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.
A BRIEF HISTORY OF THE ENDOCANNABINOID
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.
UNDERSTANDING THE ENDOCANNABINOID SYSTEM
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.