The Endocannabinoid System Explained

Once upon a time, a little blond haired girl came across a house in the woods. The girl’s name was Goldilocks, and the house belongs to a family of three bears – Papa Bear, Mama Bear, and Baby Bear.

The fairytale, as you know, goes on to explain how Goldilocks tried various things in the house – porridge, chairs, beds – looking for those that suited her best. Items intended for Papa Bear were either too hot, too big, too heavy or too hard. Mama Bear’s things were either too cold or too soft. Baby Bear’s things were just right.

This classic Robert Southey fairytale perfectly illustrates homeostasis.

Homeostasis And Why It Is Important

Homeostasis is a word of Greek origin. Two words to be exact – homoios, which means “similar” and stasis, which means “standing still.” The word refers to the biological process of maintaining a relatively constant internal environment. Walter Cannon, an American physiologist, coined the term in 1930.

A balanced internal environment is vital for optimal survival. In Goldilocks simple world, Papa Bear’s porridge would have burned her, and his bed would have given all sorts of aches and pains so she had to keep searching to find what was right. In the complex system called the human body, when homeostasis fails, the resulting imbalances may lead to a state of disease.

Genetics, lifestyle, or environmental factors, or a combination of all three can disrupt homeostasis. The endocannabinoid system (ECS), a biological system, plays a vital role in maintaining balance within the body and is also involved in physiologic functions.

The Endocannabinoid System

The endocannabinoid system is found in all vertebrates, i.e., birds, fish, amphibians, reptiles, and mammals. If it were not for cannabis, the ECS would have gone undiscovered.

In an attempt to understand the plant’s effects, initial research in the 1930s focused on identifying its individual compounds. Israeli scientist Raphael Mechoulam isolated and identified cannabidiol (CBD) from Cannabis sativa in 1940. Tetrahydrocannabinol (THC) was identified in 1964.

It wasn’t until 1988, during an experiment on a rat, that the first cannabinoid receptor (CB1) was discovered. Discovery of a second cannabinoid receptor (CB2)  happened in 1993. Additional receptors may be at play in the ECS, but are as of yet, unidentified.

Various intracellular cardiovascular, nervous, and immune system functions are regulated by the ECS. Those functions include the following:

  • appetite
  • digestion
  • immune function
  • inflammation
  • mood
  • sleep
  • fertility, pregnancy, and reproductive systems
  • motor control
  • temperature regulation
  • memory
  • pain
  • pleasure/reward

Three Key Components of the Endocannabinoid System

Cannabinoid receptors, endocannabinoids, and metabolic enzymes are three of the ECSs key components.

Cannabinoid Receptors

To know when homeostasis is threatened, the body’s cells need a way of monitoring what’s going on in their external environment. Cannabinoid receptors, a class of cell membrane proteins, work as neurotransmitters, and perform this function. Their location on the cell’s surface makes the,m perfectly suited for this role.

Cannabinoid type 1 (CB1) and cannabinoid type 2 CB2) are the two predominant receptors. The former is found in the central nervous system (CNS), connective tissues, gonads, glands, and organs. CB1 receptors facilitate the regulation of pain, sensation, memory, sleep, mood, and appetite.

CB2 receptors are found in the immune system, gastrointestinal system, spleen, tonsils, thymus gland, and brain. When stimulated, this receptor triggers an anti-inflammatory response that reduces pain and minimizes the tissue damage.

endocannabinoid system


Endocannabinoids are lipids and ligands that the body naturally produces. These compounds are uncharacteristic neurotransmitters in that they calm the nervous system down rather than stimulate it.

Anandamide (N-arachidonylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids. Both these endogenous compounds are synthesized upon demand, and capable of binding to CB1 and CB2 receptors but do so in different ways. 2-AG is an agonist at CB1 and a full agonist at CB2, while AEA has low CB2 affinity.

AEA, also known as the “bliss molecule” or “the molecule of wonder,” is linked to feelings of wellbeing and happiness. 2-AG, found at higher concentrations in the brain, regulates food intake and energy metabolism and modulates anxiety and depressive behaviors.

Metabolic Enzymes

Cannabinoid molecules need to be activated and inhibited at appropriate times. Metabolic enzymes are responsible for their synthesis and degradation, and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are the two major ones. FAAH breaks down the endocannabinoids anandamide. MAGL breaks down 2-A.

Cannabinoids and the Endocannabinoid System

Cannabinoids are chemical compounds that act as the chemical messengers of the endocannabinoid system. These compounds either interact with cannabinoid receptors or with endocannabinoids to exert their effects.

There are three distinct classes of cannabinoids – Phytocannabinoids (plants), endocannabinoids (body), and synthetic (man-made) cannabinoids.


Cannabis is the first thing people think of when phytocannabinoids are mentioned. However, these exogenous compounds are also found in cloves, liverwort, black pepper, Echinacea, broccoli, ginseng, kava, Chinese rhododendron, and carrots among other plants.

Cannabinoids are grouped as either psychoactive or non-psychoactive and offer unique health benefits when consumed. The therapeutic actions of these compounds are brought about by direct or indirect action on cannabinoid receptors. Cannabinoids have agonistic (activate certain receptors) or antagonistic (deactivating receptors) properties.

In the marijuana plant, cannabinoids are found in the sticky resin produced by small glands called trichomes. Of the up to 113 different cannabinoids isolated from the cannabis plant, the two best-known and probably most researched cannabinoids are THC (Tetrahydrocannabinol) and CBD (Cannabidiol).


  • THC (Tetrahydrocannabinol) – THC is responsible for the intoxicating and euphoric high in cannabis and is produced by decarboxylation of THCA (Tetrahydrocannabinolic Acid). This compound is a partial agonist of cannabinoid receptor CB1, and relieves pain, stimulates appetite, reduces nausea, suppresses muscle spasms.


  • CBD (Cannabidiol) – CBD is a non-psychoactive compound(see this page for more). It is a partial agonist of cannabinoid receptor CB1. Its therapeutic effects include pain relief, inflammation reduction, appetite stimulation, nausea reduction, anxiety relief, psychosis relief, seizure/convulsion reduction, muscle spasm suppression, blood sugar management, nervous system degeneration prevention, psoriasis treatment, reduces risk of artery blockage, kills or slows bacterial growth, inhibits cancerous cell growth, promotes bone growth.

Other cannabinoids include:

  • CBGA (Cannabigerolic Acid) – Antibacterial (slows bacterial growth), anti-proliferative (inhibits cancer cell growth).
  • CBDA (Cannabidiolic Acid) – Inhibit cancerous cell growth and reduces inflammation.
  • CBCA (Cannabichromenate) – Anti-fungal and anti-inflammatory effects.
  • CBC (Cannabichromene) – Pain relief, inflammation reduction, bacteria growth inhibitor, bone growth promotion, cancer-cell growth inhibitor.
  • CBG (Cannabigerol) – Inhibits growth in tumorous or cancerous cells, pain relief, inflammation reduction, bacteria growth inhibition, treats fungal infection, promotes bone growth.
  • CBDV (Cannabidivarin) – Anticonvulsant effects
  • CBN (Cannabinol) – Pain relief, muscle spasm suppression, sleep aid.
  • THCA (Tetrahydrocannabinolic Acid) – Inflammation, seizure, and cancel cell growth reduction.
  • THCV (Tetrahydrocannabivarin) – Appetite suppression, seizure suppression, blood-sugar level reduction, bone growth promotion.

Endocannabinoid Deficiency Syndrome

The ECS helps the body maintain homeostasis. To do this, its three components – cannabinoid receptors, endocannabinoids, metabolic enzymes – must work in sync as well. This is referred to as the endocannabinoid tone. When your endocannabinoid tone is imbalanced (low endocannabinoids or receptor production), you may develop endocannabinoid deficiency syndrome (EDS).

Causes of EDS include chronic stress, poor diet, drugs, disease, and genetics. Researchers have linked ECS to the following conditions:

  • Fibromyalgia
  • Pain
  • Anorexia
  • Depression
  • Irritable Bowel Syndrome (IBS)
  • Migraines
  • Multiple Sclerosis (MS)
  • Post-Traumatic Stress Disorder (PTSD)
  • Neuropathy
  • Huntington’s
  • Parkinson’s
  • Motion Sickness
  • Autism

Restoring Endocannabinoid System Balance

  • Exercise – Physical exertion increases serum concentrations of endocannabinoids. You can increase anandamide production by spending an hour or more doing moderate-intensity exercise.
  • Fish oil – Endocannabinoids are products of dietary fats like omega-6 and omega-3 fatty acids. Adding foods rich in those nutrients like salmon, eggs, walnuts or tofu can boost endocannabinoid production
  • Detoxing – When cannabinoid receptors are over-activated, the brain decreases how many of them it makes available. This action imbalances the ECS. A period of detox can help resolve this.
  • Phytocannabinoids – CBD supplements and other cannabis products can boost the body’s natural production of endocannabinoids.
  • Sunlight – The ECS is influenced by circadian (sleep-wake cycle regulator) cycles. Getting 15 minutes of solar ultraviolet radiation raises levels of 2-AG.
  • Stress-Reducing Activities – Chronic stress can deplete the ECS by overstimulating cannabinoid receptors. Any stress-reducing activity like meditation, yoga, massage can enhance endocannabinoid functioning.
  • Orgasm – Orgasms from masturbation increase the circulating levels of endogenous cannabinoids AEA] and 2-AG.
  • Fasting – Endocannabinoid levels increase during fasting. A 24-hour fast can temporarily boost 2-AG levels and help restore balance to the ECS.


Fortunately for us, many modern CBD tinctures and capsules also have CBG, CBN, and CBC along with the regular cannabidiol that they contain.

This means that your endocannabinoid system will receive a wider array of compounds stimulating it when you take CBD oil.

The endocannabinoid system is an important biological modulatory system, and we have cannabis to thank for its discovery. The ECS is comprised of a complex system of cannabinoid receptors, endocannabinoids, and metabolic enzymes. Together these three components function as potent regulators of vital health functions like appetite, pain, digestion, reproduction, motor learning, stress, and memory among others.

To help maintain balance or homeostasis in the human body, cannabinoid receptors, endocannabinoids, and metabolic enzymes cannot be overactive or underactive. If this happens, the endocannabinoid tone becomes imbalanced and you may develop endocannabinoid deficiency syndrome (EDS). Taking supplemental cannabinoids from the cannabis plant as well as staying active and sticking to a proper diet can help prevent EDS.

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