Exploring the Endocannabinoid System: What Every Clinician Should Know

The endocannabinoid system (ECS) plays a crucial role in how the human body functions, regulating important physiological systems such as pain, mood, temperature and immune response. Yet despite its important role, it is still not widely taught in medical schools. 

As interest in CBPMs continues to grow, understanding the ECS has never been more important for clinicians seeking to make evidence-informed decisions in practice. 

The ECS was discovered in the early 1990s by Israeli scientist Raphael Mechoulam during his research into the effects of the cannabis plant on the brain and body.

What he found was a system built into all animals with nervous and immune systems, which appeared to regulate a host of different functions in the body and brain, from pain and inflammation to body temperature and mood.

There are three major components of the Endocannabinoid System: Endocannabinoids, regulatory enzymes and receptors.

The key elements of the ECS that affect people’s health are the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), as well as the relative abundance and state of cannabinoid receptors, CB1 and CB2.

CB1 and CB2 receptors are G protein-coupled receptors produced in the body as a result of human evolution, Dr Monica Taing, a registered pharmacist and clinical cannabis consultant explained previously.

CB1 receptors are ubiquitous throughout the body and are predominantly found in the central nervous system,  with a high density in certain areas of the brain, whereas CB2 receptors are mainly limited to the periphery, including the immune system. 

Endocannabinoids act as partial agonists at CB1 and CB2 receptors. Activation of these receptors by anandamide and 2-AG has the potential to modulate anxiety/ stress, inflammation, pain perception, and neuropathic pain, among other processes.

Taing also explained how Delta-9-tetrahydrocannabinol (THC) mimics the effects of anandamide and 2-AG on CB1 and CB2 receptors, while CBD has multimodal activity at CB1 and CB2 receptors as well as at receptors beyond the ECS.

Over two decades, leading cannabis scientist, Dr Ethan Russo, has built on Mechoulam’s early work. 

In 2016, he put forward the theory of endocannabinoid deficiency as a cause of certain health conditions, particularly treatment-resistant syndromes like fibromyalgia, IBS and migraine.

Dr Russo hypothesised that in some conditions, there are deficiencies in the ECS that cause the system to be underactive, or to not produce enough of the endocannabinoids needed to regulate certain functions in the body and/or brain.

He found that if a patient supplemented their ECS with molecules that emulated the chemicals that transmit information from one nerve or one cell to another – known as phytocannabinoids – then this can help rebalance the ECS and, as a result, improve their symptoms.

Dr Elisabeth Philipps, a neuroscientist specialising in the ECS, previously told Cannabis Health: “It is still quite controversial in some ways, because the ECS is not widely understood, but in terms of fibromyalgia, IBS, migraine, what they call the treatment-resistant syndromes, I think an endocannabinoid deficiency is contributing.

“What we don’t know at the moment is specifically why there’s a deficiency in any of the systems – the ECS included. But what we do know is that by using cannabinoids, it is going to support areas like anxiety, sleep, and pain. For conditions like fibromyalgia, supporting the ECS function is going to be very much part of the picture of providing wellness.”

But despite the significance of the ECS in many health systems and the extensive research being carried out, its exclusion from medical education persists around the world, leaving a huge gap in understanding among professionals.

One study, published in October 2024, surveyed 610 nurses and nursing students in Portugal. It found that while 79.6% of nurses and 84.3% of students appreciated the therapeutic benefits of medical cannabis, 71.7% of nurses and 79.5% of students had never heard of the ECS.

Meanwhile, according to Dr Stefan Broselid, molecular pharmacologist, one of the most utilised and widely cited textbooks in medical education, Guyton and Hall Textbook of Medical Physiology, has omitted the ECS for over 30 years, including in the most recent 2020 edition. 

Speaking to Business of Cannabis, Broselid, who founded ECS Education, said: “If medical professionals aren’t being taught about the ECS in medical school, and currently, they’re not, they’re missing a crucial part of how the human body works. Without that knowledge, how can we expect them to deliver truly optimal care? It’s simply not possible.

“We have this expanding mountain of evidence, but it remains disconnected from the training that healthcare professionals receive.”

Continue this conversation at Cannabis Health Symposium on Tuesday 25 November, where Dr Rowan Thomspon will deliver a session dedicated to Exploring the Endocannabinoid System.

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