Several cardiometabolic factors present in obese and insulin-resistant individuals represent a continuum of increasing risk for the development of type 2 diabetes and cardiovascular disease. The importance of abdominal obesity as an independent risk factor is underscored by its association with adverse endocrine function. Recent evidence from animal and human studies has shown a role for the endocannabinoid system in maintaining energy balance and glucose and lipoprotein metabolism, with overactivity linked to aberrant glycemic and lipoprotein control, and a link to adiposity. Modulation of this system through endocannabinoid-receptor blockade has resulted in an improvement in a number of important risk factors in clinical trials, including visceral and subcutaneous abdominal adipose tissue, glucose tolerance, dyslipidemia and measures of inflammation. These findings may have significant implications for the management of patients at risk of developing cardiovascular and metabolic disease; however, the occurrence of psychiatric adverse events with rimonabant may preclude further development of centrally active endocannabinoid receptor antagonists for the treatment of cardiometabolic disorders. Future research is needed to explore the role of selective peripheral CB1 receptor antagonists in the treatment of patients at high cardiometabolic risk.

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–3421.
Grundy SM: Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006;47:1093–1100.
Kirkham TC: Endocannabinoids in the regulation of appetite and body weight. Behav Pharmacol 2005;16:297–313.
Bensaid M, Gary-Bobo M, Esclangon A, Maffrand JP, Le Fur G, Oury-Donat F, Soubrié P: 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;63:908–914.
Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G: Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005;115:1298–1305.
Engeli S, Böhnke J, Feldpausch M, Gorzelniak K, Janke J, Bátkai S, Pacher P, Harvey-White J, Luft FC, Sharma AM, Jordan J: Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005;54:2838–2843.
Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF: Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006;368:1660–1672.
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.
Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J: 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 2006;295:761–775.
Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S: 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;365:1389–1397.
McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Ballantyne CM, Heiss G: The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2005;28:385–390.
Girman CJ, Dekker JM, Rhodes T, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ: An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes: the Hoorn study. Am J Epidemiol 2005;162:438–447.
Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA: Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 2002;156:1070–1077.
Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709–2716.
Neyer JR, Greenlund KJ, Denny CH, Keenan NL, Labarthe DR, Croft JB: Racial/ethnic and socioeconomic disparities in multiple risk factors for heart disease and stroke – United States, 2003. MMWR Morb Mortal Wkly Rep 2005;54:113–117.
Kannel WB, Wilson PW, Nam BH, D’Agostino RB: Risk stratification of obesity as a coronary risk factor. Am J Cardiol 2002;90:697–701.
Eberly LE, Prineas R, Cohen JD, Vazquez G, Zhi X, Neaton JD, Kuller LH; Multiple Risk Factor Intervention Trial Research Group: Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial. Diabetes Care 2006;29:123–130.
Mosca L, Edelman D, Mochari H, Christian AH, Paultre F, Pollin I: Waist circumference predicts cardiometabolic and global Framingham risk among women screened during National Woman’s Heart Day. J Womens Health (Larchmt) 2006;15:24–34.
Rexrode KM, Buring JE, Manson JE: Abdominal and total adiposity and risk of coronary heart disease in men. Int J Obes Relat Metab Disord 2001;25:1047–1056.
Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, Willett WC, Manson JE: Abdominal adiposity and coronary heart disease in women. JAMA 1998;280:1843–1848.
Dagenais GR, Yi Q, Mann JF, Bosch J, Pogue J, Yusuf S: Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J 2005;149:54–60.
Lakka HM, Lakka TA, Tuomilehto J, Salonen JT: Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J 2002;23:706–713.
Seidell JC, Verschuren WM, Van Leer EM, Kromhout D: Overweight, underweight, and mortality. A prospective study of 48,287 men and women. Arch Intern Med 1996;156:958–963.
Boden G: Free fatty acids – the link between obesity and insulin resistance. Endocr Pract 2001;7:44–51.
Yamashita S, Nakamura T, Shimomura I, Nishida M, Yoshida S, Kotani K, Kameda-Takemuara K, Tokunaga K, Matsuzawa Y: Insulin resistance and body fat distribution. Diabetes Care 1996;19:287–291.
Lebovitz HE: The relationship of obesity to the metabolic syndrome. Int J Clin Pract Suppl 2003;134:18–27.
Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD: Splanchnic lipolysis in human obesity. J Clin Invest 2004;113:1582–1588.
Nieves DJ, Cnop M, Retzlaff B, Walden CE, Brunzell JD, Knopp RH, Kahn SE: The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat. Diabetes 2003;52:172–179.
Ribeiro Filho FF, Faria AN, Kohlmann O Jr, Ajzen S, Ribeiro AB, Zanella MT, Ferreira SR: Ultrasonography for the evaluation of visceral fat and cardiovascular risk. Hypertension 2001;38:713–717.
Onat A, Avci GS, Barlan MM, Uyarel H, Uzunlar B, Sansoy V: Measures of abdominal obesity assessed for visceral adiposity and relation to coronary risk. Int J Obes Relat Metab Disord 2004;28:1018–1025.
Faria AN, Ribeiro Filho FF, Gouveia Ferreira SR, Zanella MT: Impact of visceral fat on blood pressure and insulin sensitivity in hypertensive obese women. Obes Res 2002;10:1203–1206.
Pascot A, Després JP, Lemieux I, Alméras N, Bergeron J, Nadeau A, Prud’homme D, Tremblay A, Lemieux S: Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation. Diabetes Care 2001;24:902–908.
Piche ME, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J, Lemieux S: Contribution of abdominal visceral obesity and insulin resistance to the cardiovascular risk profile of postmenopausal women. Diabetes 2005;54:770–777.
Vettor R, Milan G, Rossato M, Federspil G: Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther 2005;22(suppl 2):3–10.
Matsuzawa Y: Therapy insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 2006;3:35–42.
Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C: The implication of obesity and central fat on markers of chronic inflammation: The ATTICA study. Atherosclerosis 2005;183:308–315.
Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–2556.
Matsuzawa Y: Therapy insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med 2006;3:35–42.
Hu FB, Meigs JB, Li TY, Rifai N, Manson JE: Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004;53:693–700.
Lihn AS, Pedersen SB, Richelsen B: Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev 2005;6:13–21.
Côté M, Mauriège P, Bergeron J, Alméras N, Tremblay A, Lemieux I, Després JP: Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men. J Clin Endocrinol Metab 2005;90:1434–1439.
Steffes MW, Gross MD, Schreiner PJ, Yu X, Hilner JE, Gingerich R, Jacobs DR Jr: Serum adiponectin in young adults – interactions with central adiposity, circulating levels of glucose, and insulin resistance: the CARDIA study. Ann Epidemiol 2004;14:492–498.
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–1935.
Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G: Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003;52:1779–1785.
Kopp HP, Krzyzanowska K, Mohlig M, Spranger J, Pfeiffer AF, Schernthaner G: Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women. Int J Obes (Lond) 2005;29:766–771.
Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF: Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003;361:226–228.
Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB: Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005;54:534–539.
Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, D’Andrea F, Molinari AM, Giugliano D: Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002;105:804–809.
Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ: Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA 2005;293:43–53.
Paré A, Dumont M, Lemieux I, Brochu M, Alméras N, Lemieux S, Prud’homme D, Després JP: Is the relationship between adipose tissue and waist girth altered by weight loss in obese men? Obes Res 2001;9:526–534.
Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I: Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise- induced weight loss in men. A randomized, controlled trial. Ann Intern Med 2000;133:92–103.
Park HS, Lee K: Greater beneficial effects of visceral fat reduction compared with subcutaneous fat reduction on parameters of the metabolic syndrome: a study of weight reduction programmes in subjects with visceral and subcutaneous obesity. Diabetes Med 2005;22:266–272.
Droyvold WB, Midthjell K, Nilsen TI, Holmen J: Change in body mass index and its impact on blood pressure: a prospective population study. Int J Obes (Lond) 2005;29:650–655.
Xydakis AM, Case CC, Jones PH, Hoogeveen RC, Liu MY, Smith EO, Nelson KW, Ballantyne CM: Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. J Clin Endocrinol Metab 2004;89:2697–2703.
Poobalan A, Aucott L, Smith WC, Avenell A, Jung R, Broom J, Grant AM: Effects of weight loss in overweight/obese individuals and long-term lipid outcomes – a systematic review. Obes Rev 2004;5:43–50.
Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D: Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003;289:1799–1804.
Wannamethee SG, Shaper AG, Lennon L: Reasons for intentional weight loss, unintentional weight loss, and mortality in older men. Arch Intern Med 2005;165:1035–1040.
Yan LL, Daviglus ML, Liu K, Stamler J, Wang R, Pirzada A, Garside DB, Dyer AR, Van Horn L, Liao Y, Fries JF, Greenland P: Midlife body mass index and hospitalization and mortality in older age. JAMA 2006;295:190–198.
Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, Temprosa M; Diabetes Prevention Program Research Group: Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Diabetes Care 2005;28:888–894.
Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH, Kahn SE: Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes 2004;53:2087–2094.
Goodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, Nevitt M, Holvoet P, Newman AB: Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med 2005;165:777–783.
Mori Y, Hoshino K, Yokota K, Yokose T, Tajima N: Increased visceral fat and impaired glucose tolerance predict the increased risk of metabolic syndrome in Japanese middle-aged men. Exp Clin Endocrinol Diabetes 2005;113:334–339.
De Petrocellis L, Cascio MG, Di Marzo V: The endocannabinoid system: a general view and latest additions. Br J Pharmacol 2004;141:765–774.
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.
Munro S, Thomas KL, Abu-Shaar M: Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61–65.
Cota D, Woods SC: The role of the endocannabinoid system in the regulation of energy homeostasis. Curr Opin Endocrinol Diab 2005;12:338–351.
Di Marzo V, Matias I: Endocannabinoid control of food intake and energy balance. Nat Neurosci 2005;8:585–589.
Mailleux P, Parmentier M, Vanderhaeghen JJ: Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. Neurosci Lett 1992;143:200–204.
Herkenham M, Lynn AB, Johnson MR, Melvin LS, De Costa BR, Rice KC: Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991;11:563–583.
Matsuda LA, Bonner TI, Lolait SJ: Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 1993;327:535–550.
Howlett AC: The cannabinoid receptors. Prostaglandins Other Lipid Mediat 2002;68–69:619–631.
Pertwee RG: Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997;74:129–180.
Coutts AA, Izzo AA: The gastrointestinal pharmacology of cannabinoids: an update. Curr Opin Pharmacol 2004;4:572–579.
Cota D, Marsicano G, Tschöp M, Grübler Y, Flachskamm C, Schubert M, Auer D, Yassouridis A, Thöne-Reineke C, Ortmann S, Tomassoni F, Cervino C, Nisoli E, Linthorst AC, Pasquali R, Lutz B, Stalla GK, Pagotto U: The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 2003;112:423–431.
Liu YL, Connoley IP, Wilson CA, Stock MJ: 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 (Lond) 2005;29:183–187.
Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R: The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006;27:73–100.
Juan-Picó P, Fuentes E, Bermúdez-Silva FJ, Javier Díaz-Molina F, Ripoll C, Rodríguez de Fonseca F, Nadal A: Cannabinoid receptors regulate Ca2+ signals and insulin secretion in pancreatic β-cell. Cell Calcium 2006;39:155–162.
Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C, Petrosino S, Hoareau L, Festy F, Pasquali R, Roche R, Maj M, Pagotto U, Monteleone P, Di Marzo V: Regulation, function, and dysregulation of endocannabinoids in models of adipose and β-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 2006;91:3171–3180.
Galiégue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P: Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995;232:54–61.
Roche R, Hoareau L, Bes-Houtmann S, Gonthier MP, Laborde C, Baron JF, Haffaf Y, Cesari M, Festy F: Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes. Histochem Cell Biol 2006;126:177–187.
Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA: Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005;310:329–332.
Galve-Roperh I, Sánchez C, Cortes ML, Del Pulgar TG, Izquierdo M, Guzmán M: Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med 2000;6:313–319.
Pertwee RG: Pharmacology of cannabinoid receptor ligands. Curr Med Chem 1999;6:635–664.
Freund TF, Katona I, Piomelli D: Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003;83:1017–1066.
Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, Hipkin RW: Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol 2000;57:1045–1050.
Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC: Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 2002;301:1020–1024.
Ross RA: Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 2003;140:790–801.
Piomelli D: The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003;4:873–884.
Sipe JC, Waalen J, Gerber A, Beutler E: Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 2005;29:755–759.
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.
Di Marzo V, Goparaju SK, Wang L, Liu J, Bátkai S, Jarál 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.
Kirkham TC, Williams CM, Fezza F, Di Marzo V: 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;136:550–557.
Landi M, Croci T, Rinaldi-Carmona M, Maffrand JP, Le Fur G, Manara L: Modulation of gastric emptying and gastrointestinal transit in rats through intestinal cannabinoid CB1 receptors. Eur J Pharmacol 2002;450:77–83.
Gómez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, Cippitelli A, Nava F, Piomelli D, Rodríguez de Fonseca F: A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 2002;22:9612–9617.
Burdyga G, Lal S, Varro A, Dimaline R, Thompson DG, Dockray GJ: Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 2004;24:2708–2715.
Chiang KP, Gerber AL, Sipe JC, Cravatt BF: 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 2004;13:2113–2119.
Monteleone P, Matias I, Martiadis V, De Petrocellis L, Maj M, Di Marzo V: Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology 2005;30:1216–1221.
Siegfried Z, Kanyas K, Latzer Y, Karni O, Bloch M, Lerer B, Berry EM: 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 2004;125B:126–130.
Ravinet-Trillou C, Delgorge C, Menet C, Arnone M, Soubrié P: CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004;28:640–648.
Jamshidi N, Taylor DA: Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 2001;134:1151–1154.
Williams CM, Kirkham TC: Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1999;143:315–317.
Arnone M, Maruani J, Chaperon F, Thiébot MH, Poncelet M, Soubrié 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.
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.
Poirier B, Bidouard JP, Cadrouvele C, Marniquet X, Staels B, O’Connor SE, Janiak P, Herbert JM: The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes Metab 2005;7:65–72.
European Medicines Agency: The European Medicines Agency recommends suspension of the marketing authorisation of Acomplia. Announcement 2008.
Jbilo O, Ravinet-Trillou C, Arnone M, Buisson I, Bribes E, Péleraux A, Pénarier G, Soubrié P, Le Fur G, Galiègue S, Casellas P: 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.
Ravinet-Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP, Soubrie P: Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003;284:R345–R353.
Després JP, Ross R, Boka G, Alméras N, Lemieux I; ADAGIO-Lipids Investigators: Effect of rimonabant on the high-triglyceride/low HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids Trial. Arterioscler Thromb Vasc Biol 2009;29:416–423.
Ruilope LM, Després JP, Scheen A, Pi-Sunyer X, Mancia G, Zanchetti A, Van Gaal L: Effect of rimonabant on blood pressure in overweight/obese patients with/without co-morbidities: analysis of pooled RIO study results. J Hypertens 2008;26:357–367.
Després JP, Van Gaal L, Golay A, Rissanen A: Rimonabant improves oral glucose tolerance in non-diabetic overweight/obese patients with/without comorbidities. ADA Annual Meeting Scientific Sessions. Washington, D.C., 2006.
Padwal R, Li SK, Lau DC: Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 2003;27:1437–1446.
Van Gaal LF, Scheen AJ, Rissanen AM, Rossner S, Hanotin C, Ziegler O: Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study. Eur Heart J 2008. Epub 15 April 2008.
Iranmanesh I, Rosenstock J, Hollander P: Rimonabant monotherapy for treatment of multiple cardiometabolic risk factors in treatment-naive patients with type 2 diabetes. Diabetes Med 2006;23(suppl 4):230.
Hollander PA, Amod A, Litwak LE: Rimonabant improves glycemic control in insulin-treated type 2 diabetes: the ARPEGGIO Trial (abstract No 330-OR). American Diabetes Association, San Francisco, Calif., June 2008.
Nissen SE, Nicholls SJ, Wolski K, Rodes-Cabau J, Cannon CP, Deanfield JE, Després JP, Kastelein JJ, Steinhubl SR, Kapadia S, Yasin M, Ruzyllo W, Gaudin C, Job B, Hu B, Bhatt DL, Lincoff AM, Tuzcu EM; STRADIVARIUS Investigators: Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 2008;299:1547–1560.
Sugamura K, Sugiyama S, Nozaki T, Matsuzawa Y, Izumiya Y, Miyata K, Takeya M, Ogawa H: Activated endocannabinoid system in corocary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation 2009;119:28–36.
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