The issue of the validity of the medical efficacy of cannabis cannot be approached by patients, students, or physicians without a solid foundational knowledge of the chemical building blocks behind the mythical herb’s nuanced—and largely unresearched—interaction with the human body.
This article will review the fundamental molecular system behind the health benefits derived from what, for most of the 20th century’s era of cannabis prohibition, was referred to in North America as “marijuana” or “pot.”
“The endocannabinoid system exists throughout our body and serves as a control center. When the receptors are activated, the resulting chemical reaction optimizes the behavior of each cell. In the case of cancer, apoptosis…programmed death…results, while healthy cells are simultaneously protected.”
—Mara Gordon, medical cannabis researcher, 2018
To understand how and why cannabis and its constituent parts can do things like put Crohn’s Disease into remission or dramatically reduce the number of seizures suffered by an epilepsy patient, readers must first possess a solid understanding of the plant- and human-based elements of this mechanism and the basic manner in which they interact.
Readers and students shall gain an overview of the following elements:
- The Endocannabinoid System.
- CB1 and CB2 cellular receptors.
- The endocannabinoids anandamide and 2-arachidonoylglycerol.
- The phytocannabinoids tetrahydrocannabinol and cannabidiol.
- The role of homeostasis in health and wellness.
- Clinical Endocannabinoid Deficiency Syndrome.
The physiology of all mammals, not only humans, features something called the Endocannabinoid System, or ECS (also denoted as eCS). The ECS is a collection of microscopic receptors located on the surface of a wide variety of cell types within the body. This system of receptors blankets the cells of two main regions of the body: The Central Nervous System (CNS) and the immune system.
Two types of ECS receptors have been discovered to date: CB1 and CB2. Other receptors, such as GPR55, have been credibly theorized, but not yet proven. While both receptor types are found throughout all regions of the body, CB1 is concentrated in the CNS (the brain and spinal cord), while CB2 receptors are found mostly within the organs and tissues of the immune system that are located throughout the body.
Considered in a vacuum, the ECS alone is like a sports car lacking a driver. Only a very limited set of molecules are permitted to fit into its specialized receptors. These chemicals, called cannabinoids, can be obtained from two sources: One’s own body or an outside plant source such as the cannabis herb. Cannabinoids produced within the body are known as endocannabinoids, while those obtained from plants are labeled phytocannabinoids.
First discovered in 1940 by Roger Adams in the United States and again in 1964 by Dr. Raphael Mechoulam in Israel, cannabinoids have been found to work synergistically with the human body and, more specifically, the ECS.
Anandamide and 2-arachidonoylglycerol (2-AG) are the major endocannabinoids manufactured by the human body. The most common phytocannabinoids available from cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). While these are the most abundant in most strains of cannabis, dozens of other phytocannabinoids may be present, including:
- Tetrahydrocannabivarin (THCv): Acts as an appetite suppressant, is helpful for some diabetics, and is more common in sativa strains.
- Cannabigerol (CBG): Helpful for diseases such as cancer and Crohn’s Disease (the acidic precursor, CBG-A, is the origin of all other cannabinoids).
- Cannabinol (CBN): Effective for insomnia and sleep disorders; results from degraded (“stale”) THC after prolonged storage or exposure to light or air.
The ECS is involved in many critical physiological processes, including appetite, sleep, energy level and metabolism, pain sensitivity, memory, and even mood. This is one reason that cannabis has been found to help patients suffering from the anxiety and severe depression of conditions such as Post Traumatic Stress Disorder.
“Homeostasis is the concept that most biological systems are actively regulated to maintain conditions within a narrow range. Our body doesn’t want its temperature to be too hot or too cold, blood sugar levels too high or too low, and so on.”
— Dr. Nick Jikomes, Ph.D., neuroscientist, 2016
When the ECS and other systems of the body are free of disease—and, thus, working in balance and harmony—it is a desirable and healthy condition called homeostasis. Like a vitamin or mineral deficiency, a lack of cannabinoids within the ECS is called endocannabinoid deficiency (also known as Clinical Endocannabinoid Deficiency Syndrome, or CEDS). CEDS is theorized to be the cause of many physical dysfunctions in mammals, including common diseases like cancer and epilepsy and mental conditions such as depression and social anxiety.
“Patients who, for whatever reason, are not producing enough anandamide or 2-AG can gain homeostasis by supplementing their ECS with cannabinoids from cannabis, such as THC and CBD.”
CEDS is believed by many researchers and medical professionals to be responsible for a range of diseases and conditions that includes fibromyalgia, irritable bowel syndrome, chronic insomnia, and arthritis, to list only a few. Patients who, for whatever reason, are not producing enough anandamide or 2-AG can gain homeostasis by supplementing their ECS with cannabinoids from cannabis. Theories behind the causes of CEDS include pollution/toxification, lack of exercise, poor diet, and genetic mutations.
(It should be noted that a family of similar cannabis-derived molecules called terpenes also interacts with the ECS and is believed to offer as much health benefit to humans as cannabinoids. While beyond the scope of this article, the nuanced interaction between cannabinoids and terpenes in the ECS is called the entourage effect.)
Cause of Psychoactivity
The psychoactive effect (euphoria) of cannabis is the result of THC molecules filling the CB1 receptors within the brain. This mechanism reflects a rare proverbial hall pass. The blood/brain barrier is an extremely selective and discerning gatekeeping mechanism due to its role of protecting the brain at all costs; it allows very few molecules to pass onto the inner sanctum of the brain. Likewise, THC’s non-psychoactive cousin, CBD, can reduce systemic inflammation by attaching to the CB2 receptors of the immune system, where it exhibits the greatest binding affinity.
Build Upon Your Knowledge
Patients who possess a solid understanding of the basic interaction of the ECS and phytocannabinoids can build upon their knowledge by applying it to more advanced topics. These include the efficacy of different cannabinoids and cannabinoid profiles found in particular strains of cannabis in the treatment of common diseases, disorders, and conditions.