Endocannabinoids known to date
Endocannabinoids are cannabinoids we produce inside our bodies for functionalities we are just really starting to understand and build on. These endocannabinoids activate or bind to our endocannabinoid receptors in a system known as the Endocannabinoid System. I am going to touch on 6 endocannabinoids that have been identified in research science to date and their history and functions in our bodies.
The first two endocannabinoids discovered were in the late 1980’s and early 1990’s. The first one discovered and isolated was Anandamide (N-arachidonylethanolamine) and in its discovery we noticed it mimicked the psychotropic effects of plant-derived cannabinoids only after scientists realized it activated CB receptors in the body. Shortly after that, the second endocannabinoid discovered was 2-Arachidonoylglycerol (2-AG), an endogenous ligand of the cannabinoid receptors (CB1 and CB2). This led to the discovery of a few other endogenous agonists of CB receptors that were characterized and were collectively called “endocannabinoids”. Anandamide and 2-AG are the most commonly known cannabinoids but there are a few others that aren’t so popular but have led to more discoveries of more cannabinoid receptors other than CB1 and CB2.
2-Arachidonyl glyceryl ether (2-AGE, Noladin Ether) is a potent, and little known endocannabinoid that acts as a full agonist on the CB2 receptors. It binds to the CB1 receptor which causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice.
Virodhamine (O-arachidonoyl ethanolamine; O-AEA) is a signaling endocannabinoid that is derived from arachidonic acid. It is also made up of ethanolamine jointed by an ester linkage, which is opposite of the endocannabinoid Anandamide. It acts as an antagonist to the CB1 receptor and an agonist to the CB2 receptors. It also modulates the activity of the candidate cannabinoid receptor GPR55.
Palmitoylethanolamide (PEA) although PEA lacks affinity to CB1 and CB2 receptors it does not however in G-coupled receptors GPR55 and GPR119. PEA is also known to target Peroxisome Proliferator Activated Receptors (PPAR) along with the endocannabinoid, Oleoylethanolamide. A unique endocannabinoid for sure, the presence of PEA has been known to enhance anandamide activity creating its own "entourage effect". PEA has been shown to have anti-inflammatory, neuroprotective, and anticonvulsant properties.
Oleoylethanolamide (OEA) similar to Palmitoylethanolamide, it is an endogenous agonist to the PPAR. OEA is also structured similarly to Anandamide but unlike anandamide it acts independently of the cannabinoid pathway, regulating PPAR activity to stimulate lipolysis. OEA is said to be produced by the small intestine and its biosynthesis is modulated by bile acids. OEA has demonstrated to bind to the cannabinoid receptor GPR119. OEA has been suggested to be the GPR119’s endogenous ligand.
What does all of this indicate?
We naturally produce molecular compounds, endocannabinoids, which help regulate our body by interacting with our built in receptors (some discovered and possibly some undiscovered). Because we are built to receive these compounds, it is no mistake that not only our bodies produce these important things but they have also been found in plants. Phytocannabinoids or plant-based cannabinoids are what has sparked interest in learning more about this ecosystem of compounds and receptor sites. The most commonly known phytocannabinoids are found in the cannabis sativa plant. The same cannabis sativa plant that has been outlawed and demonized for many years. Understanding all of this will get us one step closer to realizing the particular connection we have to the world and its plants. If we are connected with these plants that are found on this earth it has to make you question, what else could we be connected with and what else do we not know?