CB1 and CB2 Receptors:  How Does the ECS Work?

CB1 and CB2 Receptors: How Does the ECS Work?

The endocannabinoid system’s most important function is to maintain homeostasis. It does this by leveraging endocannabinoids and CB1 and CB2 cannabinoid receptors in the central and peripheral nervous systems and the immune system. When the body detects an imbalance with a process regulated by the ECS, it produces cannabinoids that interact with receptors. This generates a chemical process that targets and resolves the imbalance and returns the body to a state of homeostasis, or perfect balance. 

If you've investigated the differences between THC and CBD, you may already know that these chemicals affect the brain and body in distinct ways due to the receptors (proteins) they bind to. These receptors, called cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), determine the behavioral effects of cannabis when consumed, as well as the effects of your body’s own cannabis chemicals, 2-AG and anandamide.

The endocannabinoid system (ECS) is a relatively unknown system of the body with a considerable influence on human health and well-being. The ECS is composed of cannabinoid receptors, endocannabinoids, and metabolic enzymes, playing a crucial role in the human body: maintenance of homeostasis via various physiological and regulatory mechanisms.

A “receptor” is typically defined as an intracellular protein molecule that receives and responds to extracellular chemical signals, ultimately producing a cellular cascade of events. Cannabinoid receptors (CBs) are the primary targets of the ECS, bound by lipid signaling molecules called endocannabinoids (eCBs) that are produced on demand in response to elevated intracellular calcium levels in neurons. After eCBs bind a receptor to inhibit the release of neurotransmitters and exert a particular effect on the body, they are degraded via metabolic enzymes in a process called hydrolysis.

While eCBs are endogenous to the human body, there are two other types of cannabinoids that can bind CBs: phytocannabinoids (plant-based chemicals) and synthetic cannabinoids (designed specifically to interact with the ECS). Two of the most-studied eCBs include N-archidonylethanolamide (anandamide, AEA) and sn-z-archidonoylglycerol (2-AG).

There are two main types of CBs, which vary in their chemical structure and thus perform different functions in terms of diet, lifestyle, and nutrition. 

CB1 receptors are located in the brain and throughout the body, while CB2 receptors are found mostly in the immune and gastrointestinal system; although CB2 receptors are also found in the brain, they are not expressed quite as densely as CB1 receptors. In addition, THC (the psychoactive component of cannabis) binds more closely to the CB1 receptor than the CB2 receptor. 

Cannabinoid Receptor 1 (CB1)

CB1 receptors are G protein-coupled cannabinoid receptors that reside in the nerve cells of the brain and the spinal cord. They are also present in organs like the spleen as well as the white blood cells, endocrine gland, and urinary, gastrointestinal, and reproductive tracts. In the brain, CB1 receptors are most prevalent in the hippocampus and amygdala, both of which play essential roles in memory and emotional regulation. CB1 receptors modulate neurotransmitter release and are some of the most common receptors in the nervous system. In the brain, CB1 receptors affect spinal cord regions, which explains why cannabinoids impact memory, pain regulation, and motor control. 

Cannabinoid Receptor 2 (CB2)

CB2 receptors help modulate inflammation and immune response. They are found within the nervous system, with high concentrations also being present in the spleen, gastrointestinal tract, and immune system. Unlike CB1 receptors, however, there are very few CB2 receptors in the brain. CB2 receptors play an essential role in immune function, pain management, and inflammation. They also govern behaviors associated with reward and addiction by regulating dopamine production and activity within the ventral tegmental brain area

Hemp, also known as the fiber and seeds from the Cannabis sativa L. plant species, contains a negligible amount of THC. Instead, the phytocannabinoids found in hemp largely activate CB2, thus exerting positive, non-psychoactive effects on the human body. 

Many researchers looking into these receptors may one day help us learn more about how different types of cannabinoids could help people based on their unique expression of CB1 and CB2 receptors throughout the body and brain.

Cannabinoids and the ECS

The body’s naturally-occurring endocannabinoids, such as AEA and 2-AG, are very similar to cannabis-derived cannabinoids like CBD and THC. In fact, researchers currently believe that consuming cannabinoids may help the ECS maintain homeostasis within the body. 

The ECS and CBD

Unlike THC, CBD does not bind to CB1 or CB2 receptors. While some cannabinoids bind directly to cannabinoid receptors, CBD interacts indirectly with the receptors. Specifically, CBD activates TRPV1 receptors (vanilloid receptor 1 or capsaicin receptors). This partnership creates a variety of positive effects within the body – including promoting a sense of well-being and encouraging higher levels of anandamide production. 

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