of new tumors. It has also shown results in studies into the effect cannabinoid receptors have on skin cancer and U.V. rays.

In all these areas, clinical trials are still going on. These will likely carry on for decades to come.

Here’s what we do know. CB-1 and CB-2 receptors get together with other receptors within the body. The short name for this group of receptors is GPCRs—we’ll dig into these more soon. Scientists have discovered many of these groups—named complexes—within the body, in healthy cells and in cancerous cells. The complexes have unique properties that allow them to affect the cells they’re found it.

Still with us?

Basically, and in absolutely non-scientific terms, the complexes might help the ECS break down tumor cells.

The potential of these complexes—which are called heteromers—in anti-cancer treatment is being heavily explored, and comes with its own set of clinical and ethical setbacks, but early discoveries have been positive. In addition to what scientists have shared so far, there is the fact that our ECS is linked to every key area of cancer biology. Our ECS works with expert precision. When you look at these two statements together, it’s clear to see how the ECS may hold the key to targeted treatment of cancer cells.

In a study run by the Department of Biochemistry and Molecular Biology, led by Dr. M. Guzman in Madrid, artificially activating the CB-1 and CB-2 receptors led to a reduction in tumor growth. Other studies support this.

Vanderbilt University Medical Center conducted a study under Dr. D. Wang. In this study, the researchers reduced the number of CB-1 receptors in a trial specimen, and it led to accelerated tumor growth.

The University of Naples Federico II discovered that higher endocannabinoid levels reduced pre-cancerous lesions.

These are convincing arguments for the ECS as a focus for cancer research, right? As with all medical research, it’s not all good.

The Institute of Hematology at Erasmus University, Rotterdam, discovered that high levels of CB-2 receptors contributed to a higher risk of leukemia.

As we’ve discussed throughout this article, research into the ECS—and more specifically the role of the ECS in medical treatment—is still young. We are a long way from proving or disproving the efficacy of targeting our cannabinoid receptors in disease treatment.

Appetite and food intake

The effects cannabinoids have on appetite are well known. In street terms, we’re talking about ‘the munchies’. A healthy CB-1 receptor count, when bound with endocannabinoids or cannabinoids, has been proven to increase appetite in many instances. Studies have also shown communication between the cannabinoid receptors in the brain and our appetite regulating hormones—leptin, orexin, and ghrelin. So not only does the ECS boost appetite to normal levels, it can also regulate appetite as part of an anti-obesity treatment for overeaters.

Neurodegenerative diseases

Researchers in a recent study recommended therapeutic treatments that focus on ECS should be trialed in the treatment of brain illnesses—even in advanced cases like strokes and epilepsy.

Tests performed in patients with neurodegenerative diseases—diseases like Alzheimer’s, Parkinson’s, and Huntington’s—showed changes in how the CB-1 receptor is expressed. In simple terms, the receptors were faulty.

In Huntington’s disease, for example, a progressive loss of CB-1 is considered an early symptom of the illness. It shows before the onset of neurodegeneration in several cases. Delaying CB-1 loss in medical studies was shown to delay the onset of motor disorders and disease progression in Huntington’s patients.

Motor control

Studies into the endocannabinoid system and motor control are well documented across the internet. The areas of the brain which control motor function—the basal ganglia and cerebellum—are home to lots of the CB-1 receptors.

Introducing cannabinoids to the body has a direct effect on the CB-1 receptor, alleviating problems with our motor skills.

Treating the ECS has also shown positive results for symptoms of multiple sclerosis and muscle wastage. As with many areas related to the endocannabinoid system, more research is needed.

Inflammation

Inflammation is how our body responds when something is wrong. Infection causes inflammation. Physical damage results in bruises—a very visible type of inflammation. Do you know what causes it? It is your immune system sending cells and fluids to clean up the area and repair you. Sometimes the inflammation lasts longer than it’s meant to. When doctors talk about chronic inflammation—this is what they mean.

As Vice President for Research at a major university, Professor Nagarkatti oversees research into endocannabinoid regulation of immune responses. He suggests that stimulating the ECS could lead to more successful treatment of inflammatory diseases.

the human Endocannabinoid system

Pain management

This was one of the first medical concerns treated with cannabinoids. Studies have shown that cannabinoid use is successful for a wide range of pain types, from burns and chemical pain to inflammation, and many cancers. Chronic pain, especially, can be reduced with cannabinoids. The endocannabinoid system is involved in the regulation of inflammation, too.

Learning and memory

Many studies into the impact of ECS on cognitive functions involve the use of cannabis. In our research for this article, we found that the majority of studies did the following:

Introduced natural cannabinoids into the body to stimulate the CB-1 and CB-2 receptors—basically, they used some form of cannabis, and

Administered the enzyme FAAH to disrupt the receptors’ activity.

Results across several studies showed that introducing cannabinoids mildly improved information retention and mid-term memory, but had a negative impact on short-term memory and short-term problem solving.

Where ECS receptors may prove to have more impact is in our brain’s reaction to external influences. Recent studies indicate that activating the CB-1 receptors may affect how we perceive our environmental influences. The improved perception of our environment was directly linked to improved emotional and cognitive behavior.

In unscientific terms: when we feel better about our environment, we learn better.

Anxiety and depression

One study has already linked the endocannabinoid system and anxiety. The study, led by Dr. Sachin Patel and Professor James G. Blakemore, explored how the brain adapts to stress. It found that if the CB-1 receptors in our amygdala—remember, that’s the part of our brain that processes emotions—are blocked or faulty, anxiety levels go up.

Another study by Patel focused on 2-AG. If you want a reminder, 2-AG is one of the cannabinoids our body produces naturally. This study showed that lower than normal levels of 2-AG in mice created depressive and anxious behavior. In mice with an increased level of 2-AG, behavior was more stable and less indicative of anxiety.

Cannabinoid Receptors—What Are They?

We’ve already had an overview of the cannabinoid receptors. If you want—no, need—to dig deeper, the rest of this article is for you. We tell you more about what cannabinoid receptors are, why they are special, and what is cannabinoid receptors relationship with other receptors in the body. The section after the jump also breaks down where they are expressed in the body.

To recap, scientists have discovered two cannabinoid receptors in the human body—CB-1 and CB-2.

We know that scientists are speculating as to whether or not we have more cannabinoid receptors in our body.

We know that the first receptor discovered was by Dr. L.A. Matsuda in 1990, and named CB-1 (or CB1R). Through her team’s research into the effects of THC on the human brain, she concluded that this receptor was activated by cannabinoids.

The second receptor was discovered away from the central nervous system of the body, mainly within the immune system. Early tests showed that this receptor could potentially play a role in modulating the immune system. Its discovery marked the start of research into the non-psychotropic effects of cannabinoids, and it was named CB-2 (or CB2R).

What else do we need to know about cannabinoid receptors?

They belong to a biological group of G-protein coupled receptors—the GPCR we explored in the section on how the ECS interacts with cancers. This group plays a valuable role in communicating signals from outside the cells to various intracellular signaling molecules. Their chemical makeup is unique in the body of humans and animals.

In simple terms, GPCRs send updates around your body about the current state of affairs.

This family of receptors has had a profound effect on the medicines we use today, and modulates activity from our growth to our hormone levels, feelings, and pain tolerance. Another interesting fact—research shows that over a third of all pharmaceutical drugs on the market today work by binding to GPCRs.

Cannabinoid Receptors in the Body

We’ve clarified the basics of where our cannabinoid receptors are found. Generally speaking, CB-1 is produced in our central nervous system, and CB-2 is produced in the peripheral nervous system, immune system, and digestive system.

If you need the specifics, we have more.

Both CB-1 and CB-2 can be found outside these areas. Our lungs, skin, liver, lymph nodes and bones also benefit from the work of our endocannabinoid system. This means we must have cannabinoid receptors in those parts of our body. Cannabinoid receptors are also found in our reproductive system.

Conclusion

Experts agree that we still have a long way to go in understanding the complexities of the endocannabinoid system.

A study conducted by David B. Allen in 2013 showed that only 21 out of 157 surveyed medical schools in the U.S. included ECS study in their curriculum. None of the schools surveyed offered classes on the subject. Whether this lack of education for American doctors is detrimental to the future of ECS research and quality studies remains to be seen.

In the meantime, we can keep our brains busy by unpacking everything we know about the ECS right now.

Here’s what we learned today:

  • The history of the ECS
  • The three components that make up this system
  • What the ECS does
  • How it does it
  • What we know about receptors

The ECS is a vital molecular system that our bodies need to maintain internal balance. It is a tightly run ship that goes where it’s needed at any given point in our lives. If we can develop a deeper understanding of the endocannabinoid system and its processes, we will see if—as many hope—it unlocks the door to improvement in treatments of major medical conditions.

cannabinoid receptors