The appetite-stimulating effects of the cannabis plant (Cannabis sativa) have been known since ancient times, and appear to be effected through the incentive and rewarding properties of foods. Investigations into the
biological basis of the multiple effects of cannabis have yielded important breakthroughs in recent years: the discovery of two
cannabinoid receptors in brain and peripheral organ systems, and endogenous
ligands (
endocannabinoids) for these receptors. These advances have greatly increased our understanding of how appetite is regulated through these
endocannabinoid receptor systems. The presence of
endocannabinoids in the developing brain and in maternal milk have led to evidence for a critical role for CB1 receptors in oral motor control of suckling during neonatal development. The
endocannabinoids appear to regulate energy balance and food intake at four functional levels within the brain and periphery: (i) limbic system (for hedonic evaluation of foods), (ii) hypothalamus and hindbrain (integrative functions), (iii) intestinal system, and (iv) adipose tissue. At each of these levels, the
endocannabinoid system interacts with a number of better known molecules involved in appetite and weight regulation, including
leptin,
ghrelin, and the
melanocortins. Therapeutically, appetite stimulation by
cannabinoids has been studied for several decades, particularly in relation to
cachexia and
malnutrition associated with
cancer,
acquired immunodeficiency syndrome, or
anorexia nervosa. The recent advances in
cannabinoid pharmacology may lead to improved treatments for these conditions or, conversely, for combating excessive appetite and
body weight, such as
CB1 receptor antagonists as antiobesity medications. In conclusion, the exciting progress in the understanding of how the
endocannabinoid CB receptor systems influence appetite and
body weight is stimulating the development of therapeutic orexigenic and
anorectic agents. Furthermore, the role of
cannabinoid CB1 receptor activation for milk suckling in newborns may open new doors toward understanding nonorganic
failure-to-thrive in infants, who display growth failure without known organic cause.