The endocannabinoid system (ECS) is a regulatory system found in all vertebrate species, including humans. This system and the natural cannabinoids produced by the body that interact with the ECS serve to maintain homeostasis (Cottone 2013). This means that it sends feedback signals to the cells to ensure that their function is balanced and not overactive or stagnant. Nature, a prestigious scientific journal, published cannabis studies with THC in 1988 that led to the discovery of this system (Marzo 2004). The cannabinoids contained in the cannabis plant interact with the ECS receptors in our body to produce their characteristic effects.

THE ENDOCANNABINOID SYSTEM IN THE CELL RECEPTORS

The ECS is controlled by two types of cell receptors, CB1 and CB2. These receptors are found on the surface of cells throughout the body, with the highest concentrations found in cells of the brain and nervous system. CB1 is much more concentrated in the brain and spinal cord, while CB2 is found mainly in cells of the immune system (Pagotto 2006). Two cannabinoids are naturally produced by the human body and are the signaling molecules that bind to these receptors to perform their function. These internally produced (endogenous) molecules have been identified as anandamide and 2-AG. Once they have performed their function, they are degraded by enzymes. The ECS in our body, which consists of these receptors, naturally produces these cannabinoids and enzymes that help regulate a variety of systems in our body. These systems include pain, appetite, and reproduction, among others.

The high concentration of CB1 in the brain and nervous system is due to its close association with the release and regulation of neurotransmitters (Marzo 1998). High concentrations of these receptors are found at the synapses between neurons. Neurotransmitters are chemicals in the body, such as dopamine and serotonin, that act as signals between neurons. When you feel pain, neurons release neurotransmitters across the synapses from neuron to neuron to tell the brain that something is painful. If these neurons malfunction and keep sending signals, the pain you feel would be unbearable. This is where the ECS comes into play. Endocannabinoids are able to calm overactive neurons and return them to a baseline state of function. This also happens in the opposite direction. Neuron cells that are inactive can be activated by the ECS (Sulak 2018).

A good example is what happens in the gastrointestinal tract or cardiovascular system when cells are not functioning normally. Endocannabinoid levels in the brain increase when a person experiences a stressful event or remembers an unpleasant memory. The ECS serves to protect cells from damage that can result from overactivity due to stressors, but also from inactivity, which can also harm the body.

HOW THE ENDOCANNABINOID SYSTEM CAN AFFECT DISORDERS AND HORMONES

The ECS is also involved in brain functions related to seizures when cells in the brain do not communicate and function normally (Marzo 2004). The FDA has approved Epidiolex for the treatment of seizures in pediatric patients. The active ingredient is CBD, which interacts with the ECS to regulate signaling in the brain and reduce the occurrence of seizures. The ECS plays an important role in regulating this communication and is therefore often treated with medications to alleviate these problems. It also plays a role in the endocrine system, which regulates the release and uptake of hormones. The pituitary gland, which is directly connected to the brain, releases hormones throughout the body that signal everything from hunger to the fight-or-flight response, and has numerous endocannabinoid receptors (Pagotto 2006). The list of functions in the body associated with the ECS is extremely long, but in all cases it serves to maintain the normal functioning of cells in homeostasis.

THE EFFECTS OF CANNABIS & CBD ON THE ENDOCANNABINOID SYSTEM

Cannabis and its cannabinoids have been used for centuries to interact with this complex system in our bodies. The reason we know about the ECS is because cannabis has been widely used throughout history and scientists wanted to know how it works in our bodies (Marzo 2004). Like the endogenous cannabinoids already present in our bodies, THC and CBD are able to interact with the ECS receptors to produce the desired effects. The reason cannabinoids are touted by the pharmaceutical industry is because we have receptors for these molecules all over our bodies. THC binds strongly to CB1 receptors. Because CB1 concentrations in the brain are so high, the psychoactive effects that THC is known for occur. The reason these psychoactive effects don't last forever is because humans already have the enzymes necessary to break down cannabinoids. CBD also interacts with these receptors, although studies have shown that it can actually block CB1 receptors, thereby attenuating the unwanted or psychoactive effects of THC (McPartland 2014). The known appetite-stimulating effect of cannabis may also be associated with the presence of ECS receptors in the gastrointestinal tract and pituitary gland.

CLOSING THOUGHTS

The endocannabinoid system is very complex and keeps our cells and related systems in check. Maintaining a homeostatic balance is essential for survival. Because the ECS is so prevalent in the body and performs regulatory functions, it is a good system to target with prescription medications such as Epidolex and other FDA-approved medications that mimic cannabinoids. Much research is still being done on the exact function of cannabinoids and how they interact with receptors. Scientists are trying to figure out the specific functionality and pathways of these molecules in the ECS in order to develop drugs. Of the top 150 drugs in the U.S., 118 are of plant origin (Roberson 2008). With over 80 unique cannabinoids, cannabis has tremendous potential for multiple interactions with the ECS, and scientists and researchers are eager to find out exactly how these molecules function and whether they could serve as components of drugs in the future.