Have you ever wondered why CBD seems to help with so many different things? The reason is simple. CBD and other plant-based cannabinoids from hemp interact with the Endocannabinoid System, a multifaceted system in our bodies that controls a host of different functions.

Today, we’ll look at what the Endocannabinoid System is, what it does, and why you should ensure it’s working properly to optimize your overall health.

What is the Endocannabinoid System?

You’ve probably heard that CBD works by restoring balance, or homeostasis, to our bodies. This statement is true, but the real reason lies within the Endocannabinoid System or ECS. 

The ECS is our master regulator, responsible for ensuring all the complex mechanisms in our bodies are functioning and interacting properly. It evolved over 600 million years ago and is present in all mammals, reptiles, fish, and invertebrates. But despite its ancient history, scientists only began studying it in the late 1980s. However, what we do know can change the way we think about our health, as evidence suggests endocannabinoid deficiency could be the root of countless diseases. 

How Does the Endocannabinoid System Work?

The Endocannabinoid System controls homeostasis by reading signals from other major players in our bodies, including the Central Nervous System, Peripheral Nervous System, Immune, and Endocrine Systems. There are three essential elements to the ECS to understand this ability:

1. CB Receptors – There are two central receptors in the ECS: CB1 and CB2. CB1 receptors are mainly concentrated in the brain, while CB2 are found in the peripheral organs and white blood cells 
2. Endocannabinoids – Our bodies naturally synthesize cannabinoids. These include anandamide and 2-Arachidonoylglycerol (2-AG). 
3. Enzymes – These include fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

The CB receptors read incoming signals and communicates back and forth through a negative feedback loop of endocannabinoids, which are quickly produced and broken down by the enzymes. CB receptors are also G-protein coupled, meaning they can directly influence incoming signals. While most receptors can only amplify or diverge signals, the CB receptors can completely override them.

Take inflammation, for example. Inflammation is a natural response to injury and infection, but too much can cause us pain and damage cells. It's the ECS's job to turn off inflammation once it is no longer necessary. The CB receptors in the surrounding immune cells and tissues recognize the inflammation and secrete cannabinoids to slowly reduce the inflammatory response.

In addition to regulating inflammation, the Endocannabinoid System is also responsible for balancing:

• Appetite and metabolism
• Communication between cells
• Immune Response
• Memory
• Mood
• Pain sensation
• Sleep

However, even our ECS can fall out of balance. To stimulate the ECS and bring our bodies back into harmony, many people have turned to plant-based cannabinoids from hemp or cannabis, as these molecules mirror endocannabinoids. 

How does CBD Affect the Endocannabinoid System?

Unlike THC, which interacts directly with the CB1 receptors in the brain, CBD has a weak binding affinity to both CB receptors. Instead, CBD interacts indirectly with the Endocannabinoid System.

Preclinical studies have shown CBD affects non-cannabinoid neurotransmitters, ion channels, and receptor-independent pathways that influence the signals received by the CB receptors. Some of these mechanisms include:

Vanilloid Receptors – Technically called transient receptor potential cation channel subfamily V (or TPRPV), these ion channels mediate our pain perceptions, inflammation, and body temperature. CBD binds to TRPV1, which could explain anti-inflammatory anecdotal evidence. This receptor is also responsible for mediating the effects of many different medicinal herbs, including eugenol from vanilla and capsaicin from hot chili peppers. 

Serotonin Receptors – In high doses, CBD directly activates the 5-HT1A (hydroxytryptamine) serotonin receptor. Serotonin, or 5-HT, triggers our body to either have an increased or reduced response to anxiety, addiction, appetite, sleep, pain, and nausea. 

Allosteric Modulation – Allosteric modulators, like CBD, can change a receptor's shape, thus enhancing or inhibiting how a receptor transmits a signal. CBD is a positive allosteric modulator of the GABA-A receptor, meaning it widens its shape. Gamma-aminobutyric (GABA) receptors play an essential role in controlling fear and anxiety when neurons become overexcited. CBD is thought to reduce anxiety by amplifying its calming nature. 

CBD is also a negative allosteric modulator to the CB1 receptor, meaning it makes the receptor’s shape smaller. This effect is how CBD can reduce adverse side effects like paranoia and anxiety from THC by weakening the receptor’s ability to bind with it. 

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