Scientific inquiry into cannabis and its constituents is what finally led to the discovery of the endocannabinoid system, and this discovery is considered the most important medical discovery of the 20th century. It is mysterious, isn’t it, that cannabis research should lead to one of the most important biological systems? In fact, the endocannabinoid system permeates the entire animal kingdom, and all vertebrates and invertebrates have an endocannabinoid system.
The way that cannabis works inside the body is a topic of interest since cannabis legalization in the USA. At the same time, it is still in its infancy, thanks to a century of prohibition. Even still, the discovery of the endocannabinoid system only happened in the 1990s. This is centuries after many of the scientific discoveries that were made about the rest of the human body. For this reason, there is still a lot that modern science doesn’t know about the endocannabinoid system and how it responds to phytocannabinoids.
In any case, the interaction between cannabis and the human body is a fine meshwork of chemical reactions and signalling. The relationship between humans and cannabis is much older than the mere 30 since science discovered and acknowledged the endocannabinoid system. Needless to say, the events that have unfolded since the discovery of the endocannabinoid system continue to illustrate the importance of this fundamental human signaling system.
What is the endocannabinoid system?
The endocannabinoid system is, at its root, a very complex signalling system between cells. The discovery of the endocannabinoid system followed research into THC, cannabis’ psychoactive cannabinoid. THC was first isolated and identified in 1964 by Raphael Mechoulam in his laboratory in Israel. The discovery of THC naturally led to curiosity about which human organ responds to it. This led to the discovery of the CB1 receptor in the 1980s, discovered by Allyn Howlett at the St Louis University.
The discovery of the CB1 receptor prompted researchers to question which endogenous human compound interacted with this receptor in the absence of THC. Finally, in the early 90s, Mechoulam and his team discovered anandamide, the first ever endogenous human cannabinoid to be identified. This piece of the puzzle confirmed that the human body contains both cannabinoid receptors and endogenous cannabinoids, and this illustrated the presence of the endocannabinoid system for the first time.
The endocannabinoid system can be considered as the “other half” of the central nervous system. While neurons store neurotransmitters in the presynaptic vesicles, endocannabinoids are created virtually on demand and are released into the extracellular space.
Virtually every human organ is dotted with cannabinoid receptors. They are primarily expressed in the central nervous system (the brain) and the organs and cells of the immune system. But they can also be found in the stomach, reproductive organs, on the skin, and in the lungs.
The endocannabinoid system’s primary function is thought to be in the maintenance of homeostasis. Its mechanisms of doing so are varied and complex. It is thought to play a role in endocrine function and hormone secretion, as well as balancing neuronal activity and responses. It plays a role in reproductive function, immunity, and gastrointestinal function. The primary outcome is to control energy balance between cells.
How cannabinoids interacts with the endocannabinoid system
The two main activities of endogenous cannabinoids are to act as agonists or antagonists of a cannabinoid receptor. This is a very basic way of explaining how phytocannabinoids such as THC or CBD might interact with human cannabinoid receptors. As a very simplistic explanation, phytocannabinoids can either agonise a receptor, and thus initiate the biological response of that receptor. Alternatively, they can antagonise, and therefore block the activity of an agonist. Finally, an inverse agonist can create the opposite biological response of that receptor.
In this way, phytocannabinoids can either “switch off” a biological response, “switch on” a biological receptor, or cause the opposite biological response of that receptor. This behavior causes a whole cascade of events to take place, causing many biological changes to take place depending on the area of the body that is affected.
When THC or CBD interacts with a CB receptor, there may be changes in neuronal responses. There may be changes in inflammation or immune function. In fact, there are many ways that phytocannabinoids affect the human body, and this is why they are so versatile as therapeutic agents.
The difference between THC and CBD
THC is cannabis’ primary psychoactive compound, and most modern breeding techniques are for maximizing THC concentration. It has a very strong affinity for both CB1 and CB2 receptors, and it is thought that its psychoactive effect is via this mechanism. CBD, on the other hand, is an antagonist of both receptors.
CBD also works in peripheral ways, because for the most part, it doesn’t have a strong affinity for CB receptors. For example, CBD deactivates enzyme, FAAH, which is responsible for the breakdown and degradation of endogenous cannabinoid, anandamide. By inhibiting the degradation of anandamide, there are increased serum levels of anandamide. This endogenous cannabinoid is responsible for many different things, one of the most important being mood.
The main differences between CBD and THC in terms of their interaction with the body is in their affinity for CB receptors. The outcome of this is different every single time, depending on the expression of CB receptors in the person and their sensitivity to the phytocannabinoid.
The concept behind Clinical Endocannabinoid Deficiency
It is still a big mystery as to why THC and CBD have some of the effects that they do. For certain conditions, cannabinoids pose a very promising treatment that has been hitherto missing from modern medicine. But this may have less to do with the activity of THC and CBD, and more to do with the specific pathology of those conditions.
Ethan Russo, cannabis researcher, coined a condition called Clinical Endocannabinoid Deficiency. According to his hypothesis, many treatment resistant human conditions are actually caused by an underlying deficiency in the endocannabinoid system. Some examples include fibromyalgia, inflammatory bowel syndrome, and migraines. Ingestion of phytocannabinoids, according to Russo, restore the deficiency and thus treat the condition.
The endocannabinoid system is an extremely complex chemical signaling system that may affect anything from immune function to reproductive function. And the pathways by which this happens is different for virtually every situation. Phytocannabinoids from the cannabis plant are external mediators of this process, and even their effects are dependent on the body chemistry of every individual.
Scientific research is only just revealing the tip of the cannabis-human interaction iceberg. We know much more about the pathways of certain pharmaceuticals than we do about a plant that has been used by humans for thousands of years. The complex activity of cannabis in the human body has been clearly illustrated by modern science, but it will be years before scientists are able to paint a complete picture of how cannabis works in the human body.