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While many healthcare professionals are familiar with well-established physiological systems such as the sympathetic nervous system, which governs the body’s fight-or-flight response, fewer are aware of the more recently identified endocannabinoid system (ECS).1
The ECS has been increasingly recognised for its role in a range of regulatory functions, including pain modulation, immune response, stress and emotional regulation, appetite, body weight, and the control of nausea and vomiting.2
Yet, the ECS is not traditionally covered in medical education as highlighted by the Chief Scientific Officer of the Australian National Institute of Complementary Medicine: “I gave a talk at a hospital in Queensland late last year where I asked everyone in attendance—some 130 nurses, doctors, et cetera—whether they had had any training in the endocannabinoid system during their undergraduate training, and not one hand was raised.”3
Why isn’t the ECS taught in medical school?
The ECS is relatively new in the context of medical science. The primary cannabinoid receptors—CB1 and CB2—were only identified in 1988 and 1993, respectively.4
Similarly, the two most well-characterised endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were discovered in 1992 and 1995.4 This recency has contributed to its omission from traditional medical curricula, which can take years to evolve.
Cannabis, which interacts with the ECS,5 has a long history of medical use, dating back over 5,000 years.6 However, by the mid-20th century, it was no longer viewed through a medical lens but instead reclassified as a prohibited substance under the United Nation’s Single Convention on Narcotic Drugs.6 This shift in legislation didn’t just criminalise its use—it also severely limited research.6 With tight restrictions on access to cannabis for scientific purposes, progress on understanding its potential therapeutic benefits, including its interaction with the ECS, stalled for decades.
So what exactly is the ECS — and why it matters
The ECS is a cell-signaling system composed of three primary components:
Endocannabinoids—such as AEA and 2-AG—are lipid-based messengers naturally produced by the body that activate cannabinoid receptors.5Cannabinoid receptors—CB1 and CB2—are primarily located in the central nervous system and the peripheral immune system, respectively, though both are also found in other tissues throughout the body.5
Enzymes—fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)—are responsible for breaking down endocannabinoids.5
Endocannabinoids are released on demand by the body in response to physiological stimuli.7 Such stimuli may include: stress, obesity, food presentation, exercise, inflammation and tissue injury.2
The figure below outlines various stimuli reported to influence endocannabinoid levels and their observed effects from clinical studies:
In neurons, endocannabinoids are released in response to stimuli (such as those mentioned above) and exert their effects through a process called retrograde signalling.12 They are synthesised in the postsynaptic neuron and travel backward across the synapse to bind to receptors on the presynaptic terminal, where they inhibit further neurotransmitter release.12Emerging research suggests that deficient endocannabinoid signalling, collectively referred to as clinical endocannabinoid deficiency syndromes, may be involved in the pathogenesis of some diseases, including migraine, irritable bowel syndrome, depression, multiple sclerosis and Parkinson’s disease.13 This has led to growing interest in strategies to modulate levels of AEA and 2-AG, including targeting the enzymes that degrade them.13
Pain and inflammation
A study by Ramsden et al. offers intriguing insights into the relationship between diet, endocannabinoid tone, and headache severity.14 In participants with chronic headaches, increasing omega-3 intake while reducing omega-6 fats led to lower circulating levels of 2-AG.14 Interestingly, this shift was accompanied by a reduction in headache hours, hinting at the ECS as a potential therapeutic target in managing chronic headaches.14
Stress and anxiety
Research into the ECS and psychological trauma has revealed a complex picture.
Hill et al. found that individuals with post-traumatic stress disorder (PTSD) following the World Trade Center attack had low circulating levels of 2-AG compared to healthy controls.15 In contrast, Hauer et al. found the opposite trend in war refugees with PTSD, observing elevated levels of 2-AG compared to controls.16
These differing results suggest that the ECS may respond to psychological trauma in distinct ways depending on the context and intensity of the experience.16 While short-term ECS activation might serve as a protective mechanism during acute stress, prolonged or overwhelming trauma could lead to dysregulation—either depletion or overactivation—of this system.16
Looking ahead
Although historically overlooked in medical education,3 the endocannabinoid system is now recognised as one of the key regulators of physiological balance—with roles spanning pain, inflammation, stress, mood, appetite, and immune function.2 As the clinical relevance of endocannabinoid signalling continues to be uncovered, research is rapidly advancing into ECS-targeted therapies—offering novel options for managing complex and chronic conditions, particularly amid growing patient interest in cannabis-based treatments.1,6,7
This evolving understanding carries practical implications for clinical care. While some patients may benefit from cannabis-based treatments, others may experience side effects or find them unsuitable.17 A deeper understanding of the ECS may allow healthcare professionals to identify alternative or adjunctive strategies, and support patient-centred decision-making.3,18,19
As with all areas of clinical science, ongoing research, cautious interpretation of emerging data, and patient-centred dialogue will be key to integrating ECS knowledge into thoughtful, responsible practice.
Learn more about the ECS and its clinical implications with this fundamental module or our flagship accredited Medical Cannabis Fundamentals courses for doctors, nurses and pharmacists.
While many healthcare professionals are familiar with well-established physiological systems such as the sympathetic nervous system, which governs the body’s fight-or-flight response, fewer are aware of the more recently identified endocannabinoid system (ECS).1
The ECS has been increasingly recognised for its role in a range of regulatory functions, including pain modulation, immune response, stress and emotional regulation, appetite, body weight, and the control of nausea and vomiting.2
Yet, the ECS is not traditionally covered in medical education as highlighted by the Chief Scientific Officer of the Australian National Institute of Complementary Medicine: “I gave a talk at a hospital in Queensland late last year where I asked everyone in attendance—some 130 nurses, doctors, et cetera—whether they had had any training in the endocannabinoid system during their undergraduate training, and not one hand was raised.”3
Why isn’t the ECS taught in medical school?
The ECS is relatively new in the context of medical science. The primary cannabinoid receptors—CB1 and CB2—were only identified in 1988 and 1993, respectively.4
Similarly, the two most well-characterised endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were discovered in 1992 and 1995.4 This recency has contributed to its omission from traditional medical curricula, which can take years to evolve.
Cannabis, which interacts with the ECS,5 has a long history of medical use, dating back over 5,000 years.6 However, by the mid-20th century, it was no longer viewed through a medical lens but instead reclassified as a prohibited substance under the United Nation’s Single Convention on Narcotic Drugs.6 This shift in legislation didn’t just criminalise its use—it also severely limited research.6 With tight restrictions on access to cannabis for scientific purposes, progress on understanding its potential therapeutic benefits, including its interaction with the ECS, stalled for decades.
So what exactly is the ECS — and why it matters
The ECS is a cell-signaling system composed of three primary components:
Endocannabinoids—such as AEA and 2-AG—are lipid-based messengers naturally produced by the body that activate cannabinoid receptors.5
Cannabinoid receptors—CB1 and CB2—are primarily located in the central nervous system and the peripheral immune system, respectively, though both are also found in other tissues throughout the body.5
Enzymes—fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)—are responsible for breaking down endocannabinoids.5
Endocannabinoids are released on demand by the body in response to physiological stimuli.7 Such stimuli may include: stress, obesity, food presentation, exercise, inflammation and tissue injury.2
The figure below outlines various stimuli reported to influence endocannabinoid levels and their observed effects from clinical studies:
In neurons, endocannabinoids are released in response to stimuli (such as those mentioned above) and exert their effects through a process called retrograde signalling.12 They are synthesised in the postsynaptic neuron and travel backward across the synapse to bind to receptors on the presynaptic terminal, where they inhibit further neurotransmitter release.12
Emerging research suggests that deficient endocannabinoid signalling, collectively referred to as clinical endocannabinoid deficiency syndromes, may be involved in the pathogenesis of some diseases, including migraine, irritable bowel syndrome, depression, multiple sclerosis and Parkinson’s disease.13 This has led to growing interest in strategies to modulate levels of AEA and 2-AG, including targeting the enzymes that degrade them.13
Pain and inflammation
A study by Ramsden et al. offers intriguing insights into the relationship between diet, endocannabinoid tone, and headache severity.14 In participants with chronic headaches, increasing omega-3 intake while reducing omega-6 fats led to lower circulating levels of 2-AG.14 Interestingly, this shift was accompanied by a reduction in headache hours, hinting at the ECS as a potential therapeutic target in managing chronic headaches.14
Stress and anxiety
Research into the ECS and psychological trauma has revealed a complex picture.
Hill et al. found that individuals with post-traumatic stress disorder (PTSD) following the World Trade Center attack had low circulating levels of 2-AG compared to healthy controls.15 In contrast, Hauer et al. found the opposite trend in war refugees with PTSD, observing elevated levels of 2-AG compared to controls.16
These differing results suggest that the ECS may respond to psychological trauma in distinct ways depending on the context and intensity of the experience.16 While short-term ECS activation might serve as a protective mechanism during acute stress, prolonged or overwhelming trauma could lead to dysregulation—either depletion or overactivation—of this system.16
Looking ahead
Although historically overlooked in medical education,3 the endocannabinoid system is now recognised as one of the key regulators of physiological balance—with roles spanning pain, inflammation, stress, mood, appetite, and immune function.2 As the clinical relevance of endocannabinoid signalling continues to be uncovered, research is rapidly advancing into ECS-targeted therapies—offering novel options for managing complex and chronic conditions, particularly amid growing patient interest in cannabis-based treatments.1,6,7
This evolving understanding carries practical implications for clinical care. While some patients may benefit from cannabis-based treatments, others may experience side effects or find them unsuitable.17 A deeper understanding of the ECS may allow healthcare professionals to identify alternative or adjunctive strategies, and support patient-centred decision-making.3,18,19
As with all areas of clinical science, ongoing research, cautious interpretation of emerging data, and patient-centred dialogue will be key to integrating ECS knowledge into thoughtful, responsible practice.
Learn more about the ECS and its clinical implications with this fundamental module or our flagship accredited Medical Cannabis Fundamentals courses for doctors, nurses and pharmacists.