Endocannabinoid

ˌendō- kə-ˈna-bə-ˌnȯid | Noun

An organic compound produced by the body that binds to cannabinoid receptors. Anandamide and 2-arachidonoylglycerol (2-AG) are the two most prevalent cannabinoids made by the body. Endocannabinoids share a likeness to plant-produced cannabinoids called phytocannabinoids. Within the human endocannabinoid system, endocannabinoids are responsible for regulating the brain, endocrine, and immune systems and play an essential role in maintaining the body’s homeostasis, or internal regulatory balance.

 

“Maybe your illness is a result of endocannabinoid deficiency.”

 

“Your endocannabinoids help your body maintain balance.”

What Are Endocannabinoids?

Cannabinoids are a class of lipophilic molecules that interact with the body’s endocannabinoid system (ECS). The role of the endocannabinoid system is to help the body maintain functional balance through its three main components: “messenger” molecules that our bodies synthesize, the receptors these molecules bind to, and the enzymes that break them down. Endogenous cannabinoids, or endocannabinoids, are the body’s “messenger” molecules that trigger homeostatic reactions when they bind to cannabinoid receptors.

 

 

There are two main cannabinoid receptors: CB1 and CB2. CB1 receptors are primarily found in the central nervous system, where they regulate a wide variety of brain functions. CB2 receptors are mostly found on immune cells, which circulate throughout the body and brain via the bloodstream. They’re also found on neurons in a few select brain regions. CB2 receptors are involved in pain relief, anti-inflammation, and neuroprotection. The body’s most prominent endocannabinoids, namely anandamide and 2-AG, also activate TRPV proteins, which are responsible for the body’s sensations of heat and cold. The heat you experience from eating a chili pepper, for example, is a TRPV-mediated response. Although the CB and TRPV receptors are the major players in the ECS, there are at least three other receptors (GPR55, GPR18, and GPR119) that may eventually be considered cannabinoid receptors, once their functions are fully understood.

Endocannabinoids vs. Phytocannabinoids

Endocannabinoids are produced inside the body, as opposed to phytocannabinoids, which are produced outside the body — most commonly and abundantly in the cannabis plant. Because our bodies already use cannabinoid molecules to regulate many functions, we’re inherently endowed with many targets the cannabis plant can activate. Endocannabinoids and phytocannabinoids aren’t necessarily different on a structural level. They both activate the body’s ECS by binding to cannabinoid receptors found throughout the body, across several systems. Endocannabinoids activate a homeostatic effect, bringing the body to a balanced state of health. They are produced by our cells in an “on demand” fashion. Think of the ECS as an equalizer of sorts for your body, kind of like an air-traffic controller. Endocannabinoids send signals to your body to set it back to its equalizer preset, much like an air-traffic controller sends signals to pilots to ensure the planes in the surrounding space fly safely.  

 

Phytocannabinoids amplify individual signals that trigger responses related to everything from hunger and pain to hearing and spatial orientation. When a phytocannabinoid amplifies a hunger signal, for example, you get the munchies. Phytocannabinoids are also capable of producing intoxication through ECS modulation, which endocannabinoids alone cannot do.

How Are Endocannabinoids Produced?

Endocannabinoids move between different types of neurons in your body. This movement between neurons is how your body “communicates” messages about what needs to happen to control and balance a wide range of bodily functions.

 

There are two main types of neurons involved in this process: presynaptic neurons and postsynaptic neurons. When a postsynaptic neuron is activated, your body uses available fat cells (more properly called “lipid precursors”) to create an endocannabinoid, which then jumps from the activated postsynaptic neuron to a nearby presynaptic neuron, where it then attaches to a cannabinoid receptor.

 

According to Scholastic, this process is “backward” when compared to the functions of regular neurotransmitters, which move from presynaptic neurons to postsynaptic neurons. Interestingly, this backward flow of endocannabinoids means that they can influence how neurotransmitters behave before they activated. This is one of the features that appears to make the endocannabinoid system so powerful and versatile.

Are Endocannabinoids Stored in the Body?

No, your body does not store endocannabinoids. Instead, as explained in the scientific journal “Cerebrum,” endocannabinoids are produced when the right type of neuron is activated. At that point, your body quickly uses available lipids to produce an endocannabinoid, which then travels between neurons and attaches to an endocannabinoid receptor.

Known Endocannabinoids and their Mechanisms

Anandamide and 2-arachidonoylglycerol (2-AG), the body’s two most well-known endocannabinoid neurotransmitters, seek out both CB1 and CB2 receptors. They also activate TRPV and several other receptor proteins. 2-Arachidonyl glyceryl ether (2-AGE), commonly known as Noladin ether, also binds to both CB1 and CB2, as well as the TRPV protein channel TRPV1. N-arachidonoyl dopamine (NADA) acts primarily on the CB1 receptor, but also activates TRPV1.  O-arachidonoyl-ethanolamine (OAE) binds to both CB1 and CB2 receptors, but is only a partial agonist of CB1, meaning it’s potential to activate a response is limited compared with a full agonist. 

What Do Endocannabinoids Do?

Given its complexity, there is more than one endocannabinoid system function. In fact, this system is involved in numerous bodily functions and contributes to your body’s ability to maintain homeostasis. Every function in our bodies requires a specific balance of factors to perform at maximum capacity. When this balance is achieved, it’s called homeostasis. Endocannabinoids are the messenger molecules that are critically involved in this internal regulatory response. Pain, stress, appetite, energy metabolism, cardiovascular function, reward and motivation, reproduction, and sleep are just a few of the functions that endocannabinoids can target by activating cannabinoid receptors. 

Pain and Inflammation

Both anandamide and 2-AG play a role in modulating pain — both neuropathic and inflammatory — through CB1 and CB2 receptor pathways. They have been found in pain-modulating regions throughout the central nervous system, and may have a hand in modulating inflammatory pain through CB2 receptors. When administered exogenously to animals, these cannabinoids have exhibited pain-relieving potential similar to that of exogenous cannabinoids such as THC and CBD.   

Mood (Anxiety, Depression)

The endocannabinoid 2-AG may be heavily involved in controlling anxiety and depressive behaviors. A 2014 study on 2-AG levels in mice indicates that 2-AG deficiency could be a contributing cause of anxiety and mood disorders.

Stress

Endocannabinoids play an integral role in modulating stress responses. They’re even involved in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, the body’s central stress regulation system.

Appetite and Energy Metabolism (Obesity, Diabetes)

Several studies have shown that CB1-agonist endocannabinoids play a role in regulating appetite and hunger. CB1 receptor antagonists, (compounds that inhibit CB1 receptors, rather than activating them, have also been researched for its role in inhibiting appetite and reducing body weight.  

Sleep

Anandamide has been found to regulate sleep stability by activating CB1 Receptors. 2-AG may also have the ability to induce REM sleep through CB1 activation.    

Cardiovascular System

The ECS is spread prominently throughout the cardiovascular system. Under normal conditions, endocannabinoids have a minor role in cardiovascular regulation, but they also have the potential to intervene in instances of hypo- and hypertension.

Gastrointestinal System

Through CB1 and CB2 receptor activation, endocannabinoids can play a role in protecting the gastrointestinal tract from inflammation and other high gastric abnormalities.

Healthy Brain Function

The endocannabinoid system is heavily involved in regulating brain function. At different stages of learning and memory, endocannabinoids that activate CB1 receptors may be able to modulate stress and anxiety associated with emotional memory. Endocannabinoids can also have both neuroprotective and neurodegenerative effects. 2-AG contributes to brain homeostasis as both an anti-inflammatory and neuroprotectant. The role of the ECS in healthy brain function makes it an ample target for treating PTSD, addiction, schizophrenia, and neurodegenerative disease.

Healthy Cell Function

The ECS has been heavily implicated in fighting cancer and promoting healthy cell function. Studies have shown the ECS to have massive therapeutic potential in relation to cell proliferation and tumor growth when acted upon by exogenous cannabinoids. These findings also suggest that endocannabinoids play a role in the healthy function of kidney, liver, and bone cells.

Clinical Endocannabinoid Deficiency Syndrome (CECD)

Clinical endocannabinoid deficiency (CECD) was first proposed in 2001 as an explanation for the therapeutic properties of cannabis. The theory posits that several illnesses that have been successfully treated with plant-based cannabinoids are a result of a deficiency in the body’s endocannabinoids. Current research supports this theory, indicating that deficiency in the production of endocannabinoids is a viable explanation for migraine, fibromyalgia, irritable bowel, and other treatment-resistant syndromes. CECD may also play a role in anxiety and mood disorders. It’s also possible that CECD may be a reason more and more people are finding relief from different ailments after using CBD oil.

While much is still unknown about the endocannabinoid system, research is beginning to shine a light on just how integral endocannabinoids are when it comes to maintaining homeostasis.