Hostname: page-component-6bf8c574d5-vmclg Total loading time: 0 Render date: 2025-02-19T23:25:56.365Z Has data issue: false hasContentIssue false
  • English
  • Français

The cannabinoid system: a role in both the homeostatic and hedonic control of eating?

Published online by Cambridge University Press:  09 March 2007

Joanne A. Harrold  and
Gareth Williams
Joanne A. Harrold*
Affiliation:
Neuroendocrine and Obesity Biology Unit, Department of Medicine, University of Liverpool, University Clinical Departments, Liverpool L69 3GA, UK
Gareth Williams
Affiliation:
Neuroendocrine and Obesity Biology Unit, Department of Medicine, University of Liverpool, University Clinical Departments, Liverpool L69 3GA, UK
*
*Corresponding author: Dr Joanne A. Harrold, fax +44 151 706 5797, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Knowledge of the cannabinoid system and its components has expanded greatly over the past decade. There is increasing evidence for its role in the regulation of food intake and appetite. Cannabinoid system activity in the hypothalamus is thought to contribute to the homeostatic regulation of energy balance, under the control of the hormone leptin. A second component of cannabinoid-mediated food intake appears to involve reward pathways and the hedonic aspect of eating. With the cannabinoid system contributing to both regulatory pathways, it presents an attractive therapeutic target for the treatment of both obesity and eating disorders.

Keywords

AnandamideEndocannabinoids2-Arachidonoyl glycerolSR 141716Food intakeObesityReward
Type
Horizons in Nutritional Science
Information
British Journal of Nutrition , Volume 90 , Issue 4 , October 2003 , pp. 729 - 734
Copyright
Copyright © The Nutrition Society 2003

References

Adams, IB, Compton, DR & Martin, BR (1998) Assessment of anandamide interaction with the cannabinoid brain receptor: SR 141716A antagonism studies in mice and autoradiographic analysis of receptor binding in ratbrain. J Pharmacol Exp Ther 284, 1209–1217.Google Scholar
Arnone, M, Maruani, J, Chaperon, F, et al. (1997) Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 132, 104–106.CrossRefGoogle ScholarPubMed
Ben-Shabat, S, Fride, E, Sheskin, T, et al. (1998) An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 353, 23–31.CrossRefGoogle ScholarPubMed
Bensaid, M, Gary-Bobo, M, Esclangon, A, et al. (2003) The cannabinoid CB1 receptor agonist SR 141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 63, 908–914.CrossRefGoogle Scholar
Berger, A, Crozier, G, Bisogno, T, Cavaliere, P, Innis, S & Di, Marzo V (2001) Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brains levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci USA 98, 6402–6406.CrossRefGoogle ScholarPubMed
Boger, DL, Sato, H, Lerner, AE, Guan, X & Gilula, NB (1999) Arachidonic acid amide inhibitors of gap junction cell–cell communication. Bioorg Med Chem Lett 9, 1151–1154.CrossRefGoogle ScholarPubMed
Boger, DL, Sato, H, Lerner, AE, et al. (2000) Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide. Proc Natl Acad Sci USA 97, 5044–5049.CrossRefGoogle ScholarPubMed
Breivogel, CS, Sims, LJ & Childers, SR (1997) Regional differences in cannabinoid receptor/G-protein coupling in rat brain. J Pharmacol Exp Ther 282, 1632–1642.Google ScholarPubMed
Calignano, A, La Rana, G, Makriyannis, A, Lin, SY, Beltramo, M & Piomelli, D (1997) Inhibition of intestinal motility by anandamide, an endogenous cannabinoid. Eur J Pharmacol 340, R7–R8.Google ScholarPubMed
Colombo, G, Agabio, R, Diaz, G, Lobina, C, Reali, R & Gessa, GL (1998) Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci 63, 113–117.CrossRefGoogle ScholarPubMed
Corp, ES, Melville, LD, Greenberg, D, Gibbs, J & Smith, GP (1990) Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors. Am J Physiol 259, R317–R323.Google ScholarPubMed
Cravatt, BF, Demarest, K, Patricelli, MP, et al. (2001) Supersensitivity to anandamide and enhanced cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98, 9371–9376.CrossRefGoogle ScholarPubMed
Croci, T, Manara, L, Aureggi, G, et al. (1998) In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum. Br J Pharmacol 125, 1393–1395.CrossRefGoogle ScholarPubMed
Day, TA, Rakhshan, F, Deutsch, DG & Barker, EL (2001) Role of fatty acid amidehydrolase in the transport of the endogenous cannabinoid anandamide. Mol Pharmacol 59, 1369–1375.CrossRefGoogle Scholar
Devane, WA, Hanus, L, Breuer, A, et al. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949.CrossRefGoogle Scholar
Di Marzo, V, Goparaju, SK, Wang, L, et al. (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822–825.CrossRefGoogle ScholarPubMed
Di Lohman, wV, Melck, D, Bisogno, T & De Petrocellis, L (1998 a) Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 21, 521–528.Google Scholar
Di Marzo, V, Sepe, N, De Petrocellis, L, et al. (1998 b) Trick or treat from endocannabinoids. Nature 396, 636–637.CrossRefGoogle ScholarPubMed
Finkelstein, DI, Reeves, AK & Horne, MK (1996) An electron microscopic tracer study of the projections from the entopeduncular nucleus to the ventrolateral nucleus of the rat. Neurosci Lett 211, 33–36.CrossRefGoogle Scholar
Fulton, S, Woodside, B & Shizgal, P (2000) Modulation of brain reward circuitry by leptin. Science 287, 125–128.CrossRefGoogle ScholarPubMed
Giuffrida, A, Beltramo, M & Piomelli, D (2001) Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology. J Pharamacol Exp Ther 298, 7–14.Google Scholar
Glass, M, Dragunow, M & Faull, RLM (1997) Cannabinoid receptors in the human brain: a detailed anatomical and quantitative auto-radiographic study in the fetal, neonatal and adult human brain. Neuroscience 77, 299–318.CrossRefGoogle Scholar
Gómez, R, Navarro, M, Ferrer, B, et al. (2002) A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22, 9612–9617.CrossRefGoogle ScholarPubMed
Gorbachevskaia, AL (1999) Projections from the substantia nigra, ventral tegmental area and amygdala to the pallidium in dog brain. Morfologiia 115, 11–14.Google Scholar
Hanus, L, Abu-Lafi, S, Fride, E, et al. (2001) 2-Arachidonyl glycerol ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98, 3662–3665.CrossRefGoogle Scholar
Hao, S, Avraham, Y, Mechoulam, R & Berry, EM (2000) Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 392, 147–156.CrossRefGoogle ScholarPubMed
Harrold, JA, Elliott, JC, King, PJ, Widdowson, PS & Williams, G (2002) Down-regulation of cannabinoid-1 (CB-1) receptors in specific extrahypothalamic regions of rats with dietary obesity: a role for endogenous cannabinoids in driving appetite for palatable food? Brain Res 952, 232–238.CrossRefGoogle Scholar
Harrold, JA, Williams, G & Widdowson, PS (2000) Early leptin response to a palatable diet predicts dietary obesity in rats: key role of melanocortin-4 receptors in the ventromedial hypothalamic nucleus. J Neurochem 74, 1224–1228.CrossRefGoogle ScholarPubMed
Hohmann, AG & Herkenham, M (1999) Localization of central cannabinoid receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study. Neuroscience 90, 923–931.CrossRefGoogle ScholarPubMed
Iverson, LL (2000) The Science of Marijuana. Oxford: Oxford University Press.Google Scholar
Izzo, AA, Mascolo, N, Capasso, R, Germano, MP, De Pasquale, R & Capasso, F (1999) Inhibitory effect of cannabinoid agonists on gastric emptying in the rat. Naunyn Schmiedebergs Arch Pharamcol 360, 221–223.CrossRefGoogle ScholarPubMed
Jamshidi, N & Taylor, DA (2001) Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 134, 1151–1154.CrossRefGoogle ScholarPubMed
Kirkham, TC & Williams, CM (2001) Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology 153, 267–270.CrossRefGoogle ScholarPubMed
Kirkham, TC, Williams, CM, Fezza, F & Di Marzo, V (2002) Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 136, 550–557.CrossRefGoogle ScholarPubMed
Ledent, C, Valverde, O, Cossu, G, et al. (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283, 401–404.CrossRefGoogle ScholarPubMed
Mechoulam, R & Fride, E (2001) A hunger for cannabinoids. Nature 410, 763–764.CrossRefGoogle ScholarPubMed
Mechoulam, R, Fride, E, Hanus, L, et al. (1997) Anandamide may mediate sleep induction. Nature 389, 25–26.CrossRefGoogle ScholarPubMed
Patel, NA, Moldow, RL, Patel, JA, Wu, G & Chang, SL (1998) Arachidonylethanolamide (AEA) activation of FOS proto-oncogene protein immunoreactivity in the rat brain. Brain Res 797, 225–233.CrossRefGoogle ScholarPubMed
Pecina, S & Berridge, KC (2000) Opioid sites in nucleus accumbens shell mediate eating and hedonic ‘liking’ for food: map based on microinjection Fos plumes. Brain Res 863, 71–86.CrossRefGoogle Scholar
Rodríguez, de, Fonseca, F, Carrera, MR, Navarro, M, Koob, GF & Weiss, F (1997) Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 276, 2050–2054.CrossRefGoogle Scholar
Rodríguez, de, Fonseca, F, Navarro, M, Gómez, R, et al. (2001) An anorexic lipid mediator regulated by feeding. Nature 414, 209–212.CrossRefGoogle Scholar
Romero, J, Wenger, T, de Miguel, R, Ramos, JA & Fernandez-Ruiz, JJ (1998) Cannabinoid receptor binding did not vary in several hypothalamic nuclei after hypothalamic deafferentation. Life Sci 63, 351–356.CrossRefGoogle Scholar
Simiand, J, Keane, M, Keane, PE & Soubrié, P (1998) SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmosets. Behav Pharmacol 9, 179–181.Google Scholar
Ravinet Trillou, CR, Arnone, M, Delgorge, C, et al. (2003) Anti-obesity effect of SR 141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol 284, R345–R353.Google ScholarPubMed
Wang, L, Liu, J, Harvey-White, J, Zimmer, A & Kunos, G (2003) Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice. Proc Natl Acad Sci USA 100, 1393–1398.CrossRefGoogle ScholarPubMed
Welch, SP & Eads, M (1999) Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Res 848, 183–190.CrossRefGoogle ScholarPubMed
Welch, SP, Huffman, JW & Lowe, J (1998) Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR 141716A. J Pharmacol Exp Ther 286, 1301–1308.Google Scholar
Wenger, T, Jamali, KA, Juaneda, C, Leonardelli, J & Tramu, G (1997) Arachidonylethanolamide (anandamide) activates the parvocellular part of the hypothalamic paraventricular nucleus. Biochem Biophys Res Commun 237, 724–728.CrossRefGoogle Scholar
Widdowson, PS, Upton, R, Buckingham, R, Arch, J & Wiliams, G (1997 a) Inhibition of food response to intracerebroventricular injection of leptin is attenuated in rats with diet-induced obesity. Diabetes 46, 1782–1785.CrossRefGoogle ScholarPubMed
Widdowson, PS, Upron, R, Henderson, L, Buckingham, R, Wilson, S & Williams, G (1997 b) Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat. Brain Res 774, 1–10.CrossRefGoogle ScholarPubMed
Williams, CM & Kirkham, TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology 143, 315–317.CrossRefGoogle ScholarPubMed
Williams, CM, Rogers, PJ & Kirkham, TC (1998) Hyperphagia in pre-fed rats following oral delta 9-THC. Physiol Behav 15, 343–346.CrossRefGoogle Scholar
Willoughby, KA, Moore, SF, Martin, BR & Ellis, EF (1997) The bio-disposition and metabolism of anandamide in mice. J Pharmacol Exp Ther 282, 243–247.Google Scholar