Endocrine Abstracts

Mankind has been aware of the appetite-stimulating properties of Cannabis sativa for many centuries. Recent research has shown that cannabinoid molecules present within the plant (e.g., Δ⁹-THC) exert their pharmacological effects by stimulating specific cannabinoid receptors that are expressed by the central nervous system and a wide range of peripheral tissues, including hepatocytes and adipocytes. These receptors are normally activated by a class of arachidonic acid-derived eicosanoid molecules that are collectively known as endogenous cannabinoids. It has been demonstrated that, like THC, ‘endocannabinoids’ (e.g., anandamide and 2-arachidonoyl glycerol) can stimulate appetite and induce eating in laboratory species. Endocannabinoid hyperphagia has been shown to involve CB1 cannabinoid receptors in brain regions classically associated with the neural regulation of eating motivation, including the nucleus accumbens and hypothalamic nuclei. Central endocannabinoid systems appear to be directly involved in the mechanisms that actively promote food seeking and the enhancement of the salience or incentive value of food stimuli. Data also indicate that endocannabinoids have functional relationships with peptide signals that have been associated with the physiological regulation of eating behaviour. Thus, blockade of CB1 receptors can prevent the orexigenic actions of the putative ‘hunger signal’ ghrelin. Additionally, feeding induced by stimulation of CB1 receptors appears to involve activation of endogenous opioid peptides which are linked to the hedonic evaluation of foods. We hypothesize that the endocannabinoids are crucial to the psychological processes that underlie the anticipation and appreciation of food. In addition, there is growing evidence for cannabinoid involvement in the regulation of energy metabolism and adipogenesis. Consequently, central and peripheral endogenous cannabinoid systems represent potentially important targets for the pharmacological treatment of disorders of appetite and body weight, including obesity and cachexia.