Stimulation or inhibition of the endocannabinoid system regulates many pathophysiological phenomena such as neuroinflammatory and metabolic pathologies. For this reason, the cannabinoids compounds could represent new fascinating pharmacological entities.
By Andrea Mastinu and Sara Anna Bonini
Endocannabinoids are substances produced by our body with a chemical structure very similar to that of the natural extracts from the plant Cannabis. Both the endogenous and the phytoextracted cannabinoids are able to bind to the cannabinoid receptors widely diffused in the human body.
Cannabinoid receptors present in major organs
In particular, cannabinoid receptors are found in the brain, intestines, liver, adipose tissue, spleen, tonsils and immune cells. Two different type of cannabinoid receptors exist: the so called “CB1” and the “CB2”. They are expressed in different organs and are involved in diverse physiological processes.
Interestingly, they are both involved in metabolic and neuroinflammatory pathologies. Metabolic syndrome is a complex pathology that includes several cardiometabolic diseases, insulin resistance, and obesity with accumulation of abdominal white fat. Neuroinflammation in a complex physiological process that normally initiates as a brain defence response, acting with a protective goal, but that can degenerate in a chronic immune system activation leading to a pathological state.
In a review recently published in Hormone Molecular Biology and Clinical Investigation the authors present a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. the synthesis and degradation enzymes and main receptors.
An ancient remedy
Cannabis plant extracts have been used for many medicinal and spiritual applications over the past centuries. Indeed, numerous phytocannabinoids showed several anti-inflammatory effects by modulating cannabinoids transmission. Unfortunately, compounds able to act on cannabinoid receptors, especially the CB1 receptor, often have a dangerous side effect: the psychoactive effect, that alters brain activity leading to modified perceptions, level of consciousness and behaviour. For this reason, their use as pharmacological drugs has been invalidated.
Recently, thanks to new pharmacological strategies and new selective compounds that act only on cannabinoid receptors expressed in the periphery and not in the brain, it is possible to obtain positive effects on the metabolism without modifying the central nervous system circuits responsible for psychiatric adverse reactions.
The sale of cannabis has now been legalized to adults for medicinal purposes without the requirement of a medical recommendation. For example, it has now been almost five years since the voters in Washington and Colorado chose to legalize the sale of cannabis to any adult, without requiring a medical recommendation.
Cannabinoid therapy to treat obesity
In the context of neuroinflammation, the drug has to reach the brain to solve the problem; in this case, selective compounds that act only on CB2 but not on CB1 receptors, have been developed, which makes it possible to use these compounds as therapeutic agents.
The use of cannabinoids compounds will constitute the new therapeutic horizon for both obesity and neuroinflammation.
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Andrea Mastinu, Marika Premoli, Giulia Ferrari-Toninelli, Simone Tambaro, Giuseppina Maccarinelli, Maurizio Memo, Sara Anna Bonini: Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation. 03.03.2018