Understanding the endocannabinoid system

UnderstandingThe Endocannabinoid System

The endocannabinoid system (ECS) is arguably the most influential in the body of vertebrate animals, including you and your furry friends. It is an integral part of so many living organisms, yet surprisingly, its discovery is quite recent. 


In the mid-1980s Allyn Howlett was the first to uncover the presence of a cannabinoid receptor. Many had speculated before this about the presence of cannabinoid receptors in mammalians, some so sure there must be a ‘lock and key’ mechanism behind the effects of cannabis. Others were indignant there was no need to seek out potential cannabinoid receptors, this kind of attitude unsurprising given the stigma still attached to cannabis at the time.

As the early 1990s unveiled further structures of the ECS – the numerous endocannabinoids, receptors and enzymes – it began to become clear how important and widely distributed this system is.

Truly, it’s a wonder we didn’t know about it earlier! And that this fundamental system is still largely excluded from medical and veterinary training.

Fast forward to the present day and we are still learning more about the ECS and its vast influence over physiology. Moreover, comprehending the subtleties and differences in the ECS of our common pets is a frontier we are only beginning to explore.


The ECS is a complex system interdependent and interwoven with pretty much every other body system in the body. Cannabinoid research Professor Vincenzo Di Marzo summarises the ECS in 5 words, “relax, eat, sleep, forget, protect”.

It has dynamic relationships with the immune, digestive, cardiovascular and nervous systems, making the ECS consequential in everything from regulating blood pressure to appetite and so much more in between.


The ECS is a system with components much like the nervous system. Where the nervous system contains neurotransmitters, the ECS contains endocannabinoids that could be more likened to messengers. The two most well-researched endocannabinoids are anandamide and 2-archidonylglycerol (2-AG).

Anandamide was called such by the “grandfather of medical cannabis” Raphael Mechuloam and his colleagues William Devane and Lumír Hanuš in 1992. Named after the Sanskrit word for bliss or joy -ananda- anandamide levels have been observed to be altered in those with mood or psychiatric disorders.

A 2015 study assessed humans with a common genetic polymorphism that inhibits the breakdown of anandamide and mice who had been treated to have the same genetic modification. The results showed that in both mice and humans, higher levels of anandamide (due to reduced breakdown) resulted in improved fear processing and reduced anxiety behaviours.

From this, it seems that anandamide plays a role in improving the relationship between the amygdala, the part of the brain that receives fear and stress inputs, and the prefrontal cortex which responds with behaviours and emotions.

Essentially, by having this genetic change the brains connections and ability to assimilate fear-based inputs were increased resulting in overall happier and less anxious individuals.

The other key endocannabinoid 2-AG is thought to have reign over the brain and nervous system while anandamides’ influence is spread more systemically.

There are many other endocannabinoids such as PEA and NADA, many of these are in present in minuscule numbers, yet play key roles in pain, inflammation and immunity – making them super intriguing for treating conditions of chronic pain and autoimmune disorders.


Other important players in the ECS symphony are the enzymes that synthesize endocannabinoids and those that degrade them once they’ve completed their function.

Another difference between endocannabinoids and neurotransmitters is that the former are synthesized on demand. Where neurotransmitters are generally already patiently waiting in the presynaptic vesicles, the body creates endocannabinoids – moment by moment- as they are required.


Finally, there are the all-important receptors that are stimulated by endocannabinoids and medical cannabis treatments. The two main cannabinoid receptors are both G protein-coupled receptors, referred to as CB1 and CB2.

Both receptors are found dispersed throughout the body with different areas of density. CB1 receptors are abundant in the brain and nervous system and are primarily famous for their interaction with THC – facilitating the intoxicating effects of cannabis.

Beyond the euphoric effects, CB1 receptors also contribute to maintaining biological balance via processes in the nervous and endocrine systems. In modulating hormonal release, influencing serotonin, dopamine and regulatory pathways they have both a direct and indirect role in mood, sleep, stress and pain.

CB1 receptors are also found in the cardiovascular and digestive system. In the heart, CB1 receptors moderate dilation and contraction of vessels thereby maintaining blood pressure, in the gastrointestinal tract they have influence over appetite hormones, motility and secretions.

CB2 receptors do not modulate the euphoric or intoxicating effects of cannabis or endocannabinoids but have a strong presence in the immune and reproductive systems. They are key mediators in the regulation of inflammation, pain and digestion, while in the skeletal system they are believed to play a role in maintaining bone density.

Numerous other receptors play a part in this orchestra. For example, cannabidiol (CBD), which is the dominant cannabinoid used for treating pets, interacts with other receptors such as TRPV’s and PPAR’s, as well as indirectly influencing ECS processes.

It is the activation of these receptors that are thought to account for CBD’s positive benefits in neuroprotection, pain and inflammatory conditions.

The bliss endocannabinoid, anandamide, has been shown to interact with serotonin receptors resulting in improved mood and pain relief.

Different animals express varying levels of these receptors making them more or less susceptible to the effects of endocannabinoids and medical cannabis treatments.

In particular dogs and cats seem to have slightly different expressions of ECS components, making it incredibly important that medicinal cannabis prescriptions are administered by a trained veterinary doctor for the safety of the animals.

he endocannabinoid system in dogs


Although much research pertaining to the effects of cannabinoids on humans is translated from rodent models, dogs and humans do have very similar ECS structures.

One key difference in the ECS of dogs, compared to humans and other animals, is the higher expression of CB1 in certain parts of the brain such as the cerebellum and basal ganglia. This makes dogs more susceptible to the intoxicating effects of THC.

Early research showed us that high dosages of THC can result in adverse effects for dogs such as ataxia – affecting movement and coordination. In rare cases of accidental ingestion of high doses of THC, dogs may collapse though morbidity is uncommon.

So THC is generally not suitable for pets and may only be safe in very low doses for specific conditions under the guidance of vets with knowledge in cannabinoid prescribing.

CBD on the other hand holds huge promise for dogs in particular. Unlike THC, CBD doesn’t interact with the ECS in the same fashion, making it a much safer therapeutic option for our pets.


Cats by their nature can be mysterious and elusive creatures, unsurprising then that research into medical cannabis and the ECS of cats is also elusive! As in dogs and humans, the feline ECS plays a big role in digestion, the nervous and immune systems.

Although research regarding the ECS of cats is very limited there has been some investigation into cannabinoid receptors in our feline friends. We know there is a strong presence of CB1 receptors in the nervous system of cats and there is research around CB2 receptors in the skin, gastrointestinal and reproductive organs.

One recent investigation of cats with dermatitis showed that cannabinoid receptors were increased in areas of the skin showing irritation. This indicates a protective mechanism whereby symptoms may be alleviated through targeting the ECS with topical or oral cannabinoid treatments.


New research is coming to light regarding how changes in the ECS may be at the root of many common symptoms or conditions in pets and humans.

Studies of dogs with epilepsy have shown their spinal fluid to contain higher levels of endocannabinoids than healthy dogs. With heightened levels of endocannabinoids come increased neuronal excitability and dysregulation in the control of signals in the brain.

Fortunately, CBD oil has been shown to reduce the incidence and severity of seizures in dogs. When administered under the supervision of a vet, CBD oil may also benefit pets with osteoarthritis, anxiety and chronic pain.

The understanding of the endocannabinoid system and its broad actions is only just beginning to be exposed in humans, with research into pets not far behind.

Fortunately, due to grassroots efforts from devoted pet owners and curious researchers, we can anticipate much to be revealed in the coming years as to how to target the ECS in pets to improve their health and wellbeing.

CBD Vets Australia work with Australian vets to safely administer legally prescribed CBD to dogs and cats who are in pain or suffering from a chronic illness. Learn more about how to prescribe CBD here and email [email protected] with any questions.

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