All about the fitness and health lifestyle
All about the fitness and health lifestyle

Understanding the Endocannabinoid System - How Medical Cannabis Works

Last Updated:
July 12, 2023
Kay Nicole

Understanding the Endocannabinoid System - How Medical Cannabis Works

Many of the far-reaching effects of cannabis (and the related cannabinoid THC) have to do with the size and scope of the human endocannabinoid system. Known as the ECS, it is a complex cell-signaling system.

It was only discovered in the 1990s and is still relatively new, but researchers are already investigating ways to utilize it for good health.

What is the Endocannabinoid System?

The ECS is a system of lipids, receptors, and enzymes that regulates homeostasis. It consists of endocannabinoids, chemicals produced by the body, and cannabinoid receptors — proteins that bind with endocannabinoids. The brain and spinal cord contain the most well-known cannabinoid receptors, CB1 and CB2, but other cells also have them.

Your body makes endocannabinoids to control appetite, movement, and mood. These chemical messengers travel between neurons and join with cannabinoid receptors like locks on a door. If a cannabinoid binds to a receptor, it triggers an action such as sweating to cool down or vomiting food to expel toxins.

The ECS is so essential to life that it's found in all vertebrates and some primitive invertebrates. It's also found in plants that humans eat and cannabis, which interacts with the ECS to help us deal with stress and illness. The ECS is a recent discovery, but researchers have already learned much about it. They are continuing to learn how it works and what we can do to stimulate or dampen its effects.


The endocannabinoid system (ECS) is a complex system of chemical messengers and receptors that help to regulate and balance vital bodily functions. It comprises three core components: endocannabinoids, receptors, and enzymes.

Your body produces endocannabinoids, also called endogenous cannabinoids, within your nerve cells. These are lipid-based neurotransmitters, and they work like chemical messengers that send signals between cells. Two well-studied endocannabinoids are anandamide and 2-AG.

Cannabinoid receptors are like miniature portals that sit on the surface of cells throughout your brain, central nervous system, and immune system. They pick up essential signals from your environment and react differently, depending on the situation.

The ECS's fatty acid binding proteins act like molecular canoes transporting the endocannabinoids around your body. Once the endocannabinoids reach their destination, they bind to the receptors like keys fitting into locks. Your body uses these signals to maintain homeostasis, a state of balance and stability that keeps your vital systems working at their best. Per Virginia medical cannabis information, medical cannabis and CBD interact with the ECS to produce their mind-altering and medicinal effects.

CB1 Receptors

The CB1 receptors, first cloned in 1990, are present throughout the brain and modulate various neural functions, including motor activity, learning, and memory. These receptors, located presynaptically on GABA and glutamate neurons, reduce neurotransmitter release by inhibiting VGCC-mediated calcium influx and regulating the enzyme phospholipase Cb. CB1 receptor activation also induces presynaptic long-term depression in excitatory and inhibitory synapses.

In addition to affecting neuronal transmission, endocannabinoids also control pain pathways and have antinociceptive effects in acute, neuropathic, and inflammatory pain conditions.

Phytocannabinoids, found in the cannabis plant, have been used medicinally for over 40 years in oral and synthetic forms to treat chemotherapy-induced nausea and vomiting (dronabinol, nabilone). The most well-known phytocannabinoids are THC, CBD, CBN, and CBC. Unlike endogenous cannabinoids, phytocannabinoids are not subjected to the same rigorous placebo-controlled investigation as Schedule I drugs (THC), which limits their medical availability. However, this does not diminish their effectiveness, as demonstrated by their clinical use.

CB2 Receptors

Regarding pain relief, the CB2 receptors are primarily responsible for modulating analgesia by decreasing cytokine production. The synthesis of these inflammatory mediators potentiates pain signals, and when cannabinoids bind to CB2 receptors, they act as a "brake" that blunts the effects of these cytokines.

CB1 receptors also regulate neurotransmitter release and inhibit the excitotoxicity of presynaptic neurons by binding to the adenylate cyclase receptor. They also promote vasodilation in peripheral tissues by inhibiting the activity of a peptide amide, calcitonin.

Studies that use CB2 agonists have demonstrated antinociceptive activity in various animal models of chronic neuropathic pain. Further, research shows that blocking CB2 receptors produces anxiolytic-like actions in a rodent impulsive behavior model and reduces the reinforcing effects of ethanol.

The Endocannabinoid System and Medical Cannabis

The ECS is a powerful system that regulates many aspects of our health and is deeply involved in almost all bodily processes. This is one of the reasons why it can have such far-reaching effects when triggered by certain substances, including cannabis and some alternative therapies, like exercise, and even dietary choices, such as the Mediterranean diet.

The human body makes endocannabinoids (e.g., anandamide and 2-AG), which bind with cannabinoid receptors throughout the body. The brain's CB1 and CB2 receptors are the main targets of endocannabinoids. In addition to binding with endocannabinoids, chemicals in the cannabis plant, such as THC and CBD, bind with those same receptors. This triggers a chain reaction of other activities that help maintain homeostasis.

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