The endocannabinoid system as modulator of exercise benefits in mental health

According to the World Health Organization (WHO), 47 million people display mental health disorders Worldwide. In addition, epidemiological studies have shown that the extension of life expectancy and the increase in aged population will significantly impact the prevalence of several mental impairments. Although there are strategies for preventing and alleviating mental illnesses, such as pharmacological and psychological approaches, limited results have been observed. Thus, the search for new therapeutics for managing psychiatric disorders has explored multiple roads. In recent years, it has been demonstrated that physical activity and exercise promote health benefits. On the other hand, among the neurobiological systems that participate in the genesis and development of mental disrup-tions, the endocannabinoid system has been suggested as an active player. Supporting this hypothesis, data suggest that the elements comprising the endocannabinoid system, such as the CB₁/CB₂ canna-binoid receptors, endogenous ligands (N-arachidonoylethanolamine [anandamide, AEA] and 2-arachidonoylglycerol [2-AG]), transporters and the enzymes involved in the biosynthesis and degrada-tion of the AEA and 2-AG, modulate mental diseases. In this review, we discuss that the endocanna-binoid system might be considered as a modulator for the positive outcomes of exercise in the management of mental disorders. Clinically, this promising field might be exploited by targeting the elements of the endocannabinoid system aimed to increase the exercise benefits applied to patients with mental illnesses.