How does CBD work?

Before you understand how CBD works you must understand what the endocannabinoid system is! Read below 

What is the Endocannabinoid system?

The Endocannabinoid system (ECS) is not the new trend looking to profit from unwilling consumers. In fact, it was discovered almost 27 years ago. Despite its unearthing being almost 3 decades ago it has only been recently that many researchers and institutions have heavily investigated the role it plays in physiological and psychological responses in human and animal bodies.

The Endocannabinoid system is a regulator of homeostasis within the body. Homeostasis, put simply, is when the body is in perfect balance.1 The Endocannabinoid system is found in nearly every part of the body to encourage a state of homeostasis. To help you understand picture this. During your first night on vacation at a 5-star hotel you wake up in the middle of the night jetlagged, exhausted and bursting to go to the toilet. You leap out of bed and run towards the bathroom when BANG you fracture your toe on the side of your suitcase. Your body automatically responds to this stress through the lymphatic system and increases blood flow and white blood cells to the area which will cause inflammation. Following this the ECS initiates a homeostatic response by slowly reducing the original inflammatory response of the lymphatic system through a combination of endocannabinoids, endocannabinoid receptors and endocannabinoids enzymes which we will discuss in the next section.2

What is the Endocannabinoid system comprised of? 

The ECS is understood to be composed of 3 main components; endocannabinoids, cannabinoid receptors and enzymes.3 Endocannabinoids are fat based molecules that bind to cannabinoid receptors. Scientists have identified the molecules ADA (anandamide) and 2- AG (2- arachidonoyl glycerol) to be the most abundant endocannabinoids within the body.4  Upon requirement these molecules are released outside the cell.

Once released from the cell endocannabinoid receptors bind to free endocannabinoids (such as AEA and 2-AG) to initiate a response. For example, reducing inflammation following fracturing your toe when you were running to the bathroom on holiday. Within the ECS there are two main receptors; CB1 and CB2. The CB1 receptors are rich in the central nervous system (CNS) which is composed of the brain where they are particularly abundant and spinal cord. However, CB2 receptors are expressed at lower levels in the CNS and are more abundant within the immune system.5

The last part of the ECS is the endocannabinoid enzymes which are responsible for destroying endocannabinoids once they have completed their function. The endocannabinoid ADA is acted upon by the enzyme FAAH (Fatty acid amide hydrolase) and the 2-AG endocannabinoid is acted upon by the MAGL (monoacylglycerol lipase).6  Enzymes are protein molecules in cells which speed up chemical reactions and can be used over and over again.7 Enzymes are often described as locks as they are very specific to which keys (molecules) can be used upon them.  Whereas molecules such as endocannabinoids are described as keys as they must be specific to a lock (enzyme) in order to use it despite other molecules having similar shapes and without causing an effect. 

So why supplement CBD?

CBD molecules are able to block the effect of the endocannabinoid enzymes by binding to their active site which prevents endocannabinoids from being broken down.8-11 This is of particular benefit as endocannabinoids only have a half-life of less than five minutes and by slowing the breakdown process the availability of endocannabinoids acting within the body will be prolonged.12, 13 The use of CBD and therefore increased volume of endocannabinoids within the body has been shown to have multitude of potential health benefits such as; Pain & inflammation reduction, reduction in anxiety & depression, treatment of many skin conditions and many others.

References

  1. Cristino L, Becker T, Di Marzo V. Endocannabinoids and energy homeostasis: An update. BioFactors. 2014;40(4):389-397. doi:10.1002/biof.1168
  1. Sallaberry C, Astern L. The Endocannabinoid System, Our Universal Regulator. J Young Investig. 2018;34(6):48-55. 
  1. Barrie N, Manolios N. The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease. Eur J Rheumatol. 2017;4(3):210-218. doi:10.5152/eurjrheum.2017.17025

 

  1. Coccaro E, Hill M, Robinson L, Lee R. Circulating endocannabinoids and affect regulation in human subjects. Psychoneuroendocrinology. 2018;92:66-71. doi:10.1016/j.psyneuen.2018.03.009
  1. González-Mariscal I, Egan J. Endocannabinoids in the Islets of Langerhans: the ugly, the bad, and the good facts. American Journal of Physiology-Endocrinology and Metabolism. 2018;315(2):E174-E179. doi:10.1152/ajpendo.00338.2017
  1. Kendall D, Yudowski G. Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Front Cell Neurosci. 2017;10(294):833. doi:10.3390/ijms19030833
  1. Di Marzo V, Piscitelli F. The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics. 2015;12(4):692-698. doi:10.1007/s13311-015-0374-6
  1. De Petrocellis L, Ligresti A, Moriello A et al. Effects of cannabinoids and cannabinoid-enrichedCannabisextracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479-1494. doi:10.1111/j.1476-5381.2010.01166.x
  1. Deutsch D. A Personal Retrospective: Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the Fatty Acid Binding Proteins (FABPs). Front Pharmacol. 2016;7. doi:10.3389/fphar.2016.00370 
  1. Fogaça M, Campos A, Coelho L, Duman R, Guimarães F. The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling. Neuropharmacology. 2018;135:22-33. doi:10.1016/j.neuropharm.2018.03.001
  1. Hindocha C, Freeman T, Schafer G et al. Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. Addict Biol. 2019;25(3):1-18. doi:10.1111/adb.12762

 

  1. Ahn K, McKinney M, Cravatt B. ChemInform Abstract: Enzymatic Pathways that Regulate Endocannabinoid Signaling in the Nervous System. Chem Rev. 2008;108(5):1687–1707. doi:10.1002/chin.200835269

 

  1. Fine P, Rosenfeld M. The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Med J. 2013;4(4). doi:10.5041/rmmj.10129