What Is the Endogenous Cannabinoid System?

The human body possesses a widespread cell-signaling network known as the Endocannabinoid System (ECS). This system acts as a master regulator, maintaining a stable internal environment, a state scientists call homeostasis. Its discovery in the early 1990s resulted from research into how cannabis affected the body, but the ECS is a fundamental part of physiology that functions within everyone.

Present throughout the central and peripheral nervous systems, organs, and tissues, the ECS modulates communication between different cells. It helps ensure that bodily processes operate within a healthy range, adapting to internal and external fluctuations.

The Three Key Components

The endocannabinoid system is comprised of three main parts that work in concert: endocannabinoids, receptors, and enzymes. Endocannabinoids are signaling molecules produced naturally by the body as needed. The two most well-understood of these are N-arachidonoyl ethanolamine, more commonly known as anandamide, and 2-arachidonoylglycerol, or 2-AG. Anandamide, often called the “bliss molecule,” and 2-AG are synthesized from fat-like molecules within cell membranes.

These messages are received by specialized cannabinoid receptors found on the surface of cells. The two primary types of receptors are cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). CB1 receptors are one of the most abundant receptor types in the brain and central nervous system, influencing memory and mood. CB2 receptors are found mostly in the peripheral nervous system and are particularly concentrated in immune cells, playing a part in managing inflammation.

Once anandamide and 2-AG have delivered their signals by binding to these receptors, they are broken down by metabolic enzymes. This process ensures that the endocannabinoids are used only for as long as they are needed. The enzyme primarily responsible for degrading anandamide is fatty acid amide hydrolase (FAAH), while the breakdown of 2-AG is handled mainly by the enzyme monoacylglycerol lipase (MAGL).

What the Endocannabinoid System Regulates

The influence of the endocannabinoid system is extensive, touching upon a wide array of physiological and cognitive processes to maintain the body’s equilibrium. Its regulatory functions include:

• Mood and stress response: By modulating neurotransmitter release in brain regions associated with emotion, the ECS helps to buffer the effects of stressful situations and promote a sense of well-being.
• Appetite and digestion: The system helps manage appetite, digestion, and energy balance. ECS signaling in the brain can stimulate hunger, while its activity in the gut can influence intestinal motility.
• Sleep: The ECS influences sleep-wake cycles, and endocannabinoid levels fluctuate throughout the day and night. This function is tied to its role in calming the nervous system and promoting restorative rest.
• Pain and inflammation: The system is deeply involved in how we perceive pain and how our bodies manage inflammation, dampening pain signals and reducing inflammatory responses at injury sites.
• Memory and learning: Its functions extend to memory and learning, demonstrating its broad reach in maintaining daily cognitive health.

Exogenous Cannabinoids and the ECS

While the body produces its own endocannabinoids, the system can also be influenced by external compounds known as exogenous cannabinoids, primarily those found in the cannabis plant. The most well-known of these is delta-9-tetrahydrocannabinol (THC), the component of cannabis responsible for its psychoactive effects.

THC exerts its influence by directly binding to CB1 receptors in the brain, much like the endocannabinoid anandamide. However, THC’s structure allows it to bind more strongly and for a longer duration. This potent and sustained activation of CB1 receptors is what disrupts normal brain communication and produces the characteristic “high.”

In contrast, cannabidiol (CBD), another prominent phytocannabinoid, interacts with the ECS in a more indirect manner. CBD does not have a strong binding affinity for either CB1 or CB2 receptors. Instead, one of its primary mechanisms is to inhibit the FAAH enzyme, the protein that breaks down anandamide. By slowing the degradation of anandamide, CBD can increase the levels of this endocannabinoid in the body, allowing it to exert its natural calming effects for longer. This indirect influence is why CBD does not produce the intoxicating effects associated with THC.

Supporting a Healthy Endocannabinoid System

A person can take several lifestyle measures to support the health and proper functioning of their endocannabinoid system, often referred to as improving “endocannabinoid tone.” Diet is an important element, as the building blocks for endocannabinoids are derived from dietary fats. Specifically, the consumption of omega-3 fatty acids, found in foods like fatty fish, flaxseeds, and walnuts, is important for the synthesis of 2-AG and anandamide.

Regular physical activity is another effective way to modulate the ECS. Aerobic exercise, such as running or cycling, has been shown to increase circulating levels of anandamide. This rise in anandamide is believed to contribute to the euphoric feeling sometimes experienced after sustained exercise, often called a “runner’s high.”

Managing stress is also important for maintaining a healthy ECS, as chronic stress can lead to its dysregulation. Practices that promote relaxation and mindfulness, such as yoga, meditation, and deep-breathing exercises, can help restore balance. Certain botanicals beyond cannabis, like caryophyllene—a terpene found in black pepper, cloves, and rosemary—can also interact with the ECS by binding to CB2 receptors, potentially offering another avenue for natural support.