The Endocannabinoid System as Modulator of Exercise Benefits in Mental Health

Abstract

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 disruptions, 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 cannabinoid receptors, endogenous ligands (N-arachidonoylethanolamine [anandamide, AEA] and 2- arachidonoylglycerol [2-AG]), transporters and the enzymes involved in the biosynthesis and degradation of the AEA and 2-AG, modulate mental diseases. In this review, we discuss that the endocannabinoid 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.

Keywords: Anandamide; depression.; endocannabinoids; exercise; mental health; physical activity.

Fig. (1)

The endocannabinoid system. The drawing represents the distribution in human body of the endocannabinoid components, including the CB₁ and CB₂ cannabinoid receptors, as well as the biosynthesis and degradation enzymatic routes for arachidonoylethanolamine (anandamide, AEA) or 2-arachidonoylglycerol (2-AG) governed by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Once synthetized, AEA and 2-AG bind to the cannabinoid receptors via the involvement of membrane transporter (for AEA, anandamide membrane transporter [AMT]). As shown, the presence of the cannabinoid receptors in multiple physiological systems such as brain, lung, gastrointestinal tract, etc. (Panel A) suggest the modulatory role of both receptors in the control of a diversity of complex functions, including memory and learning, brain plasticity, neuronal development, stress and emotions, among many others (Panel B). In addition, the image illustrates that arachidonic acid-containing diacylglycerol (DAG), diacylglycerol lipase (DAGL) synthesizes 2-AG whereas NAPE (N-arachidonoyl phosphatidylethanolamine) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) participates in the formation of AEA. Once released, both lipids (2-AG and AEA) bind and activate the cannabinoid receptors, which in turn, promotes calcium (Ca²⁺) influx and potassium (K⁺) efflux for modulating neurotransmission (Panel C). (A higher resolution/colour version of this figure is available in the electronic copy of the article).

Fig. (2)

The benefits of physical exercise benefits in endocannabinoid system and mental health. The positive effects of physical exercise on boosting the endocannabinoid system activity for modulating the mental health functioning. Current evidence has shown that exercise increases the activity of the endocannabinoids by presumably inducing an “euphoric-like” effect. In addition, practicing exercise controls mental health symptomatology. However, further studies are needed to describe the mechanism of action that engages the increase in the contents of the endocannabinoids and the control of mental health disruptions. (A higher resolution/colour version of this figure is available in the electronic copy of the article).