More Than Meets the Eye!
It is not entirely fair that CB1 receptors and CB2 receptors get all the credit for the healing properties within our endocannabinoid system. While it is true that the CB1 receptors and CB2 receptors are critical elements of the Endocannabinoid System, they do not comprise the full picture.
The signal that tells your body that there is a problem begins with two signaling molecules, Arachidonoylethanolamine and 2-arachidonoylglycerol.
What are the two signaling molecules?
- Arachidonoylethanolamine (AEA or anandamide)
Anandamide is a neurotransmitter that binds to cannabinoid receptors in the brain and body, stimulating a sense of happiness and mental wellness. Anandamide is a little-known brain chemical that’s been called the “bliss molecule” for the role it plays in producing feelings of happiness.
- 2-arachidonoylglycerol (2-AG)
Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptor.
Your body is smart enough to know that it may need more or less stimulation to modulate pain, inflammation, appetite, anxiety, sleep, immune response, and a host of benefits to achieve homeostasis. Homeostasis is a balance that may require more or less AEA and 2-AG stimulation. Enzymes are a very particular type of protein that will react with the signaling molecules to build up (anabolism) or break down (catabolism) the communication ability of AEA and 2-AG with your endocannabinoid receptors (CB1 and CB2). These enzymes include:
- DAGL-a (for synthesis of 2AG)
- DAGL-B (for synthesis of 2-AG)
- NAPE selective phospholipase-D (for synthesis of AEA)
- MAGL (for breakdown of 2-AG)
- FAAH (for breakdown of AEA)
Anandamide, 2-AG and their CB1 receptors and CB2 receptors, have been the most studied. The latest thinking about the entire ECS has expanded with the discovery of secondary receptors (PPARs) that are now considered part of the endocannabinoid system.
- Three PPARs (Peroxisome Proliferator-Activated Receptors)
PPARs are nuclear transcription factors that regulate antioxidant and anti-inflammatory pathways.
- PPARa – promotes fatty acid (FA) catabolism. Mainly regulates genes involved in the metabolism of lipids and lipoproteins.
- PPARy – enhances insulin sensitivity and lipid storage balancing glucose in the blood.
- PPAR-B – changes the body’s fuel preference from glucose to lipids and suppresses macrophage-derived inflammation.
For most of us, we must acknowledge that we are not doctors and did not go to medical school. Therefore, many of these terms are difficult to pronounce, much less understand their role in our bodies. The easiest way to explain how the Endocannabinoid System works is to compare it to the noise your kids are making in their room while you are trying to relax. Your ears are the neurological signals that travel between nerve endings. You getting up to tell the kids to quiet down is compared to the AEA and 2-AG. The amount of threat you use to quiet the kids is comparable to the enzymes. As you lay back on your couch for peace and quiet is now the homeostasis that you long for. Perhaps this is a little oversimplification but I believe it accurately portrays the system in a way we can all relate to.