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The endocannabinoid system

The endocannabinoid system, present in humans and other mammals, was discovered thanks to research carried out on delta-9-tetrahydrocannabinol (THC), the main active component of cannabis. Around the 1990s, two new neurotransmitters were discovered, called “endogenous cannabinoids” or “endocannabinoids”, molecules that bind to the same brain receptors that are sensitive to THC. These lipid molecules are: anandamide (AEA) and 2-arachidonylglycerol, abbreviated with the acronym of “2-AG”. These molecules are synthesized as needed and have a local effect and a short duration of action, as they are rapidly degraded by specific enzymes.

Receptors and physiological functions

Cannabinoid receptors are present throughout the body and when stimulated by endogenous cannabinoids or those present in cannabis (phytocannabinoids), they initiate a series of physiological processes.
The two main receptors are CB1 and CB2: the former is present in the central (brain) and peripheral (nerves) nervous systems and to a lesser extent in the heart, lungs, genital organs, bone marrow, thymus, uterus and immune cells. CB2 are present on cells of the immune system, spleen, bones, while in the central nervous system they are located in the spinal cord. The breadth of effects and functions includes pain modulation, inflammation, glucose metabolism, appetite, gastrointestinal motility, sleep cycle, immune response, mood, sexual libido, etc.
The action of this system also extends throughout the reproductive process: from spermatogenesis to fertilization, in fetal development and even in the development of the newborn. Cannabinoids have also been identified in breast milk, with an importance for the regulation of appetite and food assimilation, thus ensuring infant survival.
In the late 1990s, scientists discovered that the endocannabinoid system network also regulates neurogenesis in adults, that is, the growth of brain cells, as well as the migration of stem cells. It has also been found that high levels of endocannabinoids are produced and released in the brain following strokes and other traumas, which are therefore associated with neuroprotective properties.
The immune system is activated very intensely when a fever is necessary to fight a virus or bacterial infection; once the external pathogen has been fought, the endocannabinoid system lowers the fever and restores the balance of the immune system. Endocannabinoids are therefore anti-inflammatory and immunomodulatory, but if the signaling circuit is impaired and the immune system overreacts to stress then the basis for the development of an autoimmune disease or chronic inflammatory disease is created. In fact, a reduction in the number of cannabinoid receptors and / or a decrease in AEA and / or 2-AG concentrations can result in an “endocannabinoid deficiency”, which leads to a low or absent ability to adapt to chronic stress and it can be the consequence of a poor diet, lack of exercise, toxins and pollutants of the environment or genetic factors.


At the basis of scientific research on cannabis is the ability of phytocannabinoids to interact with this large system in acute and chronic pathological conditions. More than 100 cannabinoids have been identified in cannabis, but the two most studied are THC and CBD. The expression of cannabinoids is different in different cannabis varieties and generally only three or four cannabinoids are found in concentrations above 0.1%.
THC is primarily responsible for the pharmacological effects of cannabis, including its psychoactive properties, although other compounds of the plant contribute to these effects (minor cannabinoids and terpenes). THC is a CB1 and CB2 agonist, which means that it binds to cannabinoid receptors mimicking the function and role of endocannabinoids. On the other hand, CBD generally acts as a CB1 and CB2 antagonist, blocking cannabinoid receptors rather than activating them: this is why CBD is also studied to counteract some of the effects produced by THC.

Other terms to know

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