Molecular Neurobiology

, Volume 36, Issue 1, pp 113–128 | Cite as

Cannabinoids in Eating Disorders and Obesity

Article

Abstract

Cannabinoid system is a crucial mechanism in regulating food intake and energy metabolism. It is involved in central and peripheral mechanisms regulating such behavior, interacting with many other signaling systems with a role in metabolic regulation. Cannabinoid agonists promote food intake, and soon a cannabinoid antagonist, rimonabant, will be marketed for the treatment of obesity. It not only causes weight loss, but also alleviates metabolic syndrome. We present a review of current knowledge on this subject, along with data from our own research: genetic studies on this system in eating disorders and obesity and studies locating cannabinoid receptors in areas related to food intake. Such studies suggest cannabinoid hyperactivity in obesity, and this excessive activity may have prognostic implications.

Keywords

Cannabinoid system Obesity Eating disorders Food intake Energy metabolism 

Abbreviations

AgRP

agouti-related protein

AEA

anandamide

2-AG

2-arachidonoyl-glycerol

ARC

arcuate hypothalamic nucleus

BBB

blood–brain barrier

BMI

body mass index

BDNF

brain-derived neurotrophic factor

CB1

cannabinoid receptor type 1

CCK

cholecystokinin

CART

cocaine- and amphetamine-regulated transcript

CRH

corticotropin-releasing hormone

DIO

diet-induced obesity

DMH

dorsomedial hypothalamic nucleus

ED

eating disorders

ECS

endocannabinoid system

FAAH

fatty-acid amide hydrolase

FAS

fatty-acid synthase

GHS-R

ghrelin receptor

GAPDH

glyceraldehyde-3-phosphate dehydrogenase

HDL

high-density lipoprotein

HPA

hypothalamic–pituitary–adrenal axis

KO

knockout

LHN

lateral hypothalamic nucleus

MAP-kinase

mitogen-activated protein kinase

MCH

melanine concentrating hormone

α-MSH

melanocyte stimulating hormone

NPY

neuropeptide Y

Nac

nucleus accumbens

NTS

nucleus of the tractus solitarius

OEA

oleoyl-ethanolamide

PVN

paraventricular nucleus

PYY

peptide YY

POMC

pro-opiomelanocortin

RIO

Rimonabant in Obesity clinical trials

SREBP-1c

sterol response element-binding protein 1c

STRATUS

Studies with Rimonabant and Tobacco Use

THC

tetrahydrocannabinol

TRH

thyrotropin-releasing hormone

VTA

ventral tegmental area

VMH

ventromedial hypothalamic nucleus

References

  1. 1.
    Grinspoon L, Bakalar JB (1993) Marihuana. The forbidden medicine. Yale University Press, LondonGoogle Scholar
  2. 2.
    Ramos JA, Fernández J (2000) Uso de los cannabinoides a través de la historia. Adicciones 12(suppl 2):19–30Google Scholar
  3. 3.
    Hollister L (2001) Marijuana (cannabis) as medicine. Journal of Cannabis Therapeutics 1:5–28Google Scholar
  4. 4.
    Di Marzo V, Sepe N, De Petrocellis L, Berger A, Crozier G, Fride E, Mechoulam R (1998) Trick or treat from food endocannabinoids?. Nature 396:636–637 (letter)PubMedGoogle Scholar
  5. 5.
    Anand BK, Brobeck JR (1951) Localization of a feeding center in the hypothalamus of the rat. Proc Soc Exp Biol Med 77:323–324PubMedGoogle Scholar
  6. 6.
    Berthoud HR (2002) Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 26:393–428PubMedGoogle Scholar
  7. 7.
    Broberger C (2005) Brain regulation of food intake and appetite: molecules and networks. J Intern Med 258:301–327PubMedGoogle Scholar
  8. 8.
    Wynne K, Stanley S, McGowan B, Bloom S (2005) Appetite control. J Endocrinol 184:291–318PubMedGoogle Scholar
  9. 9.
    Abizaid A, Gao Q, Horvath TL (2006) Thoughts for food: brain mechanisms and peripheral energy balance. Neuron 51:691–702PubMedGoogle Scholar
  10. 10.
    Breivogel CS, Childers SR (1998) The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 5:417–431PubMedGoogle Scholar
  11. 11.
    Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289–295PubMedGoogle Scholar
  12. 12.
    Smith GP (1999) Introduction to the reviews on peptides and the control of food intake and body weight. Neuropeptides 33:323–328PubMedGoogle Scholar
  13. 13.
    Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ (2005) Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310:996–999PubMedGoogle Scholar
  14. 14.
    Halford JC, Blundell JE (2000) Pharmacology of appetite suppression. Prog Drug Res 54:25–58PubMedGoogle Scholar
  15. 15.
    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 392:147–156PubMedGoogle Scholar
  16. 16.
    Martinez-Gonzalez D, Bonilla-Jaime H, Morales-Otal A, Henriksen SJ, Velazquez-Moctezuma J, Prospero-Garcia O (2004) Oleamide and anandamide effects on food intake and sexual behavior of rats. Neurosci Lett 364:1–6PubMedGoogle Scholar
  17. 17.
    Wiley JL, Burston JJ, Leggett DC, Alekseeva OO, Razdan RK, Mahadevan A, Martin BR (2005) CB1 cannabinoid receptor-mediated modulation of food intake in mice. Br J Pharmacol 145:293–300PubMedGoogle Scholar
  18. 18.
    Williams CM, Rogers PJ, Kirkham TC (1998) Hyperphagia in pre-fed rats following oral delta9-THC. Physiol Behav 65:343–346PubMedGoogle Scholar
  19. 19.
    Williams CM, Kirkham TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology 143:315–317PubMedGoogle Scholar
  20. 20.
    Williams CM, Kirkham TC (2002) Observational analysis of feeding induced by delta9-THC and anandamide. Physiol Behav 76:241–250PubMedGoogle Scholar
  21. 21.
    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 136:550–557PubMedGoogle Scholar
  22. 22.
    Avraham Y, Menachem AB, Okun A, Zlotarav O, Abel N, Mechoulam R, et al (2005) Effects of the endocannabinoid noladin ether on body weight, food consumption, locomotor activity, and cognitive index in mice. Brain Res Bull 65:117–123PubMedGoogle Scholar
  23. 23.
    Avraham Y, Ben-Shushan D, Breuer A, Zolotarev O, Okon A, Fink N et al (2004) Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss. Pharmacol Biochem Behav 77:675–684PubMedGoogle Scholar
  24. 24.
    Jamshidi N, Taylor DA (2001) Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 134:1151–1154PubMedGoogle Scholar
  25. 25.
    Miller CC, Murray TF, Freeman KG, Edwards GL (2004) Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain. Physiol Behav 80:611–616PubMedGoogle Scholar
  26. 26.
    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:PL113–117PubMedGoogle Scholar
  27. 27.
    Freedland CS, Poston JS, Porrino LJ (2000) Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding. Pharmacol Biochem Behav 67:265–270PubMedGoogle Scholar
  28. 28.
    Simiand J, Keane M, Keane PE, Soubrie P (1998) SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav Pharmacol 9:179–181PubMedGoogle Scholar
  29. 29.
    Gomez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, et al (2002) A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22:9612–9617PubMedGoogle Scholar
  30. 30.
    Rowland NE, Mukherjee M, Robertson K (2001) Effects of the cannabinoid receptor antagonist SR141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats. Psychopharmacology 159:111–116PubMedGoogle Scholar
  31. 31.
    Koch JF, Werner NA (2000) Effects of the cannabinoid antagonists AM 630 and AM 281 on deprivation-induced food intake in Lewis rats. Soc Neurosci 26:569 (Abst)Google Scholar
  32. 32.
    Pagotto U, Pasquali R (2006) Endocannabinoids and energy metabolism. J Endocrinol Investig 29(suppl):66–76Google Scholar
  33. 33.
    Arnone M, Maruani J, Chaperon F, Thiebot MH, Poncelet M, Soubrie P, Le Fur G (1997) Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 132:104–106PubMedGoogle Scholar
  34. 34.
    Ward SJ, Dykstra LA (2005) The role of CB1 receptors in sweet versus fat reinforcement: effect of CB1 receptor deletion, CB1 receptor antagonism (SR141716A) and CB1 receptor agonism (CP-55940). Behav Pharmacol 16:381–388PubMedGoogle Scholar
  35. 35.
    Joppa MA, Markison S, Gogas KR, Foster AC, Naeve GS (2002) The cannabinoid antagonist SR141716 inhibits food intake in mice but does not decrease activity. In: Proceedings of the 12th annual symposium on the cannabinoids. ICRS; USAGoogle Scholar
  36. 36.
    McLaughlin PJ, Winston K, Swezey L, Wisniecki A, Aberman J, Tardif DJ, et al (2003) The cannabinoid CB1 antagonists SR 141716A and AM 251 suppress food intake and food-reinforced behavior in a variety of tasks in rats. Behav Pharmacol 14:583–588PubMedGoogle Scholar
  37. 37.
    Verty AN, McGregor IS, Mallet PE (2004) Consumption of high carbohydrate, high fat, and normal chow is equally suppressed by a cannabinoid receptor antagonist in non-deprived rats. Neurosci Lett 354:217–220PubMedGoogle Scholar
  38. 38.
    Bensaid M, Gary-Bobo M, Esclangon A, Maffrand JP, Le Fur G, Oury-Donat F et al (2003) 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 63:908–914PubMedGoogle Scholar
  39. 39.
    Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP et al (2003) Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 284:R345–353PubMedGoogle Scholar
  40. 40.
    Vickers SP, Webster LJ, Wyatt A, Dourish CT, Kennett GA (2003) Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats. Psychopharmacology 167:103–111PubMedGoogle Scholar
  41. 41.
    Gessa GL, Orru A, Lai P, Maccioni P, Lecca R, Lobina C et al (2006) Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats. Psychopharmacology 185:248–254PubMedGoogle Scholar
  42. 42.
    Black SC, Hildebrandt AL, Kelly-Sullivan DM (2002) Determination of CB1 receptor antagonist anorectic efficacy vs adipose tissue mass reduction. In: Proceedings of the 12th annual symposium on the cannabinoids. ICRS; USAGoogle Scholar
  43. 43.
    Chambers AP, Sharkey KA, Koopmans HS (2004) Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of daily food intake in the rat. Physiol Behav 82:863–869PubMedGoogle Scholar
  44. 44.
    Hildebrandt AL, Kelly-Sullivan DM, Black SC (2003) Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice. Eur J Pharmacol 462:125–132PubMedGoogle Scholar
  45. 45.
    Ravinet Trillou C, Delgorge C, Menet C, Arnone M, Soubrie P (2004) CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 28:640–648PubMedGoogle Scholar
  46. 46.
    Tart CT (1970) Marijuana intoxication common experiences. Nature 226:701–704PubMedGoogle Scholar
  47. 47.
    Hollister LE (1971) Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 12:44–49PubMedGoogle Scholar
  48. 48.
    Abel EL (1971) Effects of marihuana on the solution of anagrams, memory and appetite. Nature 231:260–261PubMedGoogle Scholar
  49. 49.
    Greenberg I, Kuehnle J, Mendelson JH, Bernstein JG (1976) Effects of marihuana use on body weight and caloric intake in humans. Psychopharmacology 49:79–84PubMedGoogle Scholar
  50. 50.
    Foltin RW, Brady JV, Fischman MW (1986) Behavioral analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 25:577–582PubMedGoogle Scholar
  51. 51.
    Foltin RW, Fischman MW, Byrne MF (1988) Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 11:1–14PubMedGoogle Scholar
  52. 52.
    Mattes RD, Engelman K, Shaw LM, Elsohly MA (1994) Cannabinoids and appetite stimulation. Pharmacol Biochem Behav 49:187–195PubMedGoogle Scholar
  53. 53.
    Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT et al (2003) Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med 139:258–266PubMedGoogle Scholar
  54. 54.
    Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B et al (1997) Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage 14:7–14PubMedGoogle Scholar
  55. 55.
    Haney M, Rabkin J, Gunderson E, Foltin RW (2005) Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology 181:170–178PubMedGoogle Scholar
  56. 56.
    Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA et al (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 20:567–573PubMedGoogle Scholar
  57. 57.
    Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ (1997) Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 12:913–919PubMedGoogle Scholar
  58. 58.
    Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999) Abstinence symptoms following smoked marijuana in humans. Psychopharmacology 141:395–404PubMedGoogle Scholar
  59. 59.
    Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999) Abstinence symptoms following oral THC administration to humans. Psychopharmacology 141:385–394PubMedGoogle Scholar
  60. 60.
    Budney AJ, Hughes JR, Moore BA, Vandrey R (2004) Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry 161:1967–1977PubMedGoogle Scholar
  61. 61.
    Cooper SJ (2004) Endocannabinoids and food consumption: comparisons with benzodiazepine and opioid palatability-dependent appetite. Eur J Pharmacol 500:37–49PubMedGoogle Scholar
  62. 62.
    Romero J, Wenger T, De Miguel R, Ramos JA, Fernández-Ruiz JJ (1998) Cannabinoid receptor binding did not vary in several hypothalamic nuclei after hypothalamic deafferentation. Life Sci 63:351–356PubMedGoogle Scholar
  63. 63.
    Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583PubMedGoogle Scholar
  64. 64.
    Derbenev AV, Stuart TC, Smith BN (2004) Cannabinoids suppress synaptic input to neurones of the rat dorsal motor nucleus of the vagus nerve. J Physiol 559:923–938PubMedGoogle Scholar
  65. 65.
    Cota D, Marsicano G, Tschop M, Grubler Y, Flachskamm C, Schubert M et al (2003) The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 112:423–431PubMedGoogle Scholar
  66. 66.
    Pagotto U, Vicennati V, Pasquali R (2005) The endocannabinoid system and the treatment of obesity. Ann Med 37:270–275PubMedGoogle Scholar
  67. 67.
    Jo YH, Chen YJ, Chua SC Jr, Talmage DA, Role LW (2005) Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Neuron 48:1055–1066PubMedGoogle Scholar
  68. 68.
    Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, et al (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410:822–825PubMedGoogle Scholar
  69. 69.
    Gamber KM, Macarthur H, Westfall TC (2005) Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus. Neuropharmacology 49:646–652PubMedGoogle Scholar
  70. 70.
    Poncelet M, Maruani J, Calassi R, Soubrie P (2003) Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neurosci Lett 343:216–218PubMedGoogle Scholar
  71. 71.
    Osei-Hyiaman D, Depetrillo M, Harvey-White J, Bannon AW, Cravatt BF, Kuhar MJ et al (2005) Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide. Neuroendocrinology 81:273–282PubMedGoogle Scholar
  72. 72.
    Solinas M, Goldberg SR (2005) Motivational effects of cannabinoids and opioids on food reinforcement depend on simultaneous activation of cannabinoid and opioid systems. Neuropsychopharmacology 30:2035–2045PubMedGoogle Scholar
  73. 73.
    Tucci SA, Rogers EK, Korbonits M, Kirkham TC (2004) The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. Br J Pharmacol 143:520–523PubMedGoogle Scholar
  74. 74.
    Cani PD, Montoya ML, Neyrinck AM, Delzenne NM, Lambert DM (2004) Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide. Br J Nutr 92:757–761PubMedGoogle Scholar
  75. 75.
    Gary-Bobo M, Elachouri G, Scatton B, Le Fur G, Oury-Donat F, Bensaid M (2006) The cannabinoid CB1 receptor antagonist rimonabant (SR141716) inhibits cell proliferation and increases markers of adipocyte maturation in cultured mouse 3T3 F442A preadipocytes. Mol Pharmacol 69:471–478PubMedGoogle Scholar
  76. 76.
    Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C et al (2006) Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 91:3171–3180PubMedGoogle Scholar
  77. 77.
    Perwitz N, Fasshauer M, Klein J (2006) Cannabinoid receptor signaling directly inhibits thermogenesis and alters expression of adiponectin and visfatin. Horm Metab Res 38:356–358PubMedGoogle Scholar
  78. 78.
    Jbilo O, Ravinet-Trillou C, Arnone M, Buisson I, Bribes E, Peleraux A, et al (2005) The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 19:1567–1569PubMedGoogle Scholar
  79. 79.
    Burdyga G, Lal S, Varro A, Dimaline R, Thompson DG, Dockray GJ (2004) Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 24:2708–2715PubMedGoogle Scholar
  80. 80.
    Verty AN, McFarlane JR, McGregor IS, Mallet PE (2004) Evidence for an interaction between CB1 cannabinoid and oxytocin receptors in food and water intake. Neuropharmacology 47:593–603PubMedGoogle Scholar
  81. 81.
    Verty AN, McFarlane JR, McGregor IS, Mallet PE (2004) Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake. Endocrinology 145:3224–3231PubMedGoogle Scholar
  82. 82.
    Hilairet S, Bouaboula M, Carriere D, Le Fur G, Casellas P (2003) Hypersensitization of the orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 278:23731–23737PubMedGoogle Scholar
  83. 83.
    Di S, Malcher-Lopes R, Halmos KC (2003) Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 23:4850–4857PubMedGoogle Scholar
  84. 84.
    Hermann H, Lutz B (2005) Coexpression of the cannabinoid receptor type 1 with the corticotropin-releasing hormone receptor type 1 in distinct regions of the adult mouse forebrain. Neurosci Lett 375:13–18PubMedGoogle Scholar
  85. 85.
    Kirkham TC (2005) Endocannabinoids in the regulation of appetite and body weight. Behav Pharmacol 16:297–313PubMedGoogle Scholar
  86. 86.
    Cota D, Tschöp MH, Horvath TL, Levine AS (2006) Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev 51:85–107PubMedGoogle Scholar
  87. 87.
    Kyrou I, Valsamakis G, Tsigos C (2006) The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome. Ann NY Acad Sci 1083:270–305PubMedGoogle Scholar
  88. 88.
    Berridge KC (1996) Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 20:1–25PubMedGoogle Scholar
  89. 89.
    Lupica CR, Riegel AC, Hoffman AF (2004) Marijuana and cannabinoid regulation of brain reward circuits. Br J Pharmacol 143:227–234PubMedGoogle Scholar
  90. 90.
    Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284PubMedGoogle Scholar
  91. 91.
    Verty AN, McGregor IS, Mallet PE (2004) The dopamine receptor antagonist SCH 23390 attenuates feeding induced by delta9-tetrahydrocannabinol. Brain Res 1020:188–195PubMedGoogle Scholar
  92. 92.
    Duarte C, Alonso R, Bichet N, Cohen C, Soubrie P, Thiebot MH (2004) Blockade by the cannabinoid CB1 receptor antagonist, rimonabant (SR141716), of the potentiation by quinelorane of food-primed reinstatement of food-seeking behavior. Neuropsychopharmacology 29:911–920PubMedGoogle Scholar
  93. 93.
    Freedland CS, Sharpe AL, Samson HH, Porrino LJ (2001) Effects of SR141716A on ethanol and sucrose self-administration. Alcohol Clin Exp Res 25:277–282PubMedGoogle Scholar
  94. 94.
    Higgs S, Williams CM, Kirkham TC (2003) Cannabinoid influences on palatability: microstructural analysis of sucrose drinking after delta(9)-tetrahydrocannabinol, anandamide, 2-arachidonoyl glycerol and SR141716. Psychopharmacology 165:370–377PubMedGoogle Scholar
  95. 95.
    Koch JE, Matthews SM (2001) Delta9-tetrahydrocannabinol stimulates palatable food intake in Lewis rats: effects of peripheral and central administration. Nutr Neurosci 4:179–187PubMedGoogle Scholar
  96. 96.
    Thornton-Jones ZD, Vickers SP, Clifton PG (2005) The cannabinoid CB1 receptor antagonist SR141716A reduces appetitive and consummatory responses for food. Psychopharmacology 179:452–460PubMedGoogle Scholar
  97. 97.
    Pavon FJ, Bilbao A, Hernandez-Folgado L, Cippitelli A, Jagerovic N, Abellan G et al (2006) Antiobesity effects of the novel in vivo neutral cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole-LH 21. Neuropharmacology 51:358–366PubMedGoogle Scholar
  98. 98.
    Burdyga G, Lal S, Varro A, Dimaline R, Thompson DG, Dockray GJ (2004) Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 24:2708–2715PubMedGoogle Scholar
  99. 99.
    Matias I, Di Marzo V (2006) Endocannabinoid synthesis and degradation, and their regulation in the framework of energy balance. J Endocrinol Investig 29:15–26Google Scholar
  100. 100.
    Pagotto U, Vicennati V, Pasquali R (2007) The endocannabinoid system in the physiopathology of metabolic disorders. Horm Res 67(suppl 1):186–190Google Scholar
  101. 101.
    Massa F, Monory K (2006) Endocannabinoids and the gastrointestinal tract. J Endocrinol Investig 29(suppl 3):47–57Google Scholar
  102. 102.
    Lichtman AH, Cravatt BF (2005) Food for thought: endocannabinoid modulation of lipogenesis. J Clin Invest 115:1130–1133PubMedGoogle Scholar
  103. 103.
    Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935PubMedGoogle Scholar
  104. 104.
    Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Batkai S, et al (2005) Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 115:1298–1305PubMedGoogle Scholar
  105. 105.
    Kola B, Hubina E, Tucci SA, Kirkham TC, Garcia EA, Mitchell SE, et al (2005) Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem 280:25196–25201PubMedGoogle Scholar
  106. 106.
    Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R (2006) The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 27:73–100PubMedGoogle Scholar
  107. 107.
    Liu YL, Connoley IP, Wilson CA, Stock MJ (2005) 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 29:183–187Google Scholar
  108. 108.
    Adami M, Frati P, Bertini S, Kulkarni-Narla A, Brown DR, de Caro G, et al (2002) Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach. Br J Pharmacol 135:1598–1606PubMedGoogle Scholar
  109. 109.
    Storr M, Gaffal E, Saur D, Schusdziarra V, Allescher HD (2002) Effect of cannabinoids on neural transmission in rat gastric fundus. Can J Physiol Pharmacol 80:67–76PubMedGoogle Scholar
  110. 110.
    Kaye WH, Devlin B, Barbarich N, Bulik CM, Thornton L, Bacanu SA, et al (2004) Genetic analysis of bulimia nervosa: methods and sample description. Int J Eat Disord 35:556–570PubMedGoogle Scholar
  111. 111.
    Kas MJ, Van Elburg AA, Van Engeland H, Adan RA (2003) Refinement of behavioural traits in animals for the genetic dissection of eating disorders. Eur J Pharmacol 480:13–20PubMedGoogle Scholar
  112. 112.
    Monteleone P, DiLieto A, Castaldo E, Maj M (2004) Leptin functioning in eating disorders. CNS Spectr 9:523–529PubMedGoogle Scholar
  113. 113.
    Monteleone P, Martiadis V, Rigamonti AE, Fabrazzo M, Giordani C, Muller EE, et al (2005) Investigation of peptide YY and ghrelin responses to a test meal in bulimia nervosa. Biol Psychiatry 57:926–931PubMedGoogle Scholar
  114. 114.
    Monteleone P, Fabrazzo M, Tortorella A, Martiadis V, Serritella C, Maj M (2005) Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa. Psychoneuroendocrinology 30:243–250PubMedGoogle Scholar
  115. 115.
    Djurovic M, Pekic S, Petakov M, Damjanovic S, Doknic M, Dieguez C, et al (2004) Gonadotropin response to clomiphene and plasma leptin levels in weight recovered but amenorrhoeic patients with anorexia nervosa. J Endocrinol Investig 27:523–527Google Scholar
  116. 116.
    Baranowska B, Wolinska-Witort E, Wasilewska-Dziubinska E, Roguski K, Chmielowska M (2001) Plasma leptin, neuropeptide Y (NPY) and galanin concentrations in bulimia nervosa and in anorexia nervosa. Neuro Endocrinol Lett 22:356–358PubMedGoogle Scholar
  117. 117.
    Housova J, Anderlova K, Krizova J, Haluzikova D, Kremen J, Kumstyrova T, et al (2005) Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab 90:1366–1370PubMedGoogle Scholar
  118. 118.
    Misra M, Miller KK, Tsai P, Gallagher K, Lin A, Lee N, et al (2006) Elevated peptide YY levels in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 91:1027–1033PubMedGoogle Scholar
  119. 119.
    Grice DE, Halmi KA, Fichter MM, Strober M, Woodside DB, Treasure JT, et al (2002) Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. Am J Hum Genet 70:787–792PubMedGoogle Scholar
  120. 120.
    Chiang KP, Gerber AL, Sipe JC, Cravatt BF (2004) Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet 13:2113–2119PubMedGoogle Scholar
  121. 121.
    Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci U S A 99:8394–8399PubMedGoogle Scholar
  122. 122.
    Cravatt BF, Lichtman AH (2002) The enzymatic inactivation of the fatty acid amide class of signaling lipids. Chem Phys Lipids 121:135–148PubMedGoogle Scholar
  123. 123.
    Arias F, Ampuero I, Sagredo O, Maestro B, Almodovar F, Sánchez S, et al (2007) Lack of association between polymorphisms in cannabinoid receptor gene (CNR1) and fatty acid amide hydroxylase gene (FAAH) and eating disorders in a preliminary study. Psychiatr Genet (in press)Google Scholar
  124. 124.
    Siegfried Z, Kanyas K, Latzer Y, Karni O, Bloch M, Lerer B, et al (2004) Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes. Am J Med Genet B Neuropsychiatr Genet 125:126–130PubMedGoogle Scholar
  125. 125.
    Monteleone P, Matias I, Martiadis V, De Petrocellis L, Maj M, Di Marzo V (2005) Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology 30:1216–1221PubMedGoogle Scholar
  126. 126.
    Gross H, Ebert MH, Faden VB, Goldberg SC, Kaye WH, Caine ED, et al (1983) A double-blind trial of delta 9-tetrahydrocannabinol in primary anorexia nervosa. J Clin Psychopharmacol 3:165–171PubMedGoogle Scholar
  127. 127.
    Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM (2004) Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 291:2847–2850PubMedGoogle Scholar
  128. 128.
    Bray GA, Paeratakul S, Popkin BM (2004) Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav 83:549–555PubMedGoogle Scholar
  129. 129.
    Marti A, Moreno-Aliaga MJ, Hebebrand J, Martinez JA (2004) Genes, lifestyles and obesity. Int J Obes Relat Metab Disord 28(suppl 3):S29–36PubMedGoogle Scholar
  130. 130.
    Bulik CM, Sullivan PF, Kendler KS (2003) Genetic and environmental contributions to obesity and binge eating. Int J Eat Disord 33:293–298PubMedGoogle Scholar
  131. 131.
    Schousboe K, Visscher PM, Erbas B, Kyvik KO, Hopper JL, Henriksen JE, et al (2004) Twin study of genetic and environmental influences on adult body size, shape, and composition. Int J Obes Relat Metab Disord 28:39–48PubMedGoogle Scholar
  132. 132.
    Boutin P, Froguel P (2001) Genetics of human obesity. Best Pract Res Clin Endocrinol Metab 15:391–404PubMedGoogle Scholar
  133. 133.
    Bell CG, Walley AJ, Froguel P (2005) The genetics of human obesity. Nat Rev Genet 6:221–234PubMedGoogle Scholar
  134. 134.
    Cota D, Woods SC (2005) The role of the endocannabinoid system in the regulation of energy homeostasis. Obesity and nutrition. Curr Opin Endocrinol Diabetes 12:338–351Google Scholar
  135. 135.
    Matias I, Di Marzo V (2007) Endocannabinoids and the control of energy balance. Trends Endocrinol Metab 18:27–37PubMedGoogle Scholar
  136. 136.
    Loos RJ, Katzmarzyk PT, Rao DC, Rice T, Leon AS, Skinner JS, et al, HERITAGE Family Study. (2003) Genome-wide linkage scan for the metabolic syndrome in the HERITAGE Family Study. J Clin Endocrinol Metab 88:5935–5943PubMedGoogle Scholar
  137. 137.
    Sipe JC, Waalen J, Gerber A, Beutler E (2005) Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes 29:755–759Google Scholar
  138. 138.
    Comings DE, Muhleman D, Gade R, Johnson P, Verde R, Saucier G, et al (1997) Cannabinoid receptor gene (CNR1): association with i.v. drug use. Mol Psychiatry 2:161–168PubMedGoogle Scholar
  139. 139.
    Ampuero I (2005) Análisis molecular de los genes del sistema endocannabinoide CNR1 y FAAH en dos condiciones psiquiátricas: alcoholismo y depresión comórbida a la enfermedad de Parkinson. Doctoral thesis, Universidad Complutense, MadridGoogle Scholar
  140. 140.
    Dong C, Li WD, Geller F, Lei L, Li D, Gorlova OY, et al (2005) Possible genomic imprinting of three human obesity-related genetic loci. Am J Hum Genet 76:427–437PubMedGoogle Scholar
  141. 141.
    Gazzerro P, Caruso MG, Notarnicola M, Misciagna G, Guerra V, Laezza C, et al (2007) Association between cannabinoid type-1 receptor polymorphism and body mass index in a southern Italian population. Int J Obes (Lond) 31(6):908–912Google Scholar
  142. 142.
    Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Janke J, Batkai S, et al (2005) Activation of the peripheral endocannabinoid system in human obesity. Diabetes 54:2838–2843PubMedGoogle Scholar
  143. 143.
    Bluher M, Engeli S, Kloting N, Berndt J, Fasshauer M, Batkai S, et al (2006) Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 55:3053–3060PubMedGoogle Scholar
  144. 144.
    Cote M, Matias I, Lemieux I, Petrosino S, Almeras N, Despres JP, et al (2007) Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 31:692–699Google Scholar
  145. 145.
    Boyd ST, Fremming BA (2005) Rimonabant-a selective CB1 antagonist. Ann Pharmacother 39:684–690PubMedGoogle Scholar
  146. 146.
    Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S, RIO-Europe Study Group. (2005) 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 365:1389–1397PubMedGoogle Scholar
  147. 147.
    Despres JP, Golay A, Sjostrom L, Rimonabant in Obesity-Lipids Study Group. (2005) Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353:2121–2134PubMedGoogle Scholar
  148. 148.
    Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, RIO-North America Study Group. (2006) Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 295:761–775PubMedGoogle Scholar
  149. 149.
    Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF, RIO-Diabetes Study Group. (2006) Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 368:1660–1672PubMedGoogle Scholar
  150. 150.
    Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, et al (2005) Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 142:532–546PubMedGoogle Scholar
  151. 151.
    Arias F, Sánchez S, Gorgojo JJ, Almóvar F, Fernández S, Llorente F (2006) Diferencias clínicas entre pacientes obesos mórbidos con y sin atracones. Endocrinol Nutr 53:440–447CrossRefGoogle Scholar
  152. 152.
    Pagotto U, Pasquali R (2005) Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors. Lancet 365:1363–1364PubMedGoogle Scholar
  153. 153.
    McLaughlin PJ, Winston KM, Limebeer CL, Parker LA, Makriyannis A, Salamone JD (2005) The cannabinoid CB1 antagonist AM 251 produces food avoidance and behaviors associated with nausea but does not impair feeding efficiency in rats. Psychopharmacology 180:286–293PubMedGoogle Scholar
  154. 154.
    De Vry J, Schreiber R, Eckel G, Jentzsch KR (2004) Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A. Eur J Pharmacol 483:55–63PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Psychiatric UnitFundación Hospital AlcorcónAlcorcón (Madrid)Spain

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