• 1
    T. Rubino, E. Zamberletti, D. Parolaro. Adolescent exposure to cannabis as a risk factor for psychiatric disorders. J. Psychopharmacol. 2012, 26, 177.
  • 2
    M. Ben Amar. Cannabinoids in medicine: A review of their therapeutic potential. J. Ethnopharmacol. 2006, 105, 1.
  • 3
    W.A. Devane, F.A. Dysark, M.R. Johnson, L.S. Melvin, A.C. Howlett. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 1988, 34, 605.
  • 4
    E.M. Marco, M.S. García-Gutiérrez, F.J. Bermúdez-Silva, F.A. Moreira, F. Guimarães, J. Manzanares, M.P. Viveros. Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects. Front. Behav. Neurosci. 2011, 5, 63.
  • 5
    V. Di Marzo. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol. Res. 2009, 60, 77.
  • 6
    G. Turu, L. Hunyady. Signal transduction of the CB1 cannabinoid receptor. J. Mol. Endocrinol. 2010, 44, 75.
  • 7
    R.G. Pertwee. The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. AAPS J. 2005, 7, E625.
  • 8
    T. Bisogno, L. Hanus, L. De Petrocellis, S. Tchilibon, D.E. Ponde, I. Brandi, A.S. Moriello, J.B. Davis, R. Mechoulam, V. Di Marzo. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 2001, 134, 845.
  • 9
    R.G. Pertwee, A.C. Howlett, M.E. Abood, S.P. Alexander, V. Di Marzo, M.R. Elphick, P.J. Greasley, H.S. Hansen, G. Kunos, K. Mackie, R. Mechoulam, R.A. Ross. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol. Rev. 2010, 62, 588.
  • 10
    U. Pagotto, G. Marsicano, D. Cota, B. Lutz, R. Pasquali. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr. Rev. 2006, 27, 73.
  • 11
    C.M. Williams, P.J. Rogers, T.C. Kirkham. Hyperphagia in pre-fed rats following oral delta9-THC. Physiol. Behav. 1998, 65, 343.
  • 12
    C.M. Williams, T.C. Kirkham. Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine. Pharmacol. Biochem. Behav. 2002, 71, 333.
  • 13
    C.M. Williams, T.C. Kirkham. Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacol. (Berl.) 1999, 143, 315.
  • 14
    T.C. Kirkham, C.M. Williams, F. Fezza, V. Di Marzo. 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.
  • 15
    J.A. Farrimond, A.J. Hill, B.J. Whalley, C.M. Williams. Cannabis constituents modulate δ9-tetrahydrocannabinol-induced hyperphagia in rats. Psychopharmacol. (Berl). 2010a, 210, 97.
  • 16
    J.A. Farrimond, B.J. Whalley, C.M. Williams. A low-Δ9tetrahydrocannabinol cannabis extract induces hyperphagia in rats. Behav. Pharmacol. 2010b Oct 21.
  • 17
    G. Riedel, P. Fadda, S. McKillop-Smith, R.G. Pertwee, B. Platt, L. Robinson. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br. J. Pharmacol. 2009, 156, 1154.
  • 18
    J.A. Farrimond, B.J. Whalley, C.M. Williams. Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacol. (Berl.) 2012, 223, 117.
  • 19
    A.A. Scopinho, F.S. Guimarães, F.M. Corrêa, L.B. Resstel. Cannabidiol inhibits the hyperphagia induced by cannabinoid-1 or serotonin-1A receptor agonists. Pharmacol. Biochem. Behav. 2011, 98, 268.
  • 20
    T.C. Kirkham, C.M. Williams. Endogenous cannabinoids and appetite. Nutr. Res. Rev. 2001, 14, 65.
  • 21
    J.A. Farrimond, M.S. Mercier, B.J. Whalley, C.M. Williams. Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. Phytother. Res. 2011, 25, 170.
  • 22
    R. Gómez, M. Navarro, B. Ferrer, J.M. Trigo, A. Bilbao, I. Del Arco, A. Cippitelli, F. Nava, D. Piomelli, F. Rodríguez de Fonseca. A peripheral mechanism for CB1cannabinoid receptor-dependent modulation of feeding. J. Neurosci. 2002, 22, 9612.
  • 23
    G.J. Morton, D.E. Cummings, D.G. Baskin, G.S. Barsh, M.W. Schwartz. Central nervous system control of food intake and body weight. Nature 2006, 443, 289.
  • 24
    F.J. Bermudez-Silva, P. Cardinal, D. Cota. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J. Psychopharmacol. 2012, 26,114.
  • 25
    P. Cardinal, L. Bellocchio, S. Clark, A. Cannich, M. Klugmann, B. Lutz, G. Marsicano, D. Cota. Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology. 2012, 153(9), 413643.
  • 26
    C. Buettner, E.D. Muse, A. Cheng, L. Chen, T. Scherer, A. Pocai, K. Su, B. Cheng, X. Li, J. Harvey-White, G.J. Schwartz, G. Kunos, L. Rossetti, C. Buettner. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 2008, 14, 667.
  • 27
    G. Burdyga, S. Lal, A. Varro, R. Dimaline, D.G. Thompson, G.J. Dockray. Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J. Neurosci. 2004, 24, 2708.
  • 28
    A.N. Verty, A.M. Allen, B.J. Oldfield. The effects of rimonabant on brown adipose tissue in rat: implications for energy expenditure. Obesity (Silver Spring) 2009, 17, 254.
  • 29
    C. Quarta, L. Bellocchio, G. Mancini, R. Mazza, C. Cervino, L.J. Braulke, C. Fekete, R. Latorre, C. Nanni, M. Bucci, LE. Clemens, G. Heldmaier, M. Watanabe, T. Leste-Lassere, M. Maitre, L. Tedesco, F. Fanelli, S. Reuss, S. Klaus, R.K. Srivastava, K. Monory, A. Valerio, A. Grandis, R. De Giorgio, R. Pasquali, E. Nisoli, D. Cota, B. Lutz, G. Marsicano, U. Pagotto. CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance. Cell Metab. 2010, 11(4), 27385.
  • 30
    L. Bellocchio, E. Soria-Gómez, C. Quarta, M. Metna-Laurent, P. Cardinal, E. Binder, A. Cannich, A. Delamarre, M. Häring, M. Martín-Fontecha, D. Vega, T. Leste-Lasserre, D. Bartsch, K. Monory, B. Lutz, F. Chaouloff, U. Pagotto, M. Guzman, D. Cota, G. Marsicano. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade. Proc. Natl. Acad. Sci. U. S. A. 2013, 19, 4786.
  • 31
    V. Di Marzo, S.K. Goparaju, L. Wang, J. Liu, S. Bátkai, Z. Járai, F. Fezza, G.I. Miura, R.D. Palmiter, T. Sugiura, G. Kunos. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001, 410, 822.
  • 32
    J.G. Tasker. Rapid glucocorticoid actions in the hypothalamus as a mechanism of homeostatic integration. Obesity (Silver Spring) 2006, 14, S259S.
  • 33
    G. Burdyga, A. Varro, R. Dimaline, D.G. Thompson, G.J. Dockray. Expression of cannabinoid CB1 receptors by vagal afferent neurons: kinetics and role in influencing neurochemical phenotype. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G63.
  • 34
    E. Bojanowska, E. Radziszewska. Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat. J. Physiol. Pharmacol. 2011, 62, 395.
  • 35
    B. Gatta-Cherifi, I. Matias, M. Vallée, A. Tabarin, G. Marsicano, P.V. Piazza, D. Cota. Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity. Int. J. Obes. (Lond.) 2012, 36, 880.
  • 36
    K.C. Berridge, C.Y. Ho, J.M. Richard, A.G. DiFeliceantonio. The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res. 2010, 1350, 43.
  • 37
    S. Vlachou, G. Panagis. Regulation of brain reward by the endocannabinoid system: a critical review of behavioral studies in animals. Curr. Pharm. Des. 2013 Jun 14. [Epub ahead of print] PubMed PMID: 23829366.
  • 38
    T. Melis, S. Succu, F. Sanna, A. Boi, A. Argiolas, M.R. Melis. The cannabinoid antagonist SR 141716A (Rimonabant) reduces the increase of extra-cellular dopamine release in the rat nucleus accumbens induced by a novel high palatable food. Neurosci. Lett. 2007, 419, 231.
  • 39
    G. Labouèbe, S. Liu, C. Dias, H. Zou, J.C. Wong, S. Karunakaran, S.M. Clee, A.G. Phillips, B. Boutrel, S.L. Borgland. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat. Neurosci. 2013, 16, 300.
  • 40
    G.M. Leinninger, Y.H. Jo, R.L. Leshan, G.W. Louis, H. Yang, J.G. Barrera, H. Wilson, D.M. Opland, M.A. Faouzi, Y. Gong, J.C. Jones, C.J. Rhodes, S. Chua Jr, S. Diano, T.L. Horvath, R.J. Seeley, J.B. Becker, H. Münzberg, M.G. Myers Jr. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009, 10(2), 8998.
  • 41
    J.D. Hommel, R. Trinko, R.M. Sears, D. Georgescu, Z.W. Liu, X.B. Gao, J.J. Thurmon, M. Marinelli, R.J. DiLeone. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 2006, 51, 801.
  • 42
    E.R. Partosoedarso, T.P. Abrahams, R.T. Scullion, J.M. Moerschbaecher, P.J. Hornby. Cannabinoid1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets. J. Physiol. 2003, 550, 149.
  • 43
    D. Cota, G. Marsicano, M. Tschöp, Y. Grübler, C. Flachskamm, M. Schubert, D. Auer, A. Yassouridis, C. Thöne-Reineke, S. Ortmann, F. Tomassoni, C. Cervino, E. Nisoli, A.C. Linthorst, R. Pasquali, B. Lutz, G.K. Stalla, U. Pagotto. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Invest. 2003, 112, 423.
  • 44
    M. Bensaid, M. Gary-Bobo, A. Esclangon, J.P. Maffrand, G. Le Fur, F. Oury-Donat, P. Soubrié. 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.
  • 45
    I. Matias, M.P. Gonthier, P. Orlando, V. Martiadis, L. De Petrocellis, C. Cervino, S. Petrosino, L. Hoareau, F. Festy, R. Pasquali, R. Roche, M. Maj, U. Pagotto, P. Monteleone, V. Di Marzo. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J. Clin. Endocrinol. Metab. 2006, 91, 3171.
  • 46
    G.G. Muccioli, D. Naslain, F. Bäckhed, C.S. Reigstad, D.M. Lambert, N.M. Delzenne, P.D. Cani. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010, 6, 392.
  • 47
    N. Perwitz, J. Wenzel, I. Wagner, J. Büning, M. Drenckhan, K. Zarse, M. Ristow, W. Lilienthal, H. Lehnert, J. Klein. Cannabinoid type 1 receptor blockade induces transdifferentiation towards a brown fat phenotype in white adipocytes. Diabetes Obes. Metab. 2010, 12, 158.
  • 48
    A.W. Herling, S. Kilp, R. Elvert, G. Haschke, W. Kramer. Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats. Endocrinol. 2008, 149, 2557.
  • 49
    M. Bajzer, M. Olivieri, M.K. Haas, P.T. Pfluger, I.J. Magrisso, M.T. Foster, M.H. Tschöp, K.A. Krawczewski-Carhuatanta, D. Cota, S. Obici. Cannabinoid receptor 1 (CB1) antagonism enhances glucose utilisation and activates brown adipose tissue in diet-induced obese mice. Diabetologia 2011, 54, 3121.
  • 50
    D. Osei-Hyiaman, M. DePetrillo, P. Pacher, J. Liu, S. Radaeva, S. Bátkai, J. Harvey-White, K. Mackie, L. Offertáler, L. Wang, G. Kunos. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J. Clin. Invest. 2005, 115, 1298.
  • 51
    D. Osei-Hyiaman, J. Liu, I. Zhou, G. Godlewski, J. Harvey-White, W.I. Jeong, S. Bátkai, G. Marsicano, B. Lutz, C. Buettner, G. Kunos. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J. Clin. Invest. 2008, 118, 3160.
  • 52
    P. Cavuoto, A.J. McAinch, G. Hatzinikolas, A. Janovská, P. Game, G.A. Wittert. The expression of receptors for endocannabinoids in human and rodent skeletal muscle. Biochem. Biophys. Res. Commun. 2007, 364, 105.
  • 53
    K.A. Lindborg, M.K. Teachey, S. Jacob, E.J. Henriksen. Effects of in vitro antagonism of endocannabinoid-1 receptors on the glucose transport system in normal and insulin-resistant rat skeletal muscle. Diabetes Obes. Metab. 2010, 12, 722.
  • 54
    Y.L. Liu, I.P. Connoley, C.A. Wilson, M.J. Stock. 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.
  • 55
    C. Lipina, C. Stretton, S. Hastings, J.S. Hundal, K. Mackie, A.J. Irving, H.S. Hundal. Regulation of MAP kinase-directed mitogenic and protein kinase B-mediated signaling by cannabinoid receptor type 1 in skeletal muscle cells. Diabetes 2010, 59, 375.
  • 56
    F.J. Bermúdez-Silva, J. Suárez, E. Baixeras, N. Cobo, D. Bautista, A.L. Cuesta-Muñoz , E. Fuentes, P. Juan-Pico, M.J. Castro, G. Milman, R. Mechoulam, A. Nadal, F. Rodríguez de Fonseca. Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia 2008, 51, 476.
  • 57
    W. Kim, M.E. Doyle Z. Liu, Q. Lao, Y.K. Shin, O.D. Carlson, H.S. Kim, S. Thomas, J.K. Napora, E.K. Lee, R. Moaddel, Y. Wang, S. Maudsley, B. Martin, RN Kulkarni, JM Egan. Cannabinoids inhibit insulin receptor signaling in pancreatic β-cells. Diabetes 2011, 60, 1198.
  • 58
    F.J. Bermúdez-Silva, J. Suárez Pérez, A. Nadal, F. Rodríguez de Fonseca. The role of the pancreatic endocannabinoid system in glucose metabolism. Best Pract. Res. Clin. Endocrinol. Metab. 2009, 23, 87.
  • 59
    C. Li, P.M. Jones, S.J. Persaud. Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol. Ther. 2011, 129, 307.
  • 60
    P. Juan-Picó, E. Fuentes, F.J. Bermúdez-Silva, F. Javier Díaz-Molina, C. Ripoll, F. Rodríguez de Fonseca, A. Nadal. Cannabinoid receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell. Cell Calcium 2006, 39,155.
  • 61
    P. Juan-Pico, A.B. Ropero, E. Tuduri, I. Quesada, E. Fuentes, F.J. Bermudez-Silva, F. Rodriguez de Fonseca, A. Nadal. Regulation of glucose-induced [Ca2+]i signals by cannabinoid CB1 and CB2 receptors in pancreatic α- and δ-cells within intact islets of Langerhans. Obesity Metab. 2009, 5, 20.
  • 62
    L. Getty-Kaushik, A.M. Richard, J.T. Deeney, S. Krawczyk, O. Shirihai, B.E. Corkey. The CB1 antagonist rimonabant decreases insulin hypersecretion in rat pancreatic islets. Obesity (Silver Spring). 2009, 17, 1856.
  • 63
    V.F. Duvivier, L. Delafoy-Plasse, V. Delion, P. Lechevalier, J.C. Le Bail, E. Guillot, M.P. Pruniaux, A.M. Galzin. Beneficial effect of a chronic treatment with rimonabant on pancreatic function and beta-cell morphology in Zucker Fatty rats. Eur. J. Pharmacol. 2009, 616, 314.
  • 64
    WHO. Obesity and overweight.. Obesity and overweight. Fact Sheet No. 311. 2013. Available at: [1 August 2013].
  • 65
    C. Silvestri, V. Di Marzo. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab. 2013, 17(4), 47590.
  • 66
    C. Ravinet Trillou, M. Arnone, C. Delgorge, N. Gonalons, P. Keane, J.P. Maffrand, P. Soubrie. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 284, R345.
  • 67
    F.J. Bermudez-Silva, M.P. Viveros, J.M. McPartland, F. Rodriguez de Fonseca. The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacol. Biochem. Behav. 2010, 95, 375.
  • 68
    L.F. Van Gaal, A.M. Rissanen, A.J. Scheen, O. Ziegler, S. Rössner. RIO-Europe Study Group. 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.
  • 69
    F.X. Pi-Sunyer, L.J. Aronne, H.M. Heshmati, J. Devin, J. Rosenstock. RIO-North America Study Group. 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.
  • 70
    J.P. Després, A. Golay, L. Sjöström, Rimonabant in obesity-lipids study group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med. 2005, 353, 2121.
  • 71
    A.J. Scheen, N. Finer, P. Hollander, M.D. Jensen, L.F. Van Gaal. RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006, 368, 1660.
  • 72
    C. Addy, H. Wright, K. Van Laere, I. Gantz, N. Erondu, B.J. Musser, K. Lu, J. Yuan, S.M. Sanabria-Bohórquez, A. Stoch, C. Stevens, T.M. Fong, I. De Lepeleire, C. Cilissen J. Cote, K. Rosko, I.N. Gendrano III, A.M. Nguyen, B. Gumbiner, P. Rothenberg, J. de Hoon, G. Bormans, M. Depré, W.S. Eng, E. Ravussin, S. Klein, J. Blundell, G.A. Herman, H.D. Burns, R.J. Hargreaves, J. Wagner, K. Gottesdiener, J.M. Amatruda, S.B. Heymsfield. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab. 2008, 7, 68.
  • 73
    R. Nogueiras, C. Vyrat-Durebex, P.M. Suchanek, M. Klein, J. Tschöp, C. Caldwell, S.C. Woods, G. Wittmann, M. Watanabe, Z. Liposits, C. Fekete, O. Reizes, F. Rohner-Jeanrenaud, M.H. Tschöp. Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes 2008, 57, 2977.
  • 74
    J. Tam, V.K. Vemuri, J. Liu, S. Bátkai, B. Mukhopadhyay, G. Godlewski, D. Osei-Hyiaman, S. Ohnuma, S.V. Ambudkar, J. Pickel, A. Makriyannis, G. Kunos. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J. Clin. Invest. 2010, 120, 2953.
  • 75
    J. Tam, R. Cinar, J. Liu, G. Godlewski, D. Wesley, T. Jourdan, G. Szanda, B. Mukhopadhyay, L. Chedester, J.S. Liow, R.B. Innis, K. Cheng, K.C. Rice, J.R. Deschamps, R.J. Chorvat, J.F. McElroy, G. Kunos. Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab. 2012, 16, 167.
  • 76
    L.E. Klumpers, M. Fridberg, M.L. de Kam, P.B. Little, N.O. Jensen, H.D. Kleinloog, C.E. Elling, J.M. van Gerven. Peripheral selectivity of the novel cannabinoid receptor antagonist TM38837 in healthy subjects. Br. J. Clin. Pharmacol. 2013, doi:10.1111/bcp.12141.
  • 77
    G.T. Dodd, A.A. Worth, D.J. Hodkinson, R.K. Srivastava, B. Lutz, S.R. Williams, S.M. Luckman. Central functional response to the novel peptide cannabinoid, hemopressin. Neuropharmacol. 2013, 71, 27.
  • 78
    C. Silvestri, V. Di Marzo. Second generation CB1 receptor blockers and other inhibitors of peripheral endocannabinoid overactivity and the rationale of their use against metabolic disorders. Expert Opin. Investig. Drugs 2012, 21, 1309.
  • 79
    T. Bisogno, J.J. Burston, R. Rai, M. Allarà, B. Saha, A. Mahadevan, R.K. Razdan, J.L. Wiley, V. Di Marzo. Synthesis and pharmacological activity of a potent inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. ChemMedChem 2009, 4, 946.
  • 80
    T. Bisogno, A. Mahadevan, R. Coccurello, J.W. Chang, M. Allarà, Y. Chen, G. Giacovazzo, A. Lichtman, B. Cravatt, A. Moles, V. Di Marzo. A novel fluorophosphonate inhibitor of the biosynthesis of the endocannabinoid 2-arachidonoylglycerol with potential anti-obesity effects. Br. J. Pharmacol. 2013, 169, 784.
  • 81
    B. Batetta, M. Griinari, G. Carta, E. Murru, A. Ligresti, L. Cordeddu, E. Giordano, F. Sanna, T. Bisogno, S. Uda, M. Collu, I. Bruheim, V. Di Marzo, S. Banni. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats. J. Nutr. 2009, 139, 1495.
  • 82
    S. Banni, G. Carta, E. Murru, L. Cordeddu, E. Giordano, A.R. Sirigu, K. Berge, H. Vik, K.C. Maki, V. Di Marzo, M. Griinari. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects. Nutr. Metab. (Lond.) 2011, 30, 7.
  • 83
    B. Ignatowska-Jankowska, M.M. Jankowski, A.H. Swiergiel. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neurosci. Lett. 2011, 18, 82.
  • 84
    S.Y. Romero-Zerbo, M.S. Garcia-Gutierrez, J. Suárez, P. Rivera, I. Ruz-Maldonado, M. Vida, F. Rodriguez de Fonseca, J. Manzanares, F.J. Bermúdez-Silva. Overexpression of cannabinoid CB2 receptor in the brain induces hyperglycaemia and a lean phenotype in adult mice. J. Neuroendocrinol. 2012, 24, 1106.