Cannabinoids have been receiving more and more attention in the news lately and you may find yourself wondering: what is the endocannabinoid system and what role does it play in the human body? In this series of blog posts, we will explore the endocannabinoid system and how it works to keep the human body in balance, look at current research and advancements in the field and glance ahead into the future of endocannabinoids.


human endocannabinoid systemSource: Drug Discovery Today, Vol 22, Issue 1, January 2017

In order to understand the endocannabinoid system, it’s also important to understand the key biological concept of “homeostasis”, which refers to any process or reaction that the body utilizes to actively maintain a stable internal environment. In many cases, these functions geared towards maintaining balance are necessary for any organism to survive. Disturbances to physiological equilibrium, if uncorrected, can lead to impaired health, with symptoms that range from headaches to more serious diseases like arthritis, epilepsy, stroke, obesity, Alzheimer’s disease, cancer, and glaucoma. The body’s ability to adjust to changes and maintain homeostasis directly impacts the state of health of that organism.

The endocannabinoid system is a molecular system responsible for regulating and balancing many processes in the body, including immune response, communication between cells, appetite and metabolism, memory, and more. It is through this system of receptors and metabolic enzymes that cannabinoids interact with the human body and trigger beneficial effects. Despite the integral role the endocannabinoid system has in human body function, it was discovered relatively recently and much of its importance is only just becoming understood by scientists and the medical community at large.

A Brief History of the Endocannabinoid System

“Relax, eat, sleep, forget and protect.” ~ Vincenzo Di Marzo

In 1998, Vincenzo Di Marzo, one of the world’s leading cannabinoid scientists, stated that these physiological processes in the human body: mood, appetite, sleep, memory, and pain-sensation are in the domain of a biological regulatory system wired to keep the body in balance.

Named after the plant that led to its discovery, the endogenous cannabinoid system is perhaps the most important physiologic system involved in establishing and maintaining human health. It is composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are found throughout the body in the brain, organs, connective tissues, glands, and immune cells. In each tissue, the cannabinoid system performs different tasks, but the goal is always the same: homeostasis. In fact, almost every physiological process is affected by the endocannabinoid system on some level. This means it can be targeted to treat many diseases.

What is surprising is that the endocannabinoid system was discovered less than 30 years ago.

In 1964, Dr. Raphael Mechoulam, the godfather of cannabis research, first identified and isolated tetrahydrocannabinol (THC) for the first time. THC is historically known for its psychoactive properties. In addition, Mechoulam also successfully isolated cannabidiol (CBD), a non-psychotropic cannabinoid and generally associated with antioxidant and neuroprotectant properties. These cannabinoids are referred to as "phytocannabinoids" because they are naturally occuring in plants. Being able to isolate these phytocannabinoids for the first time was a critical stepping stone in discovering the endocannabinoid system.

In 1990, a molecular biologist, Lisa Matsuda and her colleagues at the National Institute of Mental Health identified a THC-sensitive receptor in lab rat brains. This was the first time the endocannabinoid system was defined. Shortly thereafter, Mechoulam’s research led him to the discovery of two endocannabinoids: anandamide and 2-arachidonoylglycerol, or 2-AG. Endocannabinoids are cannabinoids that are naturally produced in the body by the brain. These endocannabinoids bind to cannabinoid receptors on target cells throughout the body, triggering a cellular response which is amplified or diminished as metabolic enzymes destroy or make more endocannabinoids. This activity produces diverse effects that range from anti-inflammatory responses to euphoria. 

“By using a plant that has been around for thousands of years, we discovered a new physiological system of immense importance. We wouldn’t have been able to get there if we had not looked at the plant.” ~ Mechoulam

These discoveries triggered an explosion of research exploring the endocannabinoid system. The system has been implicated in multiple physiological functions and we now have valuable knowledge about the pharmacology, biochemistry, and clinical effects of endocannabinoids. It has been established that endocannabinoids have a role in the pathology of many disorders and it is believed that they also serve a "protective role" in many medical conditions. Diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system. 

Cannabinoid Receptors: What They Are and What They Do:

cannabinoid receptorsSource: the-human-solution.org

There are at least two types of cannabinoid receptors. Many of the effects of cannabinoids and endocannabinoids are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although there is new evidence that additional receptors may be involved.

CB1 receptors are primarily found in several brain regions and the central nervous system. They are also found in the cerebellum and in both male and female reproductive systems. These receptors mediate many of the psychoactive effects of cannabinoids. CB2 receptors are predominantly distributed in the immune system. They appear to be responsible for anti-inflammatory and other immune-related activity.

The two primary endocannabinoids produced by the human body interact directly with these receptors. Anandamide’s main focus is to activate CB1 receptor, however, it does have a lower tendency towards the CB2 receptor. 2-AG, interacts with the CB2 receptors. 

The cannabis plant happens contains phytocannabinoids - plant-based substances with an affinity for the cannabinoid receptors.

molecular structure endocannabinoids and phytocannabinoid cbd

Wait, There’s More! Cannabinoid Receptors You Probably Haven’t Heard About:

There is new evidence that suggests that the endocannabinoid system is more complex than first believed. Since 1999, we have learned that cannabinoids were still able to affect blood pressure, pain, inflammation, and gastric motility in the absence of CB1 and CB2 receptors. This led to the discovery of at least eight other receptors to which cannabinoids bind. GPR18, GPR55, GPR119 have functions in the immune system, CNS, and gastrointestinal systems respectively, while others are capable of regulating pain transmission and cellular function.


Sources:

https://www.ncbi.nlm.nih.gov/pubmed/27086601

https://www.sciencedirect.com/science/article/pii/S1359644616302926

http://profofpot.com/endocannabinoid-receptors/


In the next installment of this series, we will delve deeper into the phenomenon known as “The Entourage Effect” and its benefits to the human body.