The endocannabinoid system
Endocannabinoid system (ECS)
Creating equilibrium in the body's internal environment.
The endocannabinoid system (ECS) is a complex network of receptors and molecules in our body that regulate various physiological processes. This discovery has sparked great interest among doctors and patients alike, as it has the potential to revolutionise the treatment of a wide range of medical conditions. This article will explore ECS in-depth and examine its importance for doctors and patients.
What is the endocannabinoid system?
The ECS is a complex system made up of three main components:
Endocannabinoids
Receptors
Enzymes
Present in all vertebrates and existence for around 600 million years, the system is widely distributed throughout the body, including the brain, organs, connective tissue, glands and immune cells[1]. It involves diverse processes such as appetite, blood pressure, blood flow to the brain, digestion, nausea, the immune system, inflammation, memory, mood, movement, pain, reproduction and stress [2]. Its complexity is reflected in its role as a "conductor" of the body's biochemical communication system, working to maintain homeostasis or internal equilibrium.
Functions and importance of the ECS
The endocannabinoid system represents a complex and fascinating area of research, acting as a meta-system with significant influence on various biological processes. The impact of cannabinoids is wide-ranging, but their common goal is consistent: to maintain homeostasis, or equilibrium [1], in the body's internal environment.
Usually, cell communication occurs through one-way communication, where one cell sends signals to the next cell via transmitter substances. The endocannabinoid system differs by using retrograde signalling. In other words, the endogenous cannabinoids run against the usual communication pathway [1]. When a cell emits excessive transmitter substances, endogenous cannabinoids are produced and sent back to dampen the signal.
The cannabinoids monitor various cellular "conversations" and provide feedback on a wide range of communications throughout the body. The system's main job is to fine-tune the communication between cells to ensure that there is not too much or too little activity. This applies to pain regulation, for example, where the system responds to excessive pain signals by dampening them with internal cannabinoids [3].
The discovery: A journey from the scientist's bag to human health
The story of the discovery of the endocannabinoid system begins in the early 1960s, with young chemist Raphael Mechoulam from the Weizmann Institute of Science on a bus from Tel Aviv to Rehovot. With 5 kilos of Lebanese hashish in his bag, confiscated from smugglers, Mechoulam begins his journey to uncover the chemical structures of cannabis[4]. Despite cannabis' historic medical reputation, research into its effects was still at a standstill. Mechoulam and the police chief broke some laws, but his reliability saved the project and continued his pioneering work[4]. Mechoulam was later recognised as "The Godfather of Cannabis Research" for identifying the chemical structures of THC and CBD, the active compounds in cannabis. Since then, over 100 active compounds have been found in the plant, collectively known as cannabinoids, but research has mainly centred on THC and CBD.
This "break with the law" was a groundbreaking event for cannabis research, as it made it easier for scientists to study THC and CBD synthetically without resorting to the controversial plant. In the late 1980s, the CB1 and CB2 receptors that these substances affect were identified. CB1 receptors are primarily in the brain and central nervous system, while CB2 receptors are found in other parts of the body, particularly in cells related to the immune system. In the 1990s, the body's own cannabinoids were discovered to bind to these receptors.
The endocannabinoid system is named after the cannabis plant: "Using a plant that has been around for thousands of years, we discovered a new physiological system that is hugely important... we would never have got there if we hadn't studied the plant." Rafael Mechoulam 2007 [4]. Mechoulam's research has since led to an explosion of publications related to cannabinoids. As such, it is now one of the most active research fields in neuropharmacology. The system is not fully understood, but its importance is undeniable.
Medical treatment options
ECS has been shown to play a role in the treatment of a wide range of medical conditions, including chronic pain, inflammatory diseases such as Crohn's disease and rheumatoid arthritis, neurological disorders such as epilepsy and multiple sclerosis, mental disorders such as anxiety and depression, and even cancer.
In addition to the main cannabinoids, THC and CBD, it has also been suggested that other compounds from the plants - such as the minor cannabinoids, terpenes and flavonoids - could have beneficial therapeutic effects and potentially influence the impact of each other when combined. This is referred to as the 'entourage effect'[5]. However, the mechanism of action of all the smaller secondary compounds in the plant is poorly studied, and more research is needed to clarify this topic truly.
After years of research into ECS, it has been discovered that the system works differently in people with Huntington's disease, chronic migraine, multiple sclerosis, PTSD, depression, schizophrenia, Parkinson's disease and fibromyalgia. Furthermore, there are indications that disturbances in the function of the endocannabinoid system play a significant role in substance dependence [6,7]. The fact that functional disturbances in the endocannabinoid system have been detected in such a broad spectrum of disorders is possibly because the endocannabinoid system has been working overtime to suppress an imbalance caused by the disorder.
With the increased understanding of ECS, several treatment options have emerged that aim to target this system[8]. Medicinal cannabis and cannabinoid-based drugs have been used to relieve symptoms and improve the quality of life for many patients. However, more research is still needed to understand ECS and develop more effective and safe treatments fully.
References
B. E. Alger, “Getting high on the endocannabinoid system.,” Cerebrum, vol. 2013, no. November, p. 14, 2013.
R. Mechoulam, “The Cannabinoids: Looking back and ahead,” CannMED conference 2016. Boston http://www.medicinalgenomics.com/wp-content/uploads/2016/05/mechoulam-CannMed2016.pdf, 2016
Zogopoulos, P., Vasileiou, I., Patsouris, E., & Theocharis, S. E. (2013). The role of endocannabinoids in pain modulation. Fundamental & clinical pharmacology, 27(1), 64-80.
R. Mechoulam, “Conversation with Raphael Mechoulam.,” Addiction, vol. 102, no. 6, pp. 887–893, 2007.
Russo, E. B. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology vol. 163 1344–1364 (2011).
M. W. Manseau and D. C. Goff, “Cannabinoids and schizophrenia: risks and therapeutic potential,” Neurotherapeutics, vol. 12, no. 4, pp. 816–824, 2015.
Parsons, L. H., & Hurd, Y. L. (2015). Endocannabinoid signaling in reward and addiction. Nature reviews. Neuroscience, 16(10), 579.
P. Pacher and G. Kunos, “Modulating the endocannabinoid system in human health and disease - Successes and failures,” FEBS J., vol. 280, no. 9, pp. 1918–1943, 2013.