The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

Cannabis sativa (also known as marijuana) has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20^th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ⁹-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB₁) was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB₂). Since the 19^th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome.

The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB₁ receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.