Endocannabinoid system
In order to understand the effect of cannabinoids and other substances contained in cannabis on the human body, it is necessary to have at least basic knowledge of the functioning of the so-called endocannabinoid system. It is a receptor system that is found practically throughout the body and that has been developing for hundreds of millions of years. Its goal is to maintain balance or homeostasis in the body, and cannabinoids that interact with this system can contribute to this.
How does it work
Date endocannabinoid system in addition to signaling molecules (i.e. the body of the cannabinoids themselves, which we call endocannabinoids), it also refers to all types of receptors with which endocannabinoids interact (in addition to the most well-known CB1 and CB2, there are also GPR55, TRVP1 and many others). Furthermore, enzymes that are responsible for the formation or breakdown of endocannabinoids, as well as proteins responsible for the transfer of endocannabinoids.
The entire very complex receptor system plays a major role in a long series of basic processes, including pain perception, inflammation, the production of new neurons, influencing appetite, metabolism, intestinal motility, sleep, the influence of stress and emotions, and last but not least, the development of various addictions.
As we mentioned, the primary goal of the endocannabinoid system is to maintain a state of equilibrium, or homeostasis, and if this system is hyperactive or, on the contrary, its activity is suppressed, it can lead to the development of a whole range of health problems. For example, excessive activity can affect the manifestations of multiple sclerosis, Parkinson’s or Alzheimer’s disease or epilepsy.
Regarding, for example, the cardiovascular system, the endocannabinoid system is essential not only for its physiological functioning, but also in the pathology of related diseases. It has a great influence, for example, on the regulation of blood pressure. Furthermore, this system plays a vital role in regulating the activity of the digestive system, especially when it comes to emptying. In addition, it addresses the regulation of satiety, blood sugar levels and fat intake. We could go on like this for a very long time.
What are endocannabinoids?
At the end of the 1980s, a specific receptor was discovered in the brain of mammals to which the well-known psychoactive cannabinoid THC binds. This receptor would therefore be named cannabinoid receptor 1, hence the abbreviation CB1. It didn’t take long for another type to be identified – CB2, which is found mostly in the immune system. From this came the assumption that when the organism itself produces these cannabinoid receptors, he was also supposed to produce some substances that would bind to these receptors.
In 1992, this theory was confirmed, when a team of scientists at the Hebrew University in Jerusalem discovered and isolated a substance they called anandamide (from Sanskrit – molecule of bliss). One of the main members of this team was the world-renowned chemist from Olomouc, Lumir Hanuš. Another known endocannabinoid is 2-AG or 2-arachidonoylglycerol. He was also isolated by a team in which Lumir Hanuš played the main role, in 1995.
Endocannabinoids they have a similar structure to the most important pro-inflammatory molecules in the human body – prostaglandins. They are also of the same origin, the body produces them when necessary by converting fatty acids obtained by splitting them from cell membranes. As such, the body does not store endocannabinoids anywhere, so we find them in tissues in very low concentrations. Regarding receptors, other groups such as TRPV1, TRPV2, GPR119, GPR55 or GPR18 and others were gradually discovered.
How does cannabis fit into this?
It has long been thought that cannabinoids, especially THC, react with cannabinoid receptors by fitting into them like keys in a lock and thereby activating them. This is largely true of THC, however CBD, for example, interacts with the endocannabinoid system according to recent scientific findings through a rather long series of diverse and complicated mechanisms, which do not necessarily include receptor activation.
Very briefly, the receptor is a protein molecule with a complex three-dimensional structure. When a smaller molecule of a suitable shape binds to a certain place, it fits into it like a key in a lock and either “unlocks” it completely (full agonist), partially (partial agonist), or, on the contrary, blocks it (antagonist). Then there is the possibility that it will catch in a different place, simply put from the side, making the key either easier or more difficult to fit into the lock. Thus, it is a positive or negative allosteric modifier.
It is not yet known with certainty which of these possibilities will manifest itself when CBD comes into contact with the CB1 and CB2 receptors. In the case of CB1, it is most likely a negative allosteric modification. This could also explain why CBD is able to moderate the psychotropic effects of THC. As for the possible interaction between cannabidiol and the CB2 receptor, it is still unclear. Previously, CBD was referred to as a clear activator of CB2, and this explained its significant anti-inflammatory effect. But in the meantime, several in vitro studies have been carried out and they have shown that CB2 activation does not take place. Instead, these studies identified negative allosteric or even antagonistic activity.
It is obvious that the exact mechanisms of action of cannabinoids on the endocannabinoid system are still the subject of intense scientific interest, however, the interconnectedness of the substances contained in cannabis and the most important receptor system in the human body is now indisputable.
