Getting to know the endocannabinoid system (ECS)

NamasteMD

Cannabis has been used in both medicinal and recreational applications for thousands of years. It may surprise you to learn, then, that the mechanism behind how cannabis worked wasn’t even discovered until the 1960s—specifically 1964. It was the first time scientists were able to determine that Tetrahydrocannabinol (THC) is the main active component in cannabis.

THC is classified as an exogenous cannabinoid, meaning its produced outside of the body. This discovery, funnily enough, ultimately led scientists to discover the Endocannabinoid system (ECS), an internal signaling system designed to help the body maintain homeostasis. As such, the ECS is thought to play a role in regulating mood, appetite, sleep, and learning and memory.

So just what does cannabis have to do with it? Read on to learn more about what the ECS is, how it works with cannabis and how different cannabinoids like THC and CBD interact with your body.

Breaking down key players in the ECS

The ECS is like the body’s intracellular highway. It helps regulate the flow of traffic by modulating cell signalling and responses through endocannabinoids and various enzymes (proteins that bring about a certain action). The response elicited by the ECS, then, is contingent on certain cellular receptors being switched “on” or “off".

Endocannabinoids are lipid-based (fatty) compounds that are naturally produced by the body. These compounds bind to receptors on the surface of the cell that tell the ECS to take action. Some examples of endocannabinoids include 2-AG and anandamide. Anandamide mimics the effects of THC when it binds to receptors in the ECS system, producing a natural “high” in the body.

In contrast to endocannabinoids, we have exogenous cannabinoids—cannabinoids made outside the body. These include THC, CBD, and over 100 other cannabinoids produced by the cannabis plant. Plant derived cannabinoids are known as phytocannabinoids. These exogenous compounds can bind to receptors in the ECS system, mimicking the effects of naturally produced endocannabinoids.

Agonists and antagonists

You can think of cellular receptors as docks on the cell to which a compound binds. Some scientists also use the “key and lock” analogy to convey the concept, but the basic idea is simple. Binding to the CB1 or CB2 receptor will produce unique effects depending on whether or not a compound acts as an agonist or antagonist.

An agonist is a compound that produces a cellular response by binding to its receptors. Its foil is the antagonist, a compound that binds to a receptor and prevents further activation of that cell. In doing so antagonists can prevent other compounds like agonists from binding to these receptors. Some compounds can even act as inverse agonists, meaning they produce the opposite effects of agonists when binding at the receptor site. 

Unfortunately since everyone's body chemistry is so unique, there's no “one size fits all” solution for cannabis. Certain conditions may benefit from activation at receptor sites while others may benefit from inhibition at the site—it all depends on your unique needs.

CB1 receptors

CB1 receptors are found throughout the body’s central nervous system (CNS). They’re also present in several areas of the brain including the hippocampus, cerebellum and hypothalamus. These receptors are thought to modulate perception, memory and movement. Cannabinoids that act as agonists at CB1 site block transmissions of pain and are effective pain relievers. THC, for instance, acts as a partial agonist for both CB1 and CB2 receptors

The intoxicating effects of cannabis are the result of turning CB1 receptors in the brain on or off. THC’s binding at the CB1 site, for instance, produces the distinct feeling of being “high”.

Interestingly enough, these are also the same receptors that determine the intoxicating aspects of cannabis, i.e. whether or not a cannabinoid will make you feel pleasant or paranoid. Some studies have also linked the CB1 receptor gene to fear extinction mechanisms that allow us to forget painful memories. This ability may help patients struggling with Post Traumatic Stress Disorder (PTSD).

CB1 receptors are also thought to play a part in regulating our appetite and sense of satiety after a meal. Compounds that block the activity of CB1—CB1 antagonists such as the phytocannabinoid Tetrahydrocannabivarin (THCV)—are currently being evaluated as potential treatments for obesity.

CB2 receptors

These types of receptors are found in the peripheral nervous system and immune system. They’re associated with regulating pain and inflammation. Research also indicates that activation of CB2 receptors reduces pain

CBD (Cannabidiol) is a non-intoxicating phytocannabinoid with potent anti-inflammatory properties. It interacts with the ECS in a variety of different capacities. CBD can inhibit both CB1 and CB2 receptor sites which is thought to be the reason why CBD reduces negative effects of THC. CBD can also act as an agonist at the CB2 site, which is thought to be the mechanism behind its anti-inflammatory and analgesic properties. 

Other compounds found in the cannabis plant can bind to CB2 receptors. One example is Beta-Caryophyllene, a terpene found in black pepper. Beta-Caryophyllene readily binds to CB2 receptors, a mechanism of action that may explain its anti-inflammatory properties. This is yet another reason why full spectrum medicine—cannabis extracts that preserve all of the plant’s cannabinoids and terpenes—is consistently more effective than consuming an isolated cannabinoid.

Endocannabinoid deficiency 

Some researchers believe endocannabinoid deficiencies may cause disease. The lack of endocannabinoids is called clinical endocannabinoid deficiency (CECD). CECD is thought to potentially be the culprit behind several conditions such as fibromyalgia, irritable bowel syndrome, and migraines.

The great unknown

We’re still doing all we can to learn more about the ECS. After all, cannabis contains over 500 different compounds, many of which are still unknown. Current research suggests that there may be additional receptors beyond CB1 and CB2 in the ECS. These include TRPV receptors, a group of receptors that can be acted on by cannabinoids to potentially produce additional painkilling effects.

Conclusion

The ECS is a system of cellular messengers that helps the body maintain homeostasis. This is accomplished through signalling that takes place at CB1 and CB2 receptors located throughout the body. Functions modulated by the ECS include sleep, mood, memory, and perception.

CB1 receptors are found in the central nervous system while CB2 receptors are located in immune cells. Naturally produced compounds that bind to these receptors are known as endocannabinoids. Phytocannabinoids are produced by plants and can act on the body in a similar manner to cannabinoids. 

The unique ways in which a cannabinoid may affect you is determined by several factors. One of these is whether or not compounds that bind will act as agonists (promoting cell activity) or antagonists (blocking binding). THC and CBD have various effects on the body depending on whether or not they agonize or antagonize these binding sites.