Can you explain briefly what is the biological function of the endocannabinoid system (ECS) in the body, what is its therapeutic importance, and how does it differ from one person to another?

Endocannabinoid system

Over the last three decades we have accumulated a wealth of knowledge about the endocannabinoid system (ECS). However, the vast majority of these studies have been performed in mice, so there are still doubts about their degree of extrapolation to humans. CB1 and CB2 cannabinoid receptors are present not only in our species but also in all vertebrates and some of the invertebrates analyzed so far. In fact, it is believed that these receptors emerged in the evolution of animals a very long time ago, specifically some 600 million years ago

These receptors serve to control chemical communication between neurons and perhaps also between other cells in the organism.

Although they are not necessary for the survival of an organism, they do seem to be necessary for that organism to “live well”, that is, to maintain its correct functioning and restore it when there is a tendency to lose it in various diseases. In short, ECS seems to have arisen in evolution to help us relax, rest, nourish ourselves, forget the traumatic, elevate our mood (remember the term “anandamide”, i.e. “happiness amide”, coined to define the first endocannabinoid discovered) and, in general, protect us from stressful situations.

Cannabis as medicine

Cannabis has been used in medicine for millennia. However, the clinical use of its active components (cannabinoids) is today rather restricted. In some countries (e.g. the United States), THC capsules (Marinol®, Syndros®) or the synthetic cannabinoid nabilone (Cesamet®) are allowed to be prescribed to stimulate appetite and inhibit nausea and vomiting in cancer or AIDS patients treated with chemotherapeutic agents.

In other countries (e.g., those of the European Union, including Spain), a standardized botanical extract with THC/CBD in a 1:1 ratio (Sativex®) can be used for the treatment of spasticity associated with multiple sclerosis, as well as a standardized botanical extract highly enriched in CBD (Epidiolex®) for the treatment of seizures associated with some pediatric epileptic syndromes. Other therapeutic possibilities of cannabinoids are still in various stages of clinical trials. In addition, some 40 countries around the world have implemented medical cannabis dispensation programs, mainly for the palliative treatment of chronic pain and to improve the overall quality of life of patients with highly debilitating diseases.

Variable cannabinoid response

As with other drugs, there are interindividual differences in the response to cannabinoids. Some factors that appear to be involved are the varying ability to metabolize cannabinoids, different levels and distribution patterns (e.g., between activating and inhibitory neurons) of cannabinoid receptors, and the existence of genetic polymorphisms in cannabinoid receptors.

In addition, the levels of cannabinoid receptors and other elements of the ECS change in a numerous of diseases, especially in some that (a) are difficult to diagnose and treat, (b) involve comorbidity (i.e., more than one of them appears simultaneously in the same patient), and (c) are characterized by central nervous system sensitization.

Examples are fibromyalgia, migraine, post-traumatic stress disorder, severe depression, inflammatory bowel disease and various neuropathies. There is some evidence that cannabinoids could alleviate, at least in some patients, the symptoms associated with these diseases, perhaps by allowing the “normalization” of a biological hypoactivity of the ECS inherent to them. Demonstrating this concept of “clinical endocannabinoid deficiency” is a major challenge for future scientific-clinical research on cannabinoids.

Manuel Guzmán Pastor

Professor of Biochemistry and Molecular Biology 

Complutense University of Madrid