Endocannabinoid System Receptors and the Potential Role of Cannabinoids
The endocannabinoid system (ECS) is a neuromodulatory network that spreads throughout the human body and participates in the development of the central nervous system (CNS) as well as plays a significant role in several cognitive and physiological processes.1 The ECS system consists of three components: endocannabinoids, endocannabinoid receptors, and enzymes.
Endocannabinoids (lipid-based neurotransmitters) refer to cannabinoids made in the body and can also be referred to as endogenous cannabinoids. Exogenous cannabinoids refer to cannabinoids that come from outside the body, while phytocannabinoids specifically refer to cannabinoids that originate from plants. The two most well-studied endocannabinoids (ECs) are the arachidonic acid derivatives, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), and have been found in all tissues, organs, and bodily fluids thus far investigated.2
Figure 1: There are three types of cannabinoids; endocannabinoids, phytocannabinoids, and synthetic exogenous. All these cannabinoids can bind to and activate the endocannabinoid receptors and regulate different processes in the body.3
In the ECS, there are different enzymes responsible for the synthesis and the degradation of endocannabinoids. Endocannabinoids are not stored in the body like other neurotransmitters and therefore are produced on demand. This process is extremely efficient, which makes it difficult to measure how many endocannabinoids are active in a person’s body at a given time.4
ECS receptors are proteins found on the surface of cells throughout the body. They are responsible for receiving and conducting the signals initiated by endocannabinoids. The number of ECS receptors outnumbers most other receptors in our bodies. Current research indicates that endocannabinoids in circulation come from multiple organs and tissues, including the brain, muscle, adipose tissue, and circulating cells.2
The effect that an endocannabinoid causes depends on where the receptor is located as well as which endocannabinoid binds to the receptor.
The two primary types of ECS receptors are:
- Cannabinoid receptor type 1 (CB1): CB1 receptors are mostly found in the central nervous system (CNS), specifically in the brain regions involved in memory, cognition, motor control, pain perception, and appetite regulation.5
- Cannabinoid receptor type 2 (CB2): CB2 receptors are mainly found in immune cells, the gastrointestinal system, and peripheral tissues. They are involved in modulating immune responses and inflammation.6
Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) or synthetic/exogenous cannabinoids can also influence the ECS.7 There have been more than 100 phytocannabinoids discovered in the cannabis plant as well as from other plants.3 When consumed, these exogenous cannabinoids interact with the ECS receptors, mimicking the effects of ECs. This has led to a large interest in using CBD as a therapeutic agent.1
ECs are made by the ECS enzymes as needed from membrane phospholipids and then diffused throughout cellular membranes. Once released from the postsynaptic neuron, the ECs bind to CB1 receptors found on the presynaptic membrane which then sends a signal to carry out a specific action. This is known as reverse signalling. The ECs are then removed from the synaptic junction after activating the CB1 receptor through cellular transport and then broken down by different enzymes that form part of the ECS.7
It is also important to mention that retrograde signalling is just one mechanism of action seen in the ECS. Other mechanisms of action include modulation and or activation of different channels in the body.1
Figure 2: A diagram showing the reverse signalling pathway of the ECS and how it reacts to cortisol in the body when someone is experiencing acute stress.4
Clinical endocannabinoid deficiency (ECD) theory suggests that ECS dysfunction, as a result of low endocannabinoid levels in the body, can contribute to the development of specific conditions.4 The reverse signalling process provides a mechanism for inhibitory feedback to control the release of neurotransmitters in the brain. Since the components of the ECS system are distributed throughout the body and as the ECS-signalling pathways play a pathophysiological role in many diseases, there are encouraging opportunities to develop new therapeutic drugs. It has also provided a strong rationale for investigating phytocannabinoids as therapeutic targets for the following conditions:5
- Autoimmune Diseases
- Cancer
- Cardiovascular Disease
- Stroke
- Alzheimer’s Disease (AD)
- Huntington’s disease (HD)
- Parkinson’s Disease
- Mood and anxiety disorders
- Pain management
- Epilepsy
- Inflammation
So, what is the take-home message?
The ECS plays a significant role in various cognitive and physiological processes and is controlled by endocannabinoids made by the human body. It can also be influenced by exogenous cannabinoids from cannabis plants, such as THC and CBD. The interaction of cannabinoids with ECS receptors shows promise for potential therapeutic applications in conditions like inflammation, pain, neurological disorders, and autoimmune diseases. However, further research is needed to fully understand the mechanisms and potential of cannabinoid-based therapies for these conditions.
M2Bio Sciences
M2Bio Sciences is a bioceutical company focused on alternative plant-based cannabinoids and mental health therapeutic research. M2Bio Science’s mission is to advance botanical-based medicine to the forefront by deploying best-practice science and medicine, clinical research, and emerging technologies. As one of a handful of companies in the world, M2Bio Sciences is actively researching the CBD compound to discover novel indications for different medical conditions.
The company has two consumer-facing brands, Medspresso™ and Liviana™. These brands offer a range of premium CBD-infused foods and beverages. M2Bio Sciences focuses on producing and sourcing the highest-quality ingredients available in the market, from pharmaceutical-grade CBD extract to premium coffees and extra virgin olive oil. All our products are ethically and sustainably produced in South Africa.
References
- Lu HC, Mackie K. 2020. Review of the Endocannabinoid System. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging,6(6). Available here.
- Hillard CJ. 2017. Circulating Endocannabinoids: From whence do they come and where are they going? Neuropsychopharmacology, 43(1):155–72. Available here.
- Kilaru A, Chapman Kent D. 2020. The endocannabinoid system. Essays in Biochemistry, 10;64 (3): 485–499. Available here.
- The Endocannabinoid System Explained [Internet]. www.youtube.com. [cited 2023 Aug 15]. Available from here.
- Lowe H, Toyang N, Steele B, et al. 2021.The Endocannabinoid System: A potential target for the treatment of various diseases. International Journal of Molecular Sciences, 22(17):9472. Available here.
- Battista N, Di Tommaso M, Bari M, et al. 2012. The endocannabinoid system: an overview. Frontiers in Behavioral Neuroscience, 6. Available here.
- Basavarajappa BS, Shivakumar M, Joshi V, et al. 2017. Endocannabinoid system in neurodegenerative disorders. Journal of Neurochemistry, 142(5):624–48. Available here.
- Cannabidiol and the Endocannabinoid System: A Brief Tutorial [Internet]. www.youtube.com [cited 2023 Aug 1]. Available from here.
- Luz-Veiga M, Azevedo-Silva J, Fernandes JC. 2023. Beyond pain relief: A review on cannabidiol potential in medical therapies. Pharmaceuticals, 20;16(2):155. Available here.
- Watt G, Karl T. 2017. In vivo evidence for therapeutic properties of Cannabidiol (CBD) for Alzheimer’s Disease. Frontiers in Pharmacology, 3;8. Available here.
