Endocannabinoids and Energy Homeostasis

  • Stephen C. Woods
  • Daniela Cota
Part of the Contemporary Endocrinology book series (COE)


The body’s endogenous endocannabinoid system includes two endogenous agoni sts for cannabinoid-(CB)-l receptors, anadamide and 2-arachidonoyl-glycerol (2-AG). Both of these endocannabinoids (ECs) are fatty acid signals derived from cell membranes. They exert a coordinated action at multiple tissues to promote increased food intake, lipogenesis, and storage of fat. Endocannabinoids interact with multiple hypothalamic circuits and transmitter systems to stimulate food intake in general, and they also act in reward areas of the brain to selectively enhance intake of palatable foods. Activation of CB1 receptors increases enzyme activity that causes de novo fatty acids to be formed in the liver and circulating lipids to be taken up by fat cells. All these actions are reversed in animals lacking CB1 receptors, and there is growing evidence that activity of the endocannabinoid system is tonically increased in animal and human obesity. Acute or chronic administration of selective synthetic CB1 antagonists to overweight or obese individuals causes weight loss, reduced waist circumference, and an improved lipid and glycemic profile. Developing ligands for endocannabinoid receptors is an important novel therapeutic strategy for the treatment of metabolic dysregulation.

Key Words

Satiety lipogenesis obesity anandamide 2-arachidonoyl-glycerol CB1 receptors food intake leptin 


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  1. 1.
    Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci 2003;4(11):901–909.PubMedCrossRefGoogle Scholar
  2. 2.
    Matsuda LA, et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346(6284):561–564.PubMedCrossRefGoogle Scholar
  3. 3.
    Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003;4(11): 873–884.PubMedCrossRefGoogle Scholar
  4. 4.
    Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365(6441):61–65.PubMedCrossRefGoogle Scholar
  5. 5.
    Freund TF, Katonal, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003;83(3):1017–1066.PubMedGoogle Scholar
  6. 6.
    Hewlett AC, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002;54(2):161–202.CrossRefGoogle Scholar
  7. 7.
    Howlett AC, et al. Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 2004;47Supl 1:345–358.PubMedCrossRefGoogle Scholar
  8. 8.
    Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997;74(2): 129–180.PubMedCrossRefGoogle Scholar
  9. 9.
    Breivogel CS, Childers SR. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 1998;5 (6 Pt B):417–431.PubMedCrossRefGoogle Scholar
  10. 10.
    Herkenham M, et al. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991; 11(2):563–583.PubMedGoogle Scholar
  11. 11.
    Stella N. Cannabinoid signaling in glial cells. Glia 2004;48(4):267–277.PubMedCrossRefGoogle Scholar
  12. 12.
    Costa B, Colleoni M. Changes in rat brain energetic metabolism after exposure to anandamide or delta(9)-tetrahydrocannabinol. Eur J Pharmacol 2000;395(l): 1–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut 2001;48(6):859–867.PubMedCrossRefGoogle Scholar
  14. 14.
    Gomez R, et al. A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 2002;22(21):9612–9617.PubMedGoogle Scholar
  15. 15.
    Duncan M, Davison JS, Sharkey KA. Endocannabinoids and their receptors in the enteric nervous system. Aliment Pharmacol Therapeut 2005;22:667–683.CrossRefGoogle Scholar
  16. 16.
    Cota D, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 2003;112(3):423–431.PubMedCrossRefGoogle Scholar
  17. 17.
    Bensaid M, et al. The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 2003;63(4): 908–914.PubMedCrossRefGoogle Scholar
  18. 18.
    Osei-Hyiaman D, et al. Endocannabinoid activation at hepatic CB(1) receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005;115(5): 1298–1305.PubMedCrossRefGoogle Scholar
  19. 19.
    Liu YL, et al. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes Relat Metab Disord 2005;29(2): 183–187.CrossRefGoogle Scholar
  20. 20.
    Engeli S, et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005;54:2838–2843.PubMedCrossRefGoogle Scholar
  21. 21.
    Begg M, et al. Evidence for novel cannabinoid receptors. Pharmacol Therapeut 2005;106:133–145.CrossRefGoogle Scholar
  22. 22.
    Klein TW, et al. The cannabinoid system and immune modulation. J Leucocyte Biol 2003;74:486–496.CrossRefGoogle Scholar
  23. 23.
    Van Sickle MD, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005;310:329–332.PubMedCrossRefGoogle Scholar
  24. 24.
    Devane WA, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258(5090): 1946–1949.PubMedCrossRefGoogle Scholar
  25. 25.
    Mechoulam R, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50(l):83–90.PubMedCrossRefGoogle Scholar
  26. 26.
    Sugiura T, et al. Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 2002;66(2–3): 173–192.PubMedCrossRefGoogle Scholar
  27. 27.
    Bisogno T, Ligresti A, Di Marzo V. The endocannabinoid signalling system: biochemical aspects. Pharmacol Biochem Behav 2005;81:224–238.PubMedCrossRefGoogle Scholar
  28. 28.
    Di Marzo. Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004;3(9):771–784.PubMedCrossRefGoogle Scholar
  29. 29.
    Beltramo M, et al. Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 1997;277(5329): 1094–1097.PubMedCrossRefGoogle Scholar
  30. 30.
    Hillard CJ, et al. Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 1997;69:631–638.PubMedCrossRefGoogle Scholar
  31. 31.
    Hillard CJ, et al. Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J Pharmacol Exp Ther 1999;289(3): 1427–1433.PubMedGoogle Scholar
  32. 32.
    Brown SP, Brenowitz SD, Regehr WG. Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids. Nature Neurosci 2003;6:1048–1057.PubMedCrossRefGoogle Scholar
  33. 33.
    Pazos MR, et al. Functional neuroanatomy of the endocannabinoid system. Pharmacol Biochem Behav 2005;81:239–247.PubMedCrossRefGoogle Scholar
  34. 34.
    Bisogno T, et al. Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 1999;256(2):377–380.PubMedCrossRefGoogle Scholar
  35. 35.
    Bojesen IN, Hansen HS. Binding of anandamide to bovine serum albumin. J Lipid Res 2003;44(9): 1790–1794.PubMedCrossRefGoogle Scholar
  36. 36.
    Sugiura T, et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J Biol Chem 1999;274(5):2794–2801.PubMedCrossRefGoogle Scholar
  37. 37.
    Zygmunt PM, et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 1999;400:452–457.PubMedCrossRefGoogle Scholar
  38. 38.
    Katona I, et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 1999;19(11):4544–4558.PubMedGoogle Scholar
  39. 39.
    Alger BE. Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 2002;68:247–286.PubMedCrossRefGoogle Scholar
  40. 40.
    Di Marzo V, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 1994;372:686–691.PubMedCrossRefGoogle Scholar
  41. 41.
    Kim J, et al. Activation of muscarinic acetylcholine receptors enhances the release of endogenous endocannabinoids in the hippocampus. J Neurosci 2002;22:10,182-10,191.Google Scholar
  42. 42.
    Varma N, et al. Metabotropic glutamate receptors drive the endocannabinoid system in hippocampus. J Neurosci 2001;21:RC188(l-5).PubMedGoogle Scholar
  43. 43.
    Losonczy A, Biro AA, Nusser Z. Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons. Proc Natl Acad Sci USA 2004; 101:1362–1367.PubMedCrossRefGoogle Scholar
  44. 44.
    Hentges NT, Low MJ, Williams JT. Differential regulation of synaptic inputs by constitutively released endocannabinoids and exogenous cannabinoids. J Neurosci 2005;25:9746–9751.PubMedCrossRefGoogle Scholar
  45. 45.
    Xu AW, et al. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest 2005;115:951–958.PubMedCrossRefGoogle Scholar
  46. 46.
    Seeley R, et al. Melanocortin receptors in leptin effects. Nature 1997;390(Nov 27):349.Google Scholar
  47. 47.
    Di Marzo V, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001;410(6830): 822–825.PubMedCrossRefGoogle Scholar
  48. 48.
    Fagotto U, et al. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006;27:73–100.Google Scholar
  49. 49.
    Wadman M, Appetite downer awaits approval. Nature 2005;437:618–619.PubMedCrossRefGoogle Scholar
  50. 50.
    Fride E, et al. Critical role of the endogenous cannabinoid system in mouse pup suckling and growth. Eur J Pharmacol 2001;419(2–3):207–214.PubMedCrossRefGoogle Scholar
  51. 51.
    Sipe JC, et al. Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes Relat Metab Disord 2005.Google Scholar
  52. 52.
    Schwartz MW, et al. Central nervous system control of food intake. Nature 2000;404(6778):661–671.PubMedGoogle Scholar
  53. 53.
    Woods SC, et al. Signals that regulate food intake and energy homeostasis. Science 1998;280(5368): 1378–1383.PubMedCrossRefGoogle Scholar
  54. 54.
    Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004; 116:337–350.PubMedCrossRefGoogle Scholar
  55. 55.
    Woods SC, et al. Signals that regulate food intake and energy homeostasis. Science 1998;280:1378–1383.PubMedCrossRefGoogle Scholar
  56. 56.
    Gamber KM, Macarthur H, Westfall TC. Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus. Neuropharmacology 2005;49:646–652.PubMedGoogle Scholar
  57. 57.
    Hanus L, et al. Short-term fasting and prolonged semistarvation have opposite effects on 2-AG levels in mouse brain. Brain Res 2003;983(l-2): 144–151.PubMedCrossRefGoogle Scholar
  58. 58.
    Kirkham TC, et al. 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 2002; 136(4): 550–557.PubMedCrossRefGoogle Scholar
  59. 59.
    Horvath TL, Endocannabinoids and the regulation of body fat: the smoke is clearing. J Clin Invest 2003;112(3):323–326.PubMedCrossRefGoogle Scholar
  60. 60.
    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(5):487–491.PubMedCrossRefGoogle Scholar
  61. 61.
    Verty AN, McGregor IS, Mallet PE. Paraventricular hypothalamic CB(1) cannabinoid receptors are involved in the feeding stimulatory effects of Delta(9)-tetrahydrocannabinol. Neuropharmacology 2005;49:1101–1109.PubMedCrossRefGoogle Scholar
  62. 62.
    Trojniar W, Wise RA. Facilitory effect of delta 9-tetrahydrocannabinol on hypothalamically induced feeding. Psychopharmacology (Berl) 1991;103(2): 172–176.CrossRefGoogle Scholar
  63. 63.
    Jamshidi N, Taylor DA. Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 2001;134(6): 1151–1154.PubMedCrossRefGoogle Scholar
  64. 64.
    Williams CM, Kirkham TC. Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1999;143(3):315–317.CrossRefGoogle Scholar
  65. 65.
    Hao S, et al. Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2000;392(3): 147–156.PubMedCrossRefGoogle Scholar
  66. 66.
    Ravinet Trillou C, et al. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to dietinduced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004;28(4):640–648.CrossRefGoogle Scholar
  67. 67.
    Wiley JL, et al. CB1 cannabinoid receptor-mediated modulation of food intake in mice. Br J Pharmacol 2005; 145:293–300.PubMedCrossRefGoogle Scholar
  68. 68.
    Poncelet M, et al. Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neurosci Lett 2003;343(3):216–218.PubMedGoogle Scholar
  69. 69.
    Tucci SA, et al. The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. Br J Pharmacol 2004;143(5):520–523.PubMedCrossRefGoogle Scholar
  70. 70.
    Hilairet S, et al. Hypersensitization of the orexin 1 receptor by the CB1 receptor: evidence for crosstalk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 2003;278(26):23,731-23,737.CrossRefGoogle Scholar
  71. 71.
    Haj-Dahmane S, Shen RY. The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci 2005;25(4):896–905.PubMedCrossRefGoogle Scholar
  72. 72.
    Verty AN, et al. Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake. Endocrinology 2004;145(7):3224–3231.PubMedCrossRefGoogle Scholar
  73. 73.
    Berridge KC, Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 1996;20(l):1–25.PubMedCrossRefGoogle Scholar
  74. 74.
    Berthoud HR. Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 2002;26(4):393–428.PubMedCrossRefGoogle Scholar
  75. 75.
    Kelley AE, et al. Corticostriatal-hypothalamic circuitry and food motivation: Integration of energy, action and reward. Physiol Behav 2005;86:773–795.PubMedCrossRefGoogle Scholar
  76. 76.
    Abel EL, Cannabis: effects on hunger and thirst. Behav Biol 1975;15(3):255–281.PubMedCrossRefGoogle Scholar
  77. 77.
    Brown JE, Kassouny M, Cross K. Kinetic studies of food intake and sucrose solution preference by rats treated with low doses of delta9-tetrahydrocannabinol. Behav Biol 1977;20(l): 104–110.PubMedCrossRefGoogle Scholar
  78. 78.
    Williams CM, Rogers PJ, Kirkham C. Hyperphagia in pre-fed rats following oral delta9-THC. Physiol Behav 1998;65(2):343–346.PubMedCrossRefGoogle Scholar
  79. 79.
    Kirkham TC, Williams CM. Endogenous cannabinoids and appetite. Nutr Res Rev 2001; 14:65–86.CrossRefPubMedGoogle Scholar
  80. 80.
    Freedland CS, et al. Effects of SR141716A on ethanol and sucrose self-administration. Alcohol Clin Exper Res 2001;25(2):277–282.CrossRefGoogle Scholar
  81. 81.
    Gallate JE, McGregor IS. The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. Psychopharmacology (Berl) 1999;142(3):302–308.CrossRefGoogle Scholar
  82. 82.
    Simiand J, et al. SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav Pharmacol 1998;9(2): 179–181.PubMedGoogle Scholar
  83. 83.
    Colombo G, et al. Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci 1998;63(8):PL113–PL117.PubMedCrossRefGoogle Scholar
  84. 84.
    Freedland CS, Poston JS, Porrino J. Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding. Pharmacol Biochem Behav 2000;67(2):265–270.PubMedCrossRefGoogle Scholar
  85. 85.
    Harrold JA, et al. 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 2002;952(2):232–238.PubMedCrossRefGoogle Scholar
  86. 86.
    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(3):451–460.Google Scholar
  87. 87.
    Gardner EL, Vorel SR. Cannabinoid transmission and reward-related events. Neurobiol Dis 1998; 5 (6 Pt B):502–533.PubMedCrossRefGoogle Scholar
  88. 88.
    Tanda G, Goldberg SR. Cannabinoids: reward, dependence, and underlying neurochemical mechanisms— a review of recent preclinical data. Psychopharmacology (Berl) 2003 169(2): 115–134.CrossRefGoogle Scholar
  89. 89.
    Rada P, Avena NM, Hoebel BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 2005; 134:737–744.PubMedCrossRefGoogle Scholar
  90. 90.
    Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res 1995;3Suppl 4477S–4480S.Google Scholar
  91. 91.
    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(l):111–116.CrossRefGoogle Scholar
  92. 92.
    Halford JC, et al. Serotonin (5HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets 2005;6:201–213.PubMedGoogle Scholar
  93. 93.
    Fattore L, et al. Cannabinoids and reward: interactions with the opioid system. Crit Rev Neurobiol 2004;16(l-2):147–158.PubMedCrossRefGoogle Scholar
  94. 94.
    Mansour A, et al. The cloned mu, delta and kappa receptors and their endogenous ligands: evidence for two opioid peptide recognition cores. Brain Res 1995;700(l-2):89–98.PubMedCrossRefGoogle Scholar
  95. 95.
    Rodriguez JJ, Mackie K, Pickel VM. Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat caudate putamen nucleus. J Neurosci 2001;21(3):823–833.PubMedGoogle Scholar
  96. 96.
    Corchero J, et al. delta-9-Tetrahydrocannabinol increases prodynorphin and proenkephalin gene expression in the spinal cord of the rat. Life Sci 1997;61(4):PL39–PL43.CrossRefGoogle Scholar
  97. 97.
    Corchero J, Fuentes JA, Manzanares J. delta 9-Tetrahydrocannabinol increases proopiomelanocortin gene expression in the arcuate nucleus of the rat hypothalamus. Eur J Pharmacol 1997;323(2–3): 193–195.PubMedCrossRefGoogle Scholar
  98. 98.
    Vigano D, et al. Chronic morphine modulates the contents of the endocannabinoid, 2-arachidonoyl glycerol, in rat brain. Neuropsychopharmacology 2003;28(6): 1160–1167.PubMedGoogle Scholar
  99. 99.
    Corchero J, Manzanares J, Fuentes JA. Cannabinoid/opioid crosstalk in the central nervous system. Crit Rev Neurobiol 2004;16(l-2): 159–172.PubMedCrossRefGoogle Scholar
  100. 100.
    Kirkham TC, Williams CM. Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology (Berl) 2001;153(2):267–270.CrossRefGoogle Scholar
  101. 101.
    Chen RZ, et al. Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice. Brain Res 2004;999(2):227–230.PubMedCrossRefGoogle Scholar
  102. 102.
    Williams CM, Kirkham TC. Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine. Pharmacol Biochem Behav 2002;71(l-2):333–340.PubMedCrossRefGoogle Scholar
  103. 103.
    Massa F, et al. The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 2004; 113(8): 1202–1209.PubMedCrossRefGoogle Scholar
  104. 104.
    Hildebrandt AL, Kelly-Sullivan DM, Black SC. Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice. Eur J Pharmacol 2003;462(l-3): 125–132.PubMedCrossRefGoogle Scholar
  105. 105.
    Ravinet Trillou C, et al. Anti-obesity effect of SR141716, a CB 1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003;284(2):R345–R353.Google Scholar
  106. 106.
    Jbilo O, et al. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 2005; 19:1567–1569.PubMedGoogle Scholar
  107. 107.
    Poirier B, et al. The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes Metab 2005;7(l):65–72.PubMedCrossRefGoogle Scholar
  108. 108.
    Yamauchi T., et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8(11): 1288–1295.PubMedCrossRefGoogle Scholar
  109. 109.
    Moran TH, Kinzig, KP. Gastrointestinal satiety signals II. Cholecystokinin. Am J Physiol 2004;286:G183–G188.Google Scholar
  110. 110.
    Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005;128(1): 175–191.PubMedCrossRefGoogle Scholar
  111. 111.
    Woods SC. Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake. Am J Physiol 2004;286:G7–G13.Google Scholar
  112. 112.
    Burdyga G, et al. Expression of cannabinoid CB 1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 2004;24:2708–2715.PubMedCrossRefGoogle Scholar
  113. 113.
    Van Sickle MD, et ai. Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets. Am J Physiol 2003;285:G566–G576.Google Scholar
  114. 114.
    Derbenev AV, Stuart TC, Smith BN. Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve. J Physiol (Lond) 2004;559:923–938.Google Scholar
  115. 115.
    Batkai S, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 2001;7(7):827–832.PubMedCrossRefGoogle Scholar
  116. 116.
    Mukhopadhyay S, et al. The CB(1) cannabinoid receptor juxtamembrane C-terminal peptide confers activation to specific G proteins in brain. Mol Pharmacol 2000;57:162–170.PubMedGoogle Scholar
  117. 117.
    Bouaboula M, et al. A selective inverse agonist for central cannabinoid receptor inhibits mitogenactivated protein kinase activation stimulated by insulin or insuloin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 1997;272:22,330–22,339.CrossRefGoogle Scholar
  118. 118.
    Huestis MA, et al. Blockade of effects of smoked marijuana by the CBl-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 2001;58(4):322–328.PubMedCrossRefGoogle Scholar
  119. 119.
    Cleland JG, et al. Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure. Eur J Heart Fail 2004;6(4):501–508.PubMedCrossRefGoogle Scholar
  120. 120.
    Van Gaal LF, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005;365(9468): 1389–1397.PubMedCrossRefGoogle Scholar
  121. 121.
    Després JP, Golay A, Sjöström L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353:2121–2134.PubMedCrossRefGoogle Scholar
  122. 122.
    Despres JP, Lemieux I, Prud’homme D. Treatment of obesity: need to focus on high risk abdominally obese patients. Br Med J 2001;322(7288):716–720.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2007

Authors and Affiliations

  • Stephen C. Woods
    • 1
  • Daniela Cota
    • 1
  1. 1.Department of PsychiatryUniversity of Cincinnati Medical CenterCincinnati

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