Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System

Abstract

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. From a phylogenetic point of view, the human co-evolution between the endocannabinoid system and dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a “clinical endocannabinoid deficiency syndrome”. This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm.

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

“…The altered expression of endocannabinoids and cannabinoid receptors has been observed in neurodegenerative conditions ( Table 1 ). Accordingly, it has been assumed that endocannabinoid-degradative enzymes, CB1 and CB2 receptors, and the modulation of the activity of endogenous cannabinoids represent valuable therapeutic targets in neurodegenerative diseases, as well as in other diseases such as epilepsy, stroke, inflammation, multiple sclerosis, traumatic brain injuries and psychiatric illnesses [ 4 , 120 , 121 , 122 , 123 ].…”

Expanding Research on Cannabis-Based Medicines for Liver Steatosis: A Low-Risk High-Reward Way Out of the Present Deadlock?

“…Cannabis and cannabinoids must follow the same rigorous, vigilant, and objective evaluation processes as any other promising candidate treatment for hepatic steatosis. The current knowledge on the impact of nutrition and physical activity on the ECS 9 , 70 , 71 encourages combining cannabis-based medicines and lifestyle changes into comprehensive patient-centered approaches to ensure improvements not only on clinical outcomes but also in quality of life in people at risk of advanced stages of liver disease.…”

In vitro study of the blood–brain barrier transport of bioactives from Mediterranean foods

“…5,6 In this regard, the Mediterranean diet (MD) has been proposed as a healthy dietary pattern with increasing evidence supporting its beneficial effects towards age-related pathologies, including neurodegenerative disorders and cognitive dysfunctions like AD and PD. [7][8][9] This potential of MD has been mainly related to its high content in plant foods such as fruits, vegetables, and olive oil, which are sources of an array of bioactive compounds. [10][11][12] Hydroxytyrosol (HT) and tyrosol (TYRS) are the major phenolic compounds present in virgin olive oil (VOO) (0.39-41 mg kg −1 and 0.2-32.9 mg kg −1 , respectively), and table olives (14.5-3833 mg kg −1 and 0.435-353.5 mg kg −1 , respectively).…”