Endocannabinoid System Explained [with Infographic]
April 2, 2020
Once associated with drugs and breaking the law, cannabis is now leading scientists to new discoveries in health and the human body. Studies on the effects of marijuana have brought scientists to an understanding of the biological system known as the endocannabinoid system, which has been discovered to potentially play an important role in the regulation of our physiological and cognitive processes, including: 
- Mood
- Fertility
- Memory
- Sleep
- Appetite
- Metabolism
- Inflammation
- Bone Growth
- Stress
- Muscle Formation
What is the Endocannabinoid System?
The endocannabinoid system (ECS) is a natural cell-signaling system in our bodies made up of endocannabinoids, receptors, and enzymes that assist in the regulation of biological functions. Basically, the endocannabinoid system is activated when something in the body is not operating in the correct range.
What does “endocannabinoid” mean?
The term “cannabinoid” was first coined with the cannabis plant and is one of over 100+ naturally occurring compounds found in cannabis. “Endo” is short for “Endogenous”, which means that it originates from within an organism. The literal meaning of the word “endocannabinoid” is having cannabis-like compounds within the body. So, the same type of chemicals in cannabis are found inside our bodies? Yes! When extensive government-funded studies were conducted on the effects of THC in the early 90s, they discovered the same compounds of cannabis in the human body. Since then, the endocannabinoid system has been discovered in other animals including mammals, birds, fish, and amphibians. [2] The endocannabinoid system includes more than just the cannabinoids. It is made up of three parts:- Endocannabinoids – The signaling molecules within the body that are the same type of compounds found in hemp.
- Receptors – Chemical structures made of protein that receive and convert signals from endocannabinoids and cannabinoids.
- Enzymes – The substances that help synthesize and break down the endocannabinoids and cannabinoids.
How Does the Endocannabinoid System Work?
ECS is more than just a natural system in our bodies; it plays an essential role in the regulation of multiple functions and plays a critical role in maintaining homeostasis within living systems. When understanding the endocannabinoid system, it is critical to first understand how homeostasis works and why it plays such an important role within the body. What is homeostasis? Homeostasis is the state of stable equilibrium for internal, physical, and chemical conditions controlled by the human body. In order to understand this process, it is helpful to look at examples that we may experience in everyday life. For example, have you ever had the shivers when too cold or were sweating when you were hot? This is a great example of the body maintaining homeostasis. The body works to keep a stable and steady temperature of around 98.6 degrees Fahrenheit (37 degrees Celsius) and while it may only change by a few degrees, it makes a large difference in keeping your internal temperature at a desirable level. How about your stomach growling after an extended period without food? Once again, that is homeostasis in effect reminding your body to eat food for more energy. Homeostasis is also maintained in the body with the immune system, water levels, sugar levels, blood pressure, calcium levels, and many more important systems that need constant regulation. The endocannabinoid system works to keep homeostasis within the body and while it is critical to staying stable and healthy, it is not active 24/7. It is only activated when it is needed and called upon by the body. It also only impacts the living system that is out of homeostasis without changing other systems in the body. For example, if your blood pressure is too high or too low, ECS will be activated, telling the heart to pump more or less blood to place the blood pressure at a healthy level without changing the immune system or body temperature levels.Endocannabinoid Components Working Together
As mentioned, ECS is made up of the three core components- enzymes, receptors, and endocannabinoids. Here’s how it works.- A living system in the body falls outside of the healthy and optimal levels (out of homeostasis).
- The endocannabinoid system is activated to maintain the levels of the living system and brings it back to a stable equilibrium. It does this with the cannabinoid receptors which listen to the various systems within the body, should they fall outside a healthy level.
- After the endocannabinoids have brought the system back to a balanced state, enzymes in the ECS break them down to prevent them from going too far in the opposite direction and upsetting the balance. They act as the barrier to the endocannabinoids overcompensating to fix the issue.
Endocannabinoids & Cannabinoids
We already know that endocannabinoids are similar compounds to the ones found in cannabis but are instead formed inside the body. Let’s explore what we currently know about these cannabinoids.Cannabinoids found in the Cannabis Plant
There are over 100 cannabinoids in hemp but there are two that have gained lots of attention in recent years and are on the forefront of most research studies.- Tetrahydrocannabinoid (THC)
- Cannabidiol (CBD)
Cannabinoids found in the Endocannabinoid System
The cannabinoids discovered by research studies so far include:- Anandamide (AEA)
- 2-arachidonoylglyerol (2-AG)
Endocannabinoid Receptors
There are two main endocannabinoid receptors that have been discovered in the human body:- CB1 receptors – found in the central nervous system, which controls most functions of the mind and body.
- CB2 receptors – found primarily in the peripheral nervous system, which consists of the nerves and ganglia not found in the brain and spinal cord.
Enzymes in the ECS
The two main enzymes responsible for breaking down endocannabinoids after they have completed their task include:- Fatty acid amide hydrolase (FAAH) – responsible for breaking down the endocannabinoid anandamide (AEA)
- Monoacylglycerol (MAGL) – breaks down the endocannabinoid 2-AG
How Does Cannabis Affect the Endocannabinoid System?
We already know that cannabis affects the ECS, but how exactly does it work compared to the endocannabinoids found in our bodies? The chemical structure of the cannabinoid THC is similar to the endocannabinoid anandamide. Just like the endocannabinoid, THC can attach to the CB1 receptor in the brain when someone uses a cannabis product. While both cannabinoids are related, anandamide does not give a high, although, the endocannabinoid does have relaxing and sedative properties. In fact, the only reason that anandamide does not get a user high is because of the FAAH enzyme which breaks down the endocannabinoid before it can produce any psychoactive effects. While the FAAH enzyme works to break down the cannabinoids found within the body, it cannot break down THC. Therefore, THC can have a much stronger effect. That brings us to another plant-based cannabinoid found in cannabis that has been on the forefront of many research studies, known as cannabidiol, or CBD. Many research studies have been documented to support the potential therapeutic benefits of CBD for various conditions including:- Anxiety [3, 4, 5, 6, 7, 8, 9, 10, 11]
- Psychotic Symptoms [12]
- Inflammation [13]
- Sleep [14, 15, 16]
- Depression [17, 18]
- Arthritis [19, 20]
- Epilepsy [23, 24]
- Mood
- Inflammation
- Sleep
- Stress
- CBD has been reported to have therapeutic effects for multiple conditions in modern research studies.
- CBD is a cannabinoid (like the cannabinoids naturally found in our bodies) and has a connection with the CB1 and CB2 receptors in the endocannabinoid system.
Choosing a CBD Product that is Natural
At 43 CD Solutions, all our hemp is grown locally with natural farming practices and is included with organic carrier oils. We believe that when choosing to try CBD as part of a potential treatment for various conditions, it is important to choose a product that is natural and high-quality while being backed by third-party testing. As with any alternative medicine, we recommend asking your doctor if CBD is the right choice for you. If you have any additional questions about the endocannabinoid system and how cannabis works with your body, feel free to give us a call or email us with your questions. References:- Chye Y, Christensen E, Solowij N, Yücel M. The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder. Front Psychiatry. 2019;10:63. Published 2019 Feb 19. doi:10.3389/fpsyt.2019.00063
- Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147 Suppl 1(Suppl 1):S163–S171. doi:10.1038/sj.bjp.0706406
- Zuardi, A.W., Shirakawa, I., Finkelfarb, E. et al. Action of cannabidiol on the anxiety and other effects produced by δ9-THC in normal subjects. Psychopharmacology 76, 245–250 (1982). https://doi.org/10.1007/BF00432554
- Guimarães, F.S., Chiaretti, T.M., Graeff, F.G. et al. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology 100, 558–559 (1990). https://doi.org/10.1007/BF02244012
- Zuardi, A. W., Cosme, R. A., Graeff, F. G., & Guimarães, F. S. (1993). Effects of ipsapirone and cannabidiol on human experimental anxiety. Journal of Psychopharmacology, 7(1_suppl), 82–88.
- Crippa, J., Zuardi, A., Garrido, G. et al. Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow. Neuropsychopharmacol 29, 417–426 (2004). https://doi.org/10.1038/sj.npp.1300340
- Gomes, F.V., Resstel, L.B.M. & Guimarães, F.S. The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology 213, 465–473 (2011). https://doi.org/10.1007/s00213-010-2036-z
- Bergamaschi, M., Queiroz, R., Chagas, M. et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacol 36, 1219–1226 (2011). https://doi.org/10.1038/npp.2011.6
- Blessing, E.M., Steenkamp, M.M., Manzanares, J. et al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics 12, 825–836 (2015). https://doi.org/10.1007/s13311-015-0387-1
- Shannon S, Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J. 2016;20(4):16-005. doi:10.7812/TPP/16-005
- De Gregorio D, McLaughlin RJ, Posa L, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160(1):136–150. doi:10.1097/j.pain.0000000000001386
- Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2(3):e94. Published 2012 Mar 20. doi:10.1038/tp.2012.15
- Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. doi:10.4155/fmc.09.93
- Murillo-Rodríguez, E., Millán-Aldaco, D., Palomero-Rivero, M., Mechoulam, R., & Drucker-Colín, R. (2006). Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats. FEBS letters, 580(18), 4337-4345.
- Chagas, M.H.N., Eckeli, A.L., Zuardi, A.W., Pena‐Pereira, M.A., Sobreira‐Neto, M.A., Sobreira, E.T., Camilo, M.R., Bergamaschi, M.M., Schenck, C.H., Hallak, J.E.C., Tumas, V. and Crippa, J.A.S. (2014), Cannabidiol can improve complex sleep‐related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther, 39: 564-566. doi:10.1111/jcpt.12179
- Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18–041. doi:10.7812/TPP/18-041
- Shoval G, Shbiro L, Hershkovitz L, Hazut N, Zalsman G, Mechoulam R, Weller A: Prohedonic Effect of Cannabidiol in a Rat Model of Depression. Neuropsychobiology 2016;73:123-129. doi: 10.1159/000443890
- Liat Shbiro, Danielle Hen-Shoval, Noa Hazut, Kayla Rapps, Shira Dar, Gil Zalsman, Raphael Mechoulam, Aron Weller, Gal Shoval, Effects of cannabidiol in males and females in two different rat models of depression, Physiology & Behavior,Volume 201,2019, Pages 59-63,ISSN 0031-9384
- A. M. Malfait, R. Gallily, P. F. Sumariwalla, A. S. Malik, E. Andreakos, R. Mechoulam, M. Feldmann, The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis, Proceedings of the National Academy of Sciences Aug 2000, 97 (17) 9561-9566; DOI: 10.1073/pnas.160105897
- Hammell, D., Zhang, L., Ma, F., Abshire, S., McIlwrath, S., Stinchcomb, A. and Westlund, K. (2016), Transdermal cannabidiol reduces inflammation and pain‐related behaviours in a rat model of arthritis. Eur J Pain, 20: 936-948. doi:10.1002/ejp.818
- Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3):833. Published 2018 Mar 13. doi:10.3390/ijms19030833
- Manoela V. Fogaça, Alline C. Campos, Ludmila D. Coelho, Ronald S. Duman, Francisco S. Guimarães, The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling, Neuropharmacology, Volume 135, 2018, Pages 22-33, ISSN 0028-3908
- Michal Tzadok, Shimrit Uliel-Siboni, Ilan Linder, Uri Kramer, Orna Epstein, Shay Menascu, Andrea Nissenkorn, Omer Bar Yosef, Eli Hyman, Dorit Granot, Michael Dor, Tali Lerman-Sagie, Bruria Ben-Zeev, CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience, Seizure, Volume 35, 2016, Pages 41-44, ISSN 1059-1311
- Pamplona Fabricio A., da Silva Lorenzo Rolim, Coan Ana Carolina, Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis, Frontiers in Neurology, Volume 9, 2018, Pages 759, ISSN 1664-2295
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