Although it is arguably one of the most important systems within the human body, the endogenous cannabinoid, or endocannabinoid, system often gets overlooked in our education. In fact, many individuals may have never heard those words before despite this system being present in all vertebrates (UCLA Health)! That is why we will focus on this diverse and widespread system in this blog.
Interestingly, the endocannabinoid system was discovered by and named after the very plant that derives our patients’ medications (Alger, 2013). Exogenous cannabinoids produced by the plant, such as THC and CBD, are labeled as phytocannabinoids (Kinsey, 2020). In investigating where THC binds to within the human body, scientists discovered the first cannabinoid receptor, CB1. Researchers then believed there must be a compound naturally produced within the body that must bind to this receptor. This led to the discovery of anandamide, which will be described in the next paragraph.
Let’s start with a description of what scientists have mapped out so far as the endocannabinoid system. First, it is important to note that this is a retrograde system, in that its signaling molecules travel “backwards” across a synapse (post to pre-synapse) (Letscher, 2018). The signaling molecules, known as endogenous cannabinoids, or endocannabinoids, are lipids that are produced by the body and bind to cannabinoid receptors to activate them (Kilaru and Kent, 2020). These molecules consist of anandamide and 2-arachidonoylglycerol (2-AG) (Kinsey, 2020).
These molecules, as well as the phytocannabinoids produced by cannabis, bind to cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). CB1 receptors are the most widely expressed protein in the brain (Zou and Ujendra, 2018). They are expressed in neurons, astrocytes, oligodendrocytes, and microglia. The brain areas with the highest concentrations of these receptors are the olfactory bulb (role in odor perception), hippocampus (role in learning and memory), basal ganglia (role in voluntary motor movements, emotions, learning), and cerebellum (role in voluntary motor movements). In the peripheral nervous system, CB1 receptors are exhibited in the gastrointestinal tract, enteric nervous system, enteroendocrine cells, immune cells, and enterocytes. On the other hand, CB2 receptors are seen in macrophages in the spleen, immune cells, the brain, and peripheral tissues such as the cardiovascular and reproductive system and GI tract.
One enzyme that regulates the biosynthesis and breakdown of endocannabinoids includes fatty acid amide hydrolase (FAAH), which metabolizes anandamide. Another enzyme involves monoacylglycerol lipase (MAGL), which metabolizes 2-AG (Kinsey, 2020).
This system clearly plays a role in a wide variety of processes due to its receptors being present in many areas of the body (Letscher, 2018). The primary function of the endocannabinoid system is to maintain physiological homeostasis (Kilaru and Kent, 2020). It has also been shown to reduce systemic inflammation (Kinsey, 2020), and it is involved in pain, memory, mood, appetite, sleep, metabolism, immune function, and reproductive function (UCLA Health). Moreover, it is believed to play a role in liver function, bone remodeling and growth, stress, and cardiovascular functioning (Raypole, 2019). As you can see, endocannabinoids are one of the most widespread and versatile signaling molecules known.
Specifically, anandamide is believed to contain analgesic effects, dulling or removing physical pain and psychological discomfort. This is why it is believed that stimulation of the endocannabinoid system may be useful for treating PTSD, as it helps patients leave their traumatic life experiences in the past (Alger, 2013). 2-AG is the most prevalent endocannabinoid and it has a large role in anti-inflammatory effects (Letscher, 2018). It is also important to note that cannabinoids are quickly synthesized and broken down, leading to less long-term side effects.
The endocannabinoid system continues to be investigated by researchers, as there is still so much to be discovered. Hopefully, patients will feel more informed after reviewing this post with regards to the endocannabinoid system and how it interacts with cannabis medications. And if there are any remaining questions regarding this lesser known system, please feel free to reach out to us!
Citations:
Alger, Bradley E. “Getting High on the Endocannabinoid System.” Cerebrum : the Dana Forum on Brain Science, The Dana Foundation, 1 Nov. 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/.
Kilaru, Aruna, and Kent D. Chapman. “The Endocannabinoid System.” Portland Press, 10 July 2020, portlandpress.com/essaysbiochem/article-abstract/doi/10.1042/EBC20190086/225762/The-endocannabinoid-system?redirectedFrom=fulltext.
Kinsey, Steven. “What Is a Cannabinoid?” Kinsey Lab, 24 Jan. 2020, kinsey.lab.uconn.edu/what-is-a-cannabinoid/.
Letscher, Emily. “The Endocannabinoid System, Our Universal Regulator.” Journal of Young Investigators, Journal of Young Investigators, 1 June 2018, www.jyi.org/2018-june/2018/6/1/the-endocannabinoid-system-our-universal-regulator.
Raypole, Crystal. “Endocannabinoid System: A Simple Guide to How It Works.” Healthline, Healthline Media, 17 May 2019, www.healthline.com/health/endocannabinoid-system.
UCLA Health. “Human Endocannabinoid System.” Human Endocannabinoid System – UCLA Cannabis Research Initiative – Los Angeles, CA, www.uclahealth.org/cannabis/human-endocannabinoid-system.
Zou, Shenglong, and Ujendra Kumar. “Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System.” MDPI, Multidisciplinary Digital Publishing Institute, 13 Mar. 2018, www.mdpi.com/1422-0067/19/3/833/htm.