Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Endogenous cannabinoid system as a modulator of food intake

International Journal of Obesity volume 27, pages 289–301 (2003)Cite this article

Abstract

The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of its main psychoactive component Δ9-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

References

  1. Yanovski SZ, Yanovski JA . Obesity. N Engl J Med 2002; 346: 591–602.

    Article  CAS  PubMed  Google Scholar 

  2. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    Article  CAS  PubMed  Google Scholar 

  3. Burstein S . Marijuana as a medicine. Nature 1997; 386: 320.

    Article  CAS  PubMed  Google Scholar 

  4. Di Marzo V, Melck D, Bisogno T, De Petrocellis L . Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998; 21: 521–528.

    Article  CAS  PubMed  Google Scholar 

  5. Abel EL . Cannabis: effects on hunger and thirst. Behav Biol 1975; 15: 255–281.

    Article  CAS  PubMed  Google Scholar 

  6. De Petrocellis L, Melck D, Bisogno T, Milone A, Di Marzo V . Finding of the endocannabinoid signalling system in Hydra, a very primitive organism: possible role in the feeding response. Neuroscience 1999; 92: 377–387.

    Article  CAS  PubMed  Google Scholar 

  7. Porter AC, Felder CC . The endocannabinoid nervous system: unique opportunities for therapeutic intervention. Pharmacol Ther 2001; 90: 45–60.

    Article  CAS  PubMed  Google Scholar 

  8. Gaoni Y, Mechoulam R . Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646.

    Article  CAS  Google Scholar 

  9. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI . Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561–564.

    Article  CAS  PubMed  Google Scholar 

  10. Munro S, Thomas KL, Abu-Shaar M . Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61–65.

    Article  CAS  PubMed  Google Scholar 

  11. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG . International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacol Rev 2002; 54: 161–202.

    Article  CAS  PubMed  Google Scholar 

  12. Schlicker E, Kathmann M . Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 2001; 22: 565–572.

    Article  CAS  PubMed  Google Scholar 

  13. Ameri A . The effects of cannabinoids on the brain. Prog Neurobiol 1999; 58: 315–348.

    Article  CAS  PubMed  Google Scholar 

  14. Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI . Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 1999; 96: 5780–5785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B . The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418: 530–534.

    Article  CAS  PubMed  Google Scholar 

  16. Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M . Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 1999; 283: 401–404.

    Article  CAS  PubMed  Google Scholar 

  17. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R . Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946–1949.

    Article  CAS  PubMed  Google Scholar 

  18. Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL . Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 1995; 48: 443–450.

    CAS  PubMed  Google Scholar 

  19. Felder CC, Nielsen A, Briley EM, Palkovits M, Priller J, Axelrod J, Nguyen DN, Richardson JM, Riggin RM, Koppel GA, Paul SM, Becker GW . Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat. FEBS Lett 1996; 393: 231–235.

    Article  CAS  PubMed  Google Scholar 

  20. Hanus L, Gopher A, Almog S, Mechoulam R . Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 1993; 36: 3032–3034.

    Article  CAS  PubMed  Google Scholar 

  21. Mechoulam R, Ben Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR . Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83–90.

    Article  CAS  PubMed  Google Scholar 

  22. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K . 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 1995; 215: 89–97.

    Article  CAS  PubMed  Google Scholar 

  23. Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R . 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 2001; 98: 3662–3665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stella N, Schweitzer P, Piomelli D . A second endogenous cannabinoid that modulates long-term potentiation. Nature 1997; 388: 773–778.

    Article  CAS  PubMed  Google Scholar 

  25. Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D . Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 1994; 372: 686–691.

    Article  CAS  PubMed  Google Scholar 

  26. Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D . Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 2002; 99: 10819–10824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mechoulam R, Feigenbaum JJ, Lander N, Segal M, Jarbe TU, Hiltunen AJ, Consroe P . Enantiomeric cannabinoids: stereospecificity of psychotropic activity. Experientia 1988; 44: 762–764.

    Article  CAS  PubMed  Google Scholar 

  28. Howlett AC, Johnson MR, Melvin LS . Classical and nonclassical cannabinoids: mechanism of action-brain binding. NIDA Res Monogr 1990; 96: 100–111.

    CAS  PubMed  Google Scholar 

  29. Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Neliat G, Caput D . SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 1994; 350: 240–244.

    Article  CAS  PubMed  Google Scholar 

  30. Lan R, Gatley J, Lu Q, Fan P, Fernando SR, Volkow ND, Pertwee R, Makriyannis A . Design and synthesis of the CB1 selective cannabinoid antagonist AM281: a potential human SPECT ligand. AAPS Pharm Sci 1999; 1: E4.

    Article  CAS  Google Scholar 

  31. Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Breliere JC, Le Fur GL . SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther 1998; 284: 644–650.

    CAS  PubMed  Google Scholar 

  32. Landsman RS, Makriyannis A, Deng H, Consroe P, Roeske WR, Yamamura HI . AM630 is an inverse agonist at the human cannabinoid CB1 receptor. Life Sci 1998; 62: L109–L113.

    Article  Google Scholar 

  33. Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D . Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 1997; 277: 1094–1097.

    Article  CAS  PubMed  Google Scholar 

  34. De Petrocellis L, Bisogno T, Davis JB, Pertwee RG, Di Marzo V . Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity. FEBS Lett 2000; 483: 52–56.

    Article  CAS  PubMed  Google Scholar 

  35. de Lago E, Fernandez-Ruiz J, Ortega-Gutierrez S, Viso A, Lopez-Rodriguez M, Ramos JA . UCM707, a potent and selective inhibitor of endocannabinoid uptake, potentiates hypokinetic and antinociceptive effects of anandamide. Eur J Pharmacol 2002; 449: 99–103.

    Article  CAS  PubMed  Google Scholar 

  36. Lutz B . Molecular biology of cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids 2002; 66: 123–142.

    Article  CAS  PubMed  Google Scholar 

  37. Murphy LL, Munoz RM, Adrian BA, Villanua MA . Function of cannabinoid receptors in the neuroendocrine regulation of hormone secretion. Neurobiol Dis 1998; 5: 432–446.

    Article  CAS  PubMed  Google Scholar 

  38. Pagotto U, Marsicano G, Fezza F, Theodoropoulou M, Grubler Y, Stalla J, Arzberger T, Milone A, Losa M, Di Marzo V, Lutz B, Stalla GK . Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level. J Clin Endocrinol Metab 2001; 86: 2687–2696.

    CAS  PubMed  Google Scholar 

  39. Navarro M, Hernandez E, Munoz RM, del Arco I, Villanua MA, Carrera MR, Rodriguez de Fonseca F . Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat. Neuroreport 1997; 8: 491–496.

    Article  CAS  PubMed  Google Scholar 

  40. Beilin M, Neumann R, Belkin M, Green K, Bar-Ilan A . Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid. J Ocul Pharmacol Ther 2000; 16: 217–230.

    Article  CAS  PubMed  Google Scholar 

  41. Calignano A, Katona I, Desarnaud F, Giuffrida A, La Rana G, Mackie K, Freund TF, Piomelli D . Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 2000; 408: 96–101.

    Article  CAS  PubMed  Google Scholar 

  42. Wagner JA, Jarai Z, Batkai S, Kunos G . Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB1 receptors. Eur J Pharmacol 2001; 423: 203–210.

    Article  CAS  PubMed  Google Scholar 

  43. Wenger T, Ledent C, Csernus V, Gerendai I . The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun 2001; 284: 363–368.

    Article  CAS  PubMed  Google Scholar 

  44. De Petrocellis L, Melck D, Bisogno T, Di Marzo V . Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders. Chem Phys Lipids 2000; 108: 191–209.

    Article  CAS  PubMed  Google Scholar 

  45. Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA . Antineoplastic activity of cannabinoids. J Natl Cancer Inst 1975; 55: 597–602.

    Article  CAS  PubMed  Google Scholar 

  46. Bifulco M, Di Marzo V . Targeting the endocannabinoid system in cancer therapy: a call for further research. Nat Med 2002; 8: 547–550.

    Article  CAS  PubMed  Google Scholar 

  47. Galve-Roperh I, Sanchez C, Cortes ML, del Pulgar TG, Izquierdo M, Guzman M . Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med 2000; 6: 313–319.

    Article  CAS  PubMed  Google Scholar 

  48. Panikashvili D, Simeonidou C, Ben Shabat S, Hanus L, Breuer A, Mechoulam R, Shohami E . An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413: 527–531.

    Article  CAS  PubMed  Google Scholar 

  49. Siler JF, Sheep WL, Bates LB, Clark GF, Cook GW, Smith WH . Marihuana smoking in Panama. Mil Surg 1933; 73: 269–280.

    Google Scholar 

  50. Tart CT . Marijuana intoxication common experiences. Nature 1970; 226: 701–704.

    Article  CAS  PubMed  Google Scholar 

  51. Haines L, Green W . Marijuana use patterns. Br J Addict Alcohol Other Drugs 1970; 65 : 347–362.

    Article  CAS  PubMed  Google Scholar 

  52. Hollister LE . Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 1971; 12: 44–49.

    Article  CAS  PubMed  Google Scholar 

  53. Abel EL . Effects of marihuana on the solution of anagrams, memory and appetite. Nature 1971; 231: 260–261.

    Article  CAS  PubMed  Google Scholar 

  54. Gagnon MA, Elie R . Effects of marijuana and D-amphetamine on the appetite, food consumption and various cardio-respiratory variables in man. Union Med Can 1975; 104: 914–921.

    CAS  PubMed  Google Scholar 

  55. Chopra RN, Chopra GS . The present position of hemp-drug addiction in India. Ind Med Res Mem 1939; 31: 1–119.

    Google Scholar 

  56. Greenberg I, Kuehnle J, Mendelson JH, Bernstein JG . Effects of marihuana use on body weight and caloric intake in humans. Psychopharmacology (Berl) 1976; 49: 79–84.

    CAS  Google Scholar 

  57. Foltin RW, Brady JV, Fischman MW . Behavioral analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 1986; 25: 577–582.

    Article  CAS  PubMed  Google Scholar 

  58. Foltin RW, Fischman MW, Byrne MF . Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 1988; 11: 1–14.

    Article  CAS  PubMed  Google Scholar 

  59. Mattes RD, Engelman K, Shaw LM, Elsohly MA . Cannabinoids and appetite stimulation. Pharmacol Biochem Behav 1994; 49: 187–195.

    Article  CAS  PubMed  Google Scholar 

  60. Kirkham TC, Williams CM . Endogenous cannabinoids and appetite. Nutr Res Rev 2001; 14: 65–86.

    Article  CAS  PubMed  Google Scholar 

  61. Williams CM, Kirkham TC . Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1999; 143: 315–317.

    Article  CAS  Google Scholar 

  62. Koch JE . Delta(9)-THC stimulates food intake in Lewis rats: effects on chow, high-fat and sweet high-fat diets. Pharmacol Biochem Behav 2001; 68: 539–543.

    Article  CAS  PubMed  Google Scholar 

  63. Gorter RW . Cancer cachexia and cannabinoids. Forsch Komplementarmed 1999; 6 (Suppl 3): 21–22.

    PubMed  Google Scholar 

  64. Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, Morales JO, Murphy R, Powderly W, Plasse TF, Mosdell KW, Shepard KV . Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.J Pain Symptom Manage 1997; 14: 7–14.

    Article  CAS  PubMed  Google Scholar 

  65. Gralla RJ . Cannabinoids and the control of chemotherapy-induced nausea and vomiting. In: Nahas GG, Sutin KM, Harvey DJ, Agurell S (eds). Marihuana and medicine. Humana Press: Totowa, NJ; 1999. pp 599–610.

    Chapter  Google Scholar 

  66. Lanzotti VJ, Thomas DR, Boyle LE, Smith TL, Gehan EA, Samuels ML . Survival with inoperable lung cancer: an integration of prognostic variables based on simple clinical criteria. Cancer 1977; 39: 303–313.

    Article  CAS  PubMed  Google Scholar 

  67. Sallan SE, Zinberg NE, Frei III E . Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 1975; 293: 795–797.

    Article  CAS  PubMed  Google Scholar 

  68. Regelson W, Thomas DR, Boyle LE, Smith TL, Gehan EA, Samuels ML . Δ9-Tetrahydrocannabinol as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: Brande MC, Szara S (eds). The pharmacology of marijuana. Raven Press: New York; 1976. pp 763–776.

    Google Scholar 

  69. Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG . Recent clinical experience with dronabinol. Pharmacol Biochem Behav 1991; 40: 695–700.

    Article  CAS  PubMed  Google Scholar 

  70. Gorter R, Seefried M, Volberding P . Dronabinol effects on weight in patients with HIV infection. AIDS 1992; 6: 127.

    Article  CAS  PubMed  Google Scholar 

  71. Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, Ries K, Evans TG . Effect of dronabinol on nutritional status in HIV infection. Ann Pharmacother 1993; 27: 827–831.

    Article  CAS  PubMed  Google Scholar 

  72. Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV . Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995; 10: 89–97.

    Article  CAS  PubMed  Google Scholar 

  73. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ . Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry 1997; 12: 913–919.

    Article  CAS  PubMed  Google Scholar 

  74. Carlini EA, Kramer C . Effects of Cannabis sativa (marihuana) on maze performance of the rat. Psychopharmacologia 1965; 7: 175–181.

    Article  CAS  PubMed  Google Scholar 

  75. Dewey WL, Harris LS, Kennedy JS . Some pharmacological and toxicological effects of 1-trans- 8 and 1-trans- 9 -tetrahydrocannabinol in laboratory rodents. Arch Int Pharmacodyn Ther 1972; 196: 133–145.

    CAS  PubMed  Google Scholar 

  76. Thompson GR, Fleischman RW, Rosenkrantz H, Braude MC . Oral and intravenous toxicity of delta9-tetrahydrocannabinol in rhesus monkeys. Toxicol Appl Pharmacol 1974; 27: 648–665.

    Article  CAS  PubMed  Google Scholar 

  77. Manning FJ, McDonough Jr JH, Elsmore TF, Saller C, Sodetz FJ . Inhibition of normal growth by chronic administration of delta-9-tetrahydrocannabinol. Science 1971; 174: 424–426.

    Article  CAS  PubMed  Google Scholar 

  78. Sjoden PO, Jarbe TU, Henriksson BG . Influence of tetrahydrocannabinols (delta8-THC and delta9-THC) on body weight, food, and water intake in rats. Pharmacol Biochem Behav 1973; 1: 395–399.

    Article  CAS  PubMed  Google Scholar 

  79. Fernandes M, Schabarek A, Coper H, Hill R . Modification of delta9-THC-actions by cannabinol and cannabidiol in the rat. Psychopharmacologia 1974; 38: 329–338.

    Article  CAS  PubMed  Google Scholar 

  80. Sofia RD, Barry III H . Acute and chronic effects of delta9-tetrahydrocannabinol on food intake by rats. Psychopharmacologia 1974; 39: 213–222.

    Article  CAS  PubMed  Google Scholar 

  81. Brown JE, Kassouny M, Cross JK . Kinetic studies of food intake and sucrose solution preference by rats treated with low doses of delta9-tetrahydrocannabinol. Behav Biol 1977; 20: 104–110.

    Article  CAS  PubMed  Google Scholar 

  82. McLaughlin CL, Baile CA, Bender PE . Cannabinols and feeding in sheep. Psychopharmacology (Berl) 1979; 64: 321–323.

    Article  CAS  Google Scholar 

  83. Van Den Broek GW, Robertson J, Keim DA, Baile CA . Feeding and depression of abomasal secretion in sheep elicited by elfazepam and 9-aza-cannabinol. Pharmacol Biochem Behav 1979; 11: 51–56.

    Article  CAS  PubMed  Google Scholar 

  84. Williams CM, Rogers PJ, Kirkham TC . Hyperphagia in pre-fed rats following oral delta9-THC. Physiol Behav 1998; 65: 343–346.

    Article  CAS  PubMed  Google Scholar 

  85. Anderson-Baker WC, McLaughlin CL, Baile CA . Oral and hypothalamic injections of barbiturates, benzodiazepines and cannabinoids and food intake in rats. Pharmacol Biochem Behav 1979; 11: 487–491.

    Article  CAS  PubMed  Google Scholar 

  86. Trojniar W, Wise RA . Facilitory effect of delta 9-tetrahydrocannabinol on hypothalamically induced feeding. Psychopharmacology (Berl) 1991; 103: 172–176.

    Article  CAS  Google Scholar 

  87. Arnone M, Maruani J, Chaperon F, Thiebot MH, Poncelet M, Soubrie P, Le Fur G . Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid CB1 receptors. Psychopharmacology (Berl) 1997; 132: 104–106.

    Article  CAS  Google Scholar 

  88. Gallate JE, McGregor IS . The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. Psychopharmacology (Berl) 1999; 142: 302–308.

    Article  CAS  Google Scholar 

  89. Freedland CS, Sharpe AL, Samson HH, Porrino LJ . Effects of SR141716A on ethanol and sucrose self-administration. Alcohol Clin Exp Res 2001; 25: 277–282.

    Article  CAS  PubMed  Google Scholar 

  90. Simiand J, Keane M, Keane PE, Soubrie P . SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav Pharmacol 1998; 9: 179–181.

    CAS  PubMed  Google Scholar 

  91. Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL . Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci 1998; 63: L113–L117.

    Article  Google Scholar 

  92. Freedland CS, Poston JS, Porrino LJ . Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding. Pharmacol Biochem Behav 2000; 67: 265–270.

    Article  CAS  PubMed  Google Scholar 

  93. Hao S, Avraham Y, Mechoulam R, Berry EM . Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2000; 392: 147–156.

    Article  CAS  PubMed  Google Scholar 

  94. Gonzalez S, Manzanares J, Berrendero F, Wenger T, Corchero J, Bisogno T, Romero J, Fuentes JA, Di Marzo V, Ramos JA, Fernandez-Ruiz J . Identification of endocannabinoids and cannabinoid CB1 receptor mRNA in the pituitary gland. Neuroendocrinology 1999; 70: 137–145.

    Article  CAS  PubMed  Google Scholar 

  95. Jamshidi N, Taylor DA . Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 2001; 134: 1151–1154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G . Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–825.

    Article  CAS  PubMed  Google Scholar 

  97. Spanagel R, Weiss F . The dopamine hypothesis of reward: past and current status. Trends Neurosci 1999; 22: 521–527.

    Article  CAS  PubMed  Google Scholar 

  98. Gardner EL, Vorel SR . Cannabinoid transmission and reward-related events. Neurobiol Dis 1998; 5: 502–533.

    Article  CAS  PubMed  Google Scholar 

  99. Hoebel BG . Brain neurotransmitters in food and drug reward. Am J Clin Nutr 1985; 42: 1133–1150.

    Article  CAS  PubMed  Google Scholar 

  100. Breivogel CS, Childers SR . The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 1998; 5: 417–431.

    Article  CAS  PubMed  Google Scholar 

  101. Mechoulam R, Fride E . Physiology. A hunger for cannabinoids. Nature 2001; 410: 763–765.

    Article  CAS  PubMed  Google Scholar 

  102. Kunos G, Batkai S . Novel physiologic functions of endocannabinoids as revealed through the use of mutant mice. Neurochem Res 2001; 26: 1015–1021.

    Article  CAS  PubMed  Google Scholar 

  103. Erickson JC, Clegg KE, Palmiter RD . Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 1996; 381: 415–421.

    Article  CAS  PubMed  Google Scholar 

  104. Gallate JE, Saharov T, Mallet PE, McGregor IS . Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. Eur J Pharmacol 1999; 370: 233–240.

    Article  CAS  PubMed  Google Scholar 

  105. Chaperon F, Thiebot MH . Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 1999; 13: 243–281.

    Article  CAS  PubMed  Google Scholar 

  106. Bisogno T, Berrendero F, Ambrosino G, Cebeira M, Ramos JA, Fernandez-Ruiz JJ, Di Marzo V . Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 1999; 256: 377–380.

    Article  CAS  PubMed  Google Scholar 

  107. Hermann H, Marsicano G, Lutz B . Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 2002; 109: 451–460.

    Article  CAS  PubMed  Google Scholar 

  108. Glass M, Dragunow M, Faull RL . Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 1997; 77: 299–318.

    Article  CAS  PubMed  Google Scholar 

  109. Berridge KC . Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 1996; 20: 1–25.

    Article  CAS  PubMed  Google Scholar 

  110. Di Marzo V, Berrendero F, Bisogno T, Gonzalez S, Cavaliere P, Romero J, Cebeira M, Ramos JA, Fernandez-Ruiz JJ . Enhancement of anandamide formation in the limbic forebrain and reduction of endocannabinoid contents in the striatum of delta9-tetrahydrocannabinol-tolerant rats. J Neurochem 2000; 74: 1627–1635.

    Article  CAS  PubMed  Google Scholar 

  111. Vickers SP, Dourish CT, Kennett GA . Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 2001; 41: 200–209.

    Article  CAS  PubMed  Google Scholar 

  112. Rowland NE, Mukherjee M, Robertson K . Effects of the cannabinoid receptor antagonist SR 141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats. Psychopharmacology (Berl) 2001; 159: 111–116.

    Article  CAS  Google Scholar 

  113. Navarro M, Carrera MR, Fratta W, Valverde O, Cossu G, Fattore L, Chowen JA, Gomez R, del Arco I, Villanua MA, Maldonado R, Koob GF, de Fonseca FR . Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci 2001; 21: 5344–5350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Cooper SJ, Kirkham TC . Opioid mechanisms in the control of food consumption and taste preferences. In: Herz A, Akil H, Simon EJ (eds.) Handbook of experimental pharmacology. Springer-Verlag: Berlin; 1993. pp 239–263.

    Google Scholar 

  115. Kirkham TC, Williams CM . Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology (Berl) 2001; 153: 267–270.

    Article  CAS  Google Scholar 

  116. Williams CM, Kirkham TC . Reversal of Delta(9)-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine. Pharmacol Biochem Behav 2002; 71: 333–340.

    Article  CAS  PubMed  Google Scholar 

  117. Crawley JN, Corwin RL . Biological actions of cholecystokinin. Peptides 1994; 15: 731–755.

    Article  CAS  PubMed  Google Scholar 

  118. Marsicano G, Lutz B . Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 1999; 11: 4213–4225.

    Article  CAS  PubMed  Google Scholar 

  119. Wiesenfeld-Hallin Z, de Arauja LG, Alster P, Xu XJ, Hokfelt T . Cholecystokinin/opioid interactions. Brain Res 1999; 848: 78–89.

    Article  CAS  PubMed  Google Scholar 

  120. Beinfeld MC, Connolly K . Activation of CB1 cannabinoid receptors in rat hippocampal slices inhibits potassium-evoked cholecystokinin release, a possible mechanism contributing to the spatial memory defects produced by cannabinoids. Neurosci Lett 2001; 301: 69–71.

    Article  CAS  PubMed  Google Scholar 

  121. Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo L, Nava F, Fu J, Murillo-Rodriguez E, Giuffrida A, LoVerme J, Gaetani S, Kathuria S, Gall C, Piomelli D . An anorexic lipid mediator regulated by feeding. Nature 2001; 414: 209–212.

    Article  CAS  PubMed  Google Scholar 

  122. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA . Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 2001; 58: 322–328.

    Article  CAS  PubMed  Google Scholar 

  123. Dhillo WS, Bloom SR . Hypothalamic peptides as drug targets for obesity. Curr Opin Pharmacol 2001; 1: 651–655.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroendocrinology Group, Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2-10, Munich, 80804, Germany

    D Cota & G K Stalla

  2. Molecular Genetics of Behaviour Group, Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2-10, Munich, 80804, Germany

    G Marsicano & B Lutz

  3. Department of Internal Medicine and Gastroenterology, Endocrinology Unit, Center for Applied Biomedical Researches (C.R.B.A.) S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, 40138, Italy

    V Vicennati, R Pasquali & U Pagotto

Authors
  1. D Cota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Marsicano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Lutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V Vicennati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G K Stalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Pasquali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. U Pagotto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U Pagotto.

Additional information

This work was supported by a grant ‘Giovani Ricercatori’, University of Bologna and in part by Fondazione Cassa di Risparmio, Bologna, Italy.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cota, D., Marsicano, G., Lutz, B. et al. Endogenous cannabinoid system as a modulator of food intake. Int J Obes 27, 289–301 (2003). https://doi.org/10.1038/sj.ijo.0802250

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802250

Keywords

  • endocannabinoids
  • anandamide
  • obesity
  • Cannabis
  • SR141716A
  • food intake

This article is cited by

Search

Advanced search

Quick links