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The endocannabinoid system (ECS) is a complex network of receptors, ligands, and enzymes that modulates various physiological processes such as pain, inflammation, mood, appetite, metabolism, and neuroprotection in the human body. The ECS was discovered in the early 1990s, when researchers identified the first endogenous cannabinoid (endocannabinoid) ligand, anandamide, and its receptor, CB1. Since then, at least four additional endocannabinoids have been discovered, one additional classical cannabinoid receptor, CB2, along with several enzymes involved in the synthesis and degradation of endocannabinoids. Several additional G protein-coupled receptors and multiple other voltage-gated ion channels have all been linked together into what we now commonly call the endocannabinoid system.
The ECS is a biological system that regulates many physiological and cognitive processes. The ECS is widely distributed throughout the body and interacts with other systems such as the nervous system, the immune system, the endocrine system, and the cardiovascular system. The ECS plays a key role in maintaining homeostasis and regulating various physiological responses to internal and external stimuli. The ECS is also involved in the pathophysiology of various diseases such as obesity, diabetes, neurodegenerative disorders, inflammatory disorders, psychiatric disorders, and cancer.
The table below shows some of the discoveries in physiology, the year of their discoveries, and their inclusion in the popular textbook “Guyton and Hall Textbook of Medical Physiology”.
| Discovery | Year | Inclusion in “Guyton and Hall: Textbook in Medical Physiology“ |
| Cellular circadian clock | 1994 | 2020 (14th edition) |
| Ghrelin | 1999 | 2000 (10th edition) |
| Toll-like receptor | 1997 | 2011 (12th edition) |
| Adiponectin | 1995 | 2006 (11th edition) |
| Melanocortins | 1980s | 2006 (11th edition) |
| Leptin | 1994 | 2000 (10th edition) |
| Nitric Oxide (NO) | 1987 | 1996 (9th edition) |
| Endorphins | 1975 | 1986 (7th edition) |
| Interleukin-1 | 1979 | 1986 (7th edition) |
| Somatostatin | 1973 | 1976 (5th edition) |
| Prostaglandins | 1971 | 1976 (5th edition) |
| Endocannabinoids | 1992 | 2016 (13th edition) *1 single mention |
| Endocannabinoid system | 1992 | not mentioned |
| 2-AG | 1995 | not mentioned |
| Anandamide | 1992 | not mentioned |
| CB2 receptor | 1993 | not mentioned |
| CB1 receptor | 1988 | not mentioned |
| FAAH | 1993 | Not mentioned |
Admittedly, the table is far from exhaustive, but it reveals some interesting patterns and gaps in the coverage of physiological discoveries in the textbook. For example, some discoveries were included very quickly after their publication, such as ghrelin, leptin, and nitric oxide. These discoveries were related to various topics, including innate immunity, metabolic syndrome, pain, inflammation, stress, appetite, and skin pigmentation, among others.
Undoubtedly, the most striking feature of the table is the complete absence of any mention of the ECS and its components. The ECS is a biological system composed of endogenous lipid-based neurotransmitters that bind to cannabinoid receptors in the central and peripheral nervous system. The ECS is involved in regulating many physiological and cognitive processes, such as pain, mood, memory, appetite, inflammation, and immune responses. It also happens to constitute the main pharmacological targets of the active compounds in cannabis, such as THC and CBD, but this has virtually nothing to do with its role and importance in human physiology.
Considering the critical role of the ECS in human health and disease, it is concerning that it has not been included in the ‘Guyton and Hall Textbook of Medical Physiology’ one of the most well-respected and used educational textbooks in medical physiology throughout medical schools across the world. It is tempting to correlate this omission of information to the current lack of understanding and acceptance of the system among the vast majority of medical professionals and educators, or a bias or stigma associated with cannabis research and its implications for medicine. Whatever the reason, the endocannabinoid system deserves more attention and recognition in physiology education. The physiology of the endocannabinoid system has nothing to do with cannabis and should not be allowed to be seen as controversial. The ECS is biology.
In a national survey conducted in 2017, medical school curriculum deans from 101 accredited American medical schools in the US reported that close to 90% of their residents and fellows do not feel at all prepared to prescribe medical cannabis and 85% report that they have received no education at all about the ECS or medical cannabis (Evanoff et al. 2017).
This table thus essentially reflects what is currently being taught in medical schools. Most doctors are not trained in the ECS and consequently have inadequate knowledge about the potential therapeutic uses of medical cannabis, contributing to the general low willingness to prescribe medical cannabis among doctors. Without an understanding of the ECS, it is difficult (read impossible) to fully comprehend the potential therapeutic uses of medical cannabis.
To address this gap in knowledge, medical schools should be highly encouraged to incorporate the ECS and its importance in homeostasis, health, and well-being into their human physiology courses.
“If it is the unfortunate nomenclature-based connotation to a misunderstood medical plant that is to blame, why not change the name of the endocannabinoid system to better reflect its main functional role rather than its etymological history? After all, if endocannabinoids had been discovered prior to phytocannabinoids, the ECS quite likely would have been known for its main function, perhaps as the homeostatic system? We shouldn’t have to rename it, but I can’t stop thinking about what would happen.”
Stefan Broselid, Ph.D.
Editor-In-Chief, Aurea Care Science Medical Journal
Evanoff AB, Quan T, Dufault C, Awad M, Bierut LJ. Physicians-in-training are not prepared to prescribe medical marijuana. Drug Alcohol Depend. 2017;180:151-155. doi:10.1016/j.drugalcdep.2017.08.010