OCTOBER 3, 2022

What Is The Endocannabinoid System?

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Scientists discovered the endocannabinoid system in the early 1990s, which is responsible for regulating mood, appetite, and memory throughout the body. 

It is activated by both cannabinoids created by the body – endocannabinoids – and those produced by plants – phytocannabinoids – which, as you might guess, is how it got its name (endo means “internal” and Phyto means “plant”).

Phytocannabinoids such as THC interacts with the body through cannabinoid receptors. A cannabinoid receptor is named after the main chemicals that activate it – cannabinoids. 

It was later discovered that the body produces very similar molecules that fit the same receptors. Endocannabinoids were named after them.

The endocannabinoid system (ECS) regulates memory, appetite, body temperature, the immune system, sleep, pain, and female reproductive functions. 

ECS regulates these functions to maintain body balance or homeostasis. A master regulator of homeostasis, it has even been called.

Endocannabinoids: how do they work?

To understand what the ECS is, it is helpful to imagine the process.

Let us take pain as an example. 

Imagine a woman named Emma jogging with her dog in the park. She trips over a rock and twists her ankle. The impact of hitting the ground immediately causes Emma to feel pain.  

However, after a fall, immediate pain is no longer necessary, so the central nervous system (CNS) slows down and stops the pain signals. 

Endocannabinoids, primarily anandamide and 2-AG, are produced by these enzymes.

There are two primary endocannabinoids in the body: Anandamide and 2-AG (2-Arachidonoylglycerol).

The anandamide hormone

Anandamide is commonly known as the “bliss molecule” because it regulates mood, reward response, and emotion. 

Depression, anxiety, and schizophrenia are associated with low levels of anandamide. Prescription medications used to treat pain and depression may increase anandamide levels.

Arachidonoylglycerol (2-AG)

2-AG reduces inflammation and regulates other immune functions, according to research. 

As with anandamide, 2-AG regulates mood, emotion, and pain perception, as well as memory, reproductive health, and sleep cycle regulation.

Endocannabinoids act as lipid signals, activating specific cellular receptors – like a key that unlocks certain types of locks. 

Cells throughout the body contain receptors that act as “locks.”.

As Emma experienced pain relief from her sprained ankle, enzymes produce endocannabinoids to promote appropriate inflammation at the injury site. The body produces endocannabinoids on demand, uses them, and then rapidly breaks them down in seconds. 


Cannabis interacts with the ECS, which is present throughout the body, even though we do not know exactly how it works. 

In the brain, the ECS plays an active role in conditions such as Parkinson’s disease, Alzheimer’s disease, chronic pain, stress, epilepsy, and autism spectrum disorders.

Unlocking the potential of the endocannabinoid system can improve the quality of life for many people

Cannabis can help people suffering from conditions such as Crohn’s disease and ulcerative colitis because cannabinoid receptors are abundant in the immune system. There are also receptors on skin cells, where cannabis can interact with dermatological conditions such as psoriasis. They are present in the lungs, where cannabis can interact with pulmonary diseases. 

The main reason cannabis is effective for so many conditions is that it interacts with a system that is present throughout the body. 

Two types of cannabinoid receptors exist cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2).

Receptors for CB1

The brain and spinal cord have the highest concentrations of CB1 receptors in the body. In the hypothalamus, CB1 receptors regulate metabolism, while in the amygdala, they regulate emotional responses. In addition, CB1 receptors are abundant in most nerve endings, where they control pain signals.

Receptors for CB2

There are CB2 receptors throughout the body, but they are most concentrated in peripheral tissues that are involved in immune function. Because the body often increases the availability of this receptor in injured tissues, the CB2 receptor may play a role in regulating the immune response to diseases. Inflammation is reduced when CB2 receptors are activated.

What functions does the endocannabinoid system regulate?

Endocannabinoids play a major role in maintaining homeostasis in the body, according to scientists. Today, we know that the ECS affects and regulates several body functions, systems, and conditions:

The endocannabinoid system helps to keep the body healthy 

The memory and learning process

Cognitive, memory and learning processes are controlled by cannabinoid receptors. Both cognitive processes and emotional behavior are controlled by CB1 receptors, which are highly concentrated in brain regions associated with cognition and memory. This function of the ECS is related to THC’s short-term memory effects.

Regulation of appetite

Researchers recognized decades ago that food intake is controlled by a complex process involving neurological, behavioral, and endocrine functions. 

Research suggests that modulating cannabinoid receptors is essential for regulating food intake and metabolizing macronutrients and fat. Additionally, modulating endocannabinoid signalling may help treat obesity and eating disorders. ECS plays an important role in the appetite of anyone who has ever experienced insatiable munchies.

Regulating body temperature

In response to changes in the external environment, the sympathetic nervous system adjusts heart rate and vasoconstriction. Furthermore, the body sometimes deliberately raises its core temperature to combat infection, with the endocannabinoid system playing a role. A common side effect of cannabis use is feeling cold due to THC’s ability to reduce body temperature.

The function of the immune system

Endocannabinoids can inhibit or stimulate the immune system by interacting with CB2 receptors. Researchers have hypothesized that modulating endocannabinoids could serve as a novel therapeutic approach for the treatment of inflammation and autoimmune diseases. They are in the early stages of investigating the role of the ECS in treating asthma, multiple sclerosis, osteoarthritis, and cancer. One reason THC is useful in treating serious autoimmune conditions like HIV/AIDS may be its ability to activate CB2 receptors on immune cells.

Processes of female reproduction

CB1 receptors are thought to modulate a wide range of complex activities in the hypothalamus, pituitary gland, and ovarian axis through their interactions with the ECS. 

Cannabis (as opposed to endocannabinoids) can disrupt the female reproductive system by reducing oestrogen and progesterone levels, but proper endocannabinoid system function is necessary for reproduction.

The sleep cycle and sleep quality

Circadian rhythms regulate sleep cycles, which are influenced by light and darkness. Activation of CB1 receptors in the ECS induces sleep in laboratory settings, according to research. People report using cannabis for sleep, so the importance of ECS in sleep should come as no surprise.

Perception of pain

One of the systems responsible for regulating pain is the ECS. From peripheral nerve endings to the brain and the central nervous system, endocannabinoids and their receptors are found in pain circuits of the nervous system. One of the most reported uses of medical cannabis in the US is pain management. Some early research suggests that cannabis may help patients reduce their need for opioids.

Autonomic processes

Numerous essential functions within the body are regulated by the autonomic nervous system. The sympathetic and parasympathetic branches make up this system. Sympathetic nerves control the “flight or fight” response, while parasympathetic nerves control the “rest and digest” response. The autonomic nervous system regulates functions and processes such as heart rate, digestion, thermoregulation, respiration, pupil dilation, and blood pressure.

All of this is known to us, but how? A genetically modified mouse lacking CB1 receptors was used to study the potential roles of the ECS. The researchers noticed issues with learning and memory, reward and addiction, pain, neuroinflammation and degeneration, metabolism and food intake, bone mass, and more – leading to the discovery that CB1 receptors regulate these functions. As with CB1, researchers learned that CB2 receptors play a role in several conditions, including autoimmune inflammatory diseases, chronic pain, alcohol addiction, and stress responses. 

Cannabis and the ECS: a research project

Cannabis and the ECS are relatively new research topics. Bill Devane, Lumir Hanus, and Raphael Mechoulam discovered the first endocannabinoid (anandamide) in Israel only four years after discovering the first cannabinoid receptor (CB1).

In addition, cannabis was illegal for decades, making it inaccessible as a treatment. Therefore, most of the early evidence of its medical uses came from anecdotal evidence from people who were technically breaking the law. The research process on this plant is extremely cumbersome, requiring special approval from multiple government agencies.

Cannabis is not all the same

Cannabis plants contain hundreds of different types of molecules. With thousands of cannabis strains or chemovars, each with its unique chemical profile, combinations and ratios are endless.

Scientists and researchers are examining different combinations of compounds and receptors to fully understand the full potential of the ECS.  

Most pharmaceutical medications contain only one or a few active ingredients. 

Researchers face a challenge when trying to understand how cannabis interacts with the ECS. To fully understand how cannabis works, scientists must examine thousands of different combinations of compounds and receptors instead of studying the effects of one compound on one receptor. 

Scientists and doctors don’t yet know which strains of cannabis are best suited to treating specific medical conditions. Cannabis patients often need to go through a lot of trial and error before they find a strain that works for them. 

Cannabis and ECS research: broadening horizons

Scientists are working hard to find anomalies in the expression of the ECS in patients with different conditions to understand if and how cannabis can benefit them.

Research in the field of cannabis therapeutics, led by Dr. Ethan Russo, suggests that patients suffering from fibromyalgia, migraines, IBS, autism spectrum disorder, multiple sclerosis, diabetic neuropathy, PTSD, recurrent miscarriages, and bipolar disorder may have dysregulated endocannabinoids. 

Researchers are still having difficulty matching cannabis chemovars – or even individual cannabinoids – to specific illnesses and patients who might benefit from them.

Globally, regulations that once hindered cannabinoid research are being loosened, which is good news for the cannabis industry. University and company researchers are carrying out a dizzying number of studies to better understand the ECS and how it interacts with cannabinoids. These studies include those produced by our bodies and those derived from cannabis.

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