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CB2 Receptors & the Role They Play

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
  • The endocannabinoid system comprises two different types of receptors (cannabinoid CB1 receptors and cannabinoid CB2 receptors), which help send messages to different areas of the body to help bring balance and regulation to bodily systems. 

    Endocannabinoids made by the body bind to these receptors, activating them and helping them establish homeostasis.

    C15:0, the only ingredient in fatty15, can support your body’s ability to make PDC (pentadecanoylcarnitine), the second-ever discovered, fully-acting endocannabinoid. 

As we learn more about the role and physiology of the endocannabinoid system in our bodies, we’re better able to understand how stimulating this system can help us keep our bodies balanced and even lower our risk of age-related diseases. 

Two integral parts of the system, the CB1 and CB2 receptors, help activate the system and are responsible for the messaging that helps our bodies achieve homeostasis. It sounds complex, but we’ll break it down and make it easier to understand the specific role CB2 receptors play in the body and how activating them can promote your well-being. 

What Is the Endocannabinoid System?

If you aren’t familiar with the endocannabinoid system, you might be tempted to write it off as a system designed to interact solely with cannabis. Although there are plant-based compounds found in cannabis that can interact with the endocannabinoid system (ECS), like tetrahydrocannabinol (THC) and cannabidiol, the system is much more complex. 

Your body has an internal process for stimulating the system that doesn’t require cannabis. The ECS is a web of receptors throughout your body that play a role in the regulation and function of numerous bodily processes and functions. These receptors work on feedback loops.

Feedback loops are a three-part system.

  1. Receptors made from amino acids in the ECS collect data from external stimuli and send messages to a control center that environmental changes require attention.

  2. The control center, the central nervous system (CNS), including the brain and spinal cord, processes the information and decides the action needed to bring the body back to its homeostatic state. 

  3. The control center sends out effectors, which make the necessary changes to the body to bring it back into balance. 

      An example of this is temperature regulation. When the receptors sense a change in the external environment causing the body’s core temperature to drop, it sends the message to the control center. The control center then sends effectors to raise the body’s core temperature. 

      There are two types of feedback loops; positive feedback loops, which cause the body to produce more of something (like a hormone), and negative feedback loops, which tell the body to stop producing something. The goal of each type of loop is to keep the body regulated. 

      Now, let’s consider the types of receptors involved in the feedback loops.

      What Are Endocannabinoid Receptors?

      There are two specific types of cannabinoid receptors in the ECS. 

      • CB1 Receptors. These receptors are located in the brain and spinal cord. They control functions like emotion and mood, sleep, development of the body, and some parts of cognitive function and memory. 
      • CB2 Receptors. These receptors, which will be the focus of the remainder of our study, are located in parts of the peripheral nervous system, in the immune cells of the immune system, and in the digestive system. 

      Although there are more CB1 receptors than CB2 receptors, CB2 receptors actively interact with the CB1 receptors such that modulation of them can have a profound impact on the functions regulated by the CB1 receptors, too. 

      The Role of CB2 Receptors

      CB2 receptors (CB2Rs) play an important role in your immunity and parts of your immune system you probably haven’t considered, like digestion and even your ability to focus. 

      Immunity

      Because most CB2 receptors are found in immune tissue, it’s not surprising that these receptors regulate many of the signaling pathways that control our immunity. 

      The CB2 receptor expression is located in most immune cell types, which means these receptors find their home in cells like B cells, T cells, and white blood cells. These cells are often associated with inflammation. While some inflammation is good and necessary (like when you have a wound), some can lead to disease. 

      Chronic, low-level inflammation is often associated with heart disease, type 2 diabetes, and unhealthy blood pressure. In mouse model studies, receptor activation of cannabinoid receptor type 2 with selective agonists was associated with lower levels of inflammatory response compared with animals that do not have CB2Rs. 

      Digestion 

      The presence of CB2Rs in the digestive tract helps ensure more than just our regularity. Certain intestinal conditions, like IBS, can be debilitating and painful. CB2Rs are involved in the modulation and regulation of this neuropathic pain.

      Because CB2Rs exist in the gut, they are connected to CB1 receptors. The receptor signaling between CB2Rs and CB1 receptors explains why CB2Rs are also involved with functions usually controlled by CB1 receptors, like cognitive function. 

      Cognitive Function

      Although the CB1 receptors are most common in the brain, the relationship between the CB2Rs in the immune system and the CB1 receptors helps further regulate processes like cognitive function. 

      For instance, studies show higher levels of inflammatory cells called cytokines, kynurenine metabolites (molecules that control signaling between gut flora and immune cells), and higher levels of microglial activation (a symptom of neuroinflammation) underlie cognitive disorders and diseases

      Additionally, CB2Rsinteract with certain neurotransmitters like acetylcholine, dopamine, and noradrenaline.

      How Do We ActivateCB2 Receptors?

      Being able to stimulate and activateCB2Rs can help us bring balance to the body and may even be a newly discovered way to avoid illness associated with a lack of CB2 receptormodulation. 

      To activate these little guys, we need cannabinoid receptor agonists or cannabinoids. There are three ways to get them. 

      Phytocannabinoids

      As we discussed, the cannabis-sativa plant contains several compounds that can bind to the receptors in the ECS. Only THC can bind to both CB1 and CB2 receptors, but its psychoactive side effects make it hard for us to use it therapeutically. 

      Synthetic Cannabinoids

      We can create cannabinoids in a lab setting, and some have even been approved to treat conditions like severe nausea in cancer patients undergoing chemotherapy. 

      Endocannabinoids

      Your body makes its own endogenous (aka made naturally inside of the body) cannabinoids that activate the receptors in the ECS. There are three known endocannabinoids.

      • Anandamide. This endocannabinoid can only bind to CB1 Receptors and was the first endocannabinoid ever discovered.
      • 2-Arachidonoylglycerol (2-AG). The first ever fully-acting endocannabinoid, 2-AG can bind to both CB1 and CB2 receptors. 

      For years we have believed these were the only two endogenous cannabinoids the body could produce, but new studies have discovered another fully-acting endocannabinoid called pentadecanoylcarnitine (PDC).

      How Is PDC Made?

      All endocannabinoids are made from fatty acid synthesis and are broken down by particular enzymes in the body. Anandamide, for instance, is made from fatty acid amide hydrolase. Fatty acids are lipids that are chained together. 

      PDC is made from the synthesis of carnitine and pentadecanoic acid, also known as C15:0. C15:0 is an essential fatty acid, which means that our bodies need it to thrive, but can’t readily make it on their own. Thankfully, there’s a solution. 

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      Fatty15: The C15:0 Solution

      C15:0 is an odd-chain, saturated fatty acid found in trace amounts in whole dairy products and some fish. However, simply increasing your intake of these foods would mean packing in extra calories and intaking some bad, even-chain saturated fat. 

      Don’t worry; there’s a new supplement that can restore your circulating levels of C15:0 and help your body make the PDC it needs.* It’s called fatty15.

      Fatty15 was born from scientific discovery and contains just one ingredient, FA15™. This pure, vegan-friendly, sustainably produced, award winning ingredient is just what your body needs to synthesize PDC and help activate your CB2 receptors.* 

      In addition, fatty15 supports your cells, the foundation of your health. 

      • By integrating into cell membranes, fatty15 helps keep cells strong and supported so intracellularactivities can continue.*
      • As we age, the mitochondrial function in our cells decreases. Fatty15 improves mitochondrial function by 45%, powering your cells to give you the energy you need.* 

      Just one little capsule per day can profoundly impact your health and help give your body the ingredients it needs to produce CB1 and CB2 agonists like PDC.* 

      Better Health Through the ECS

      The neuroscience behind the endocannabinoid system is burgeoning, and we know that activating the receptors in the ECS is a therapeutic target for establishing a better baseline of wellness in our bodies. In fact, fully acting endocannabinoids are often referred to as the ‘holy grail of health’.

      Taking fatty15 can help support your body’s ability to produce its own endocannabinoids, which can help keep your body and mind balanced and healthy. 

      Sources:

      The CB2 receptor and its role as a regulator of inflammation - PMC

      The endocannabinoid system: Essential and mysterious - Harvard Health

      Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders - PubMed

      Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health | Scientific Reports

      The relationship between immune and cognitive dysfunction in mood and psychotic disorder: a systematic review and a meta-analysis | Molecular Psychiatry

      Cannabinoid Receptor Type 2 - an overview | ScienceDirect Topics

      Profile photo for Eric Venn-Watson

      Eric Venn-Watson M.D.

      Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.

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