Explaining Cannabinoids Part II: The Endocannabinoid System
In our last post in this series, we reviewed the phytocannabinoids—what they are and some of the effects research shows they have on the human body. Equally important is understanding why these phytocannabinoids do what research suggests. This question has been the focus of rigorous study for decades and has led directly to the discovery of one of the body’s most important systems: the endocannabinoid system.
What is the Endocannabinoid System?
The short answer is that the endocannabinoid system is what keeps the body balanced. Studies show the endocannabinoid system modulates pleasure, energy, and well-being, and also helps the body find equilibrium when affected by injury or disease. The system is active in all parts of the body and interacts with all of the body’s other systems. Despite its significant role, an informal poll in 2014 showed only 13 percent of US medical schools cover the endocannabinoid system when training new doctors.
Part of that lack of training is likely due to the endocannabinoid system’s relative newness to the scientific community. The first cannabinoid receptor was discovered in 1988, and researchers are constantly making breakthroughs on how the system functions.
Elements of the Endocannabinoid System
The endocannabinoid system is named for natural compounds in the human body that resemble the phytocannabinoids found in cannabis (both marijuana and hemp plants). Our current understanding shows it is made up of the following parts:
- Two receptors:Cannabinoid-1 (CB1) receptor, Cannabinoid-2 (CB2) receptor
- Two signaling molecules: arachidonoyl ethanolamide (also known as AEA or anandamide), 2-arachidonoyl glycerol (2-AG)
- Five Enzymes: DAGL-a, DAGL-b, NAPE selective phospholipase-D, MAGL, FAAH
CB1 and CB2 receptors are found throughout the body. CB1 receptors are predominantly found in the brain and nervous system, while CB2 receptors are mostly found throughout the rest of the body—particularly in the immune system. Some tissues contain both CB1 and CB2 receptors, each carrying out a different action.
AEA and 2-AG are unique in that they are not stored in any one place in the body, but rather exist as molecular parts that coalesce wherever and whenever they’re needed. When CB1 or CB2 receptors increase in one part of the body, AEA and 2-AG are constructed, take action, and break apart within seconds. Both AEA and 2-AG are capable of activating CB1 and CB2 receptors.
The metabolic enzymes perform the critical function of breaking down AEA and 2-AG when they are no longer needed.FAAH breaks down AEA, while MAGL is responsible for breaking down 2-AG. While these enzymes are effective at dissolving endocannabinoid molecules, they are not great at breaking down phytocannabinoids, which will come in to play in just a bit.
How the Endocannabinoid System Works
The endocannabinoid system is present in the entire body and affects every one of the body’s many systems. However, it isn’t active across the entire body at once. If imbalances or injuries occur, endocannabinoid receptors pinpoint the specific area in need of aid. The exact function of the endocannabinoid system is drastically different depending on their location in the body and the specific need of the time.
For instance, activated brain-based CB1 receptors have been shown to create feelings of pain relief, anxiety relief, and mood stabilization. Activated CB2 receptors in the brain function as a local anti-inflammatory—which may be beneficial to certain ailments like Alzheimer’s Disease, which have been linked to chronic brain inflammation.
How the Endocannabinoid System Regulates Bodily Functions
Each of these general categories of action—anti-inflammatory, anti-anxiety, etc.—requires coordination of many different cells fulfilling different functions. The endocannabinoid system acts as a communication network between these cells. For example, when an injury occurs, endocannabinoids decrease the release of activators from the injured tissue, stabilize the nerve cell, and calm immune cells.
In addition to aiding with recovery from injuries, endocannabinoids are important in proper brain function. Neurons (brain cells) are in constant communication with one another, sending off electrochemical signals to their partner neurons. If a neuron becomes overactive and sends too many signals, a “listening” neuron will create endocannabinoid molecules and send them to bind to the overactive neuron’s CB1 receptor.
How Phytocannabinoids Interact with the Body
Phytocannabinoids like CBD and THC produce their effects by interacting with the receptors, molecules, and enzymes that make up the endocannabinoid system. For instance, THC binds to CB1 receptors in the brain, producing a psychoactive high. As mentioned earlier, FAAH and MAGL can’t effectively break down phytocannabinoids, which means THC activates the CB1 receptor for much longer than AEA or 2-AG.
For decades, this psychoactive high was the only thing cannabis researchers were concerned with. While Cannabidiol (CBD) was discovered some time ago, it was assumed to be an inactive compound since it was not psychoactive. Recent research has shown that CBD interacts with the body’s systems in a much different way.
Unlike THC, CBD does not bind to CB1 and CB2 receptors. CBD instead works by inhibiting the FAAH enzyme in the brain, which allows for larger quantities of AEA to exist for longer. This results in an increased activation of CB1 receptors by the body’s natural cannabinoids. Some studies suggest that inhibiting FAAH and increasing AEA presence may be an effective way of treating anxiety disorders.
In addition to limiting enzyme activity, CBD also communicates with CB receptors and affects their ability to bind with other compounds. CBD causes CB1 receptors to change their shape, making it so THC cannot bind to them.
By increasing AEA presence and activity, cannabidiol also provides support to anti-inflammatory and immune functions throughout the entire body. The specifics of how CBD functions in these immune and anti-inflammatory contexts are still up for debate, in large part due to the uncertainty surrounding how CBD interacts with CB2 receptors.
Looking Forward: More Research, More Understanding
As this suggests, study of both endocannabinoids and phytocannabinoids is a developing field. We’re still learning how and why these compounds function the way they do, which is what makes hemp products such an exciting area to learn about.
The most important thing to take away is that it is all about homeostasis: the endocannabinoid system is working constantly to keep things like body temperature, appetite, pain, and stress at a happy medium. While the body is largely capable of regulating these functions in most normal circumstances, sometimes phytocannabinoids may be helpful in finding and maintaining that state of equilibrium.
This article is by no means all-encompassing, but it should give you a great place to start as you continue to learn more about CBD and hemp products with Apotheca.
This post references CBD: A Patient’s Guide to Medicinal Cannabis by Leonard Leinow & Juliana Birnbaum throughout. To purchase the book, you can click here.