REVIEWSEndocannabinoids in the regulation of appetite and body weightKirkham, T. C.Author Information School of Psychology, University of Liverpool, Liverpool, England Sponsorship: The author's research is supported by the United Kingdom Biotechnology and Behavioural Sciences Research Council. Correspondence and rtequests for reprints to Professor T.C. Kirkham, School of Psychology, University of Liverpool, Eleanor Rathbone Building, Bedford Street South Liverpool, L69 7ZA, England. e-mail: [email protected] Received 13 June 2005 Accepted 26 July 2005 Behavioural Pharmacology: September 2005 - Volume 16 - Issue 5-6 - p 297-313 Buy Abstract The discovery of cannabinoid receptors, together with the development of selective cannabinoid receptor antagonists, has encouraged a resurgence of cannabinoid pharmacology. With the identification of endogenous agonists, such as anandamide, scientists have sought to uncover the biological role of endocannabinoid systems; initially guided by the long-established actions of cannabis and exogenous cannabinoids such as Δ9-tetrahydrocannabinol (THC). In particular, considerable research has examined endocannabinoid involvement in appetite, eating behaviour and body weight regulation. It is now confirmed that endocannabinoids, acting at brain CB1 cannabinoid receptors, stimulate appetite and ingestive behaviours, partly through interactions with more established orexigenic and anorexigenic signals. Key structures such as the nucleus accumbens and hypothalamic nuclei are sensitive sites for the hyperphagic actions of these substances, and endocannabinoid activity in these regions varies in relation to nutritional status and feeding expression. Behavioural studies indicate that endocannabinoids increase eating motivation by enhancing the incentive salience and hedonic evaluation of ingesta. Moreover, there is strong evidence of an endocannabinoid role in energy metabolism and fuel storage. Recent developments point to potential clinical benefits of cannabinoid receptor antagonists in the management of obesity, and of agonists in the treatment of other disorders of eating and body weight regulation. © 2005 Lippincott Williams & Wilkins, Inc.