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Brain Type 1 Cannabinoid Receptor Availability in Patients with Anorexia and Bulimia Nervosa

      Background

      The endocannabinoid system is a possible target in the treatment of eating disorders. We used positron emission tomography to investigate the type 1 cannabinoid receptor (CB1R) in bulimic and anorectic patients.

      Methods

      We investigated 16 female bulimia nervosa patients (BN) (age = 23.8 ± 7.1 years) and 14 female anorexia nervosa patients (AN) (age = 20.5 ± 3.6 years) using the selective CB1R ligand [18F]MK-9470. The control group consisted of 19 age-matched women (age = 25.2 ± 8.5 years). Statistical parametric mapping (pfamily-wise error < .05) and volume-of-interest analyses of CB1R availability were performed.

      Results

      Global CB1R availability was significantly increased in cortical and subcortical brain areas in AN patients compared with healthy control subjects (+24.5%, p = .0003). Regionally, CB1R availability was increased in the insula in both AN and BN patients (p = .01 and p = .0004) and the inferior frontal and temporal cortex in AN patients only (p = .02).

      Conclusions

      Global CB1R upregulation in AN patients is a possible long-term compensatory mechanism to an underactive endocannabinoid system in anorectic conditions. There is a similarity in CB1R dysregulation both in AN and BN in the insular cortex, which is involved in the integration of interoceptive information, gustatory information, reward, and emotion processing.

      Key Words

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      References

        • Fairburn C.G.
        • Harrison P.J.
        Eating disorders.
        Lancet. 2003; 361: 407-416
        • van Kuyck K.
        • Gérard N.
        • Van Laere K.
        • Casteels C.
        • Pieters G.
        • Gabriëls L.
        • Nuttin B.
        Towards a neurocircuitry in anorexia nervosa: Evidence from functional neuroimaging studies.
        J Psychiatr Res. 2009; 43: 1133-1145
        • Di Marzo V.
        • Ligresti A.
        • Cristino L.
        The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation.
        Int J Obes (Lond). 2009; 33: S18--S24
        • Wilson R.I.
        • Nicoll R.A.
        Endocannabinoid signaling in the brain.
        Science. 2002; 296: 678-682
        • Addy C.
        • Wright H.
        • Van Laere K.
        • Gantz I.
        • Erondu N.
        • Musser B.J.
        • et al.
        The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake.
        Cell Metab. 2008; 7: 68-78
        • Beal J.E.
        • Olson R.
        • Lefkowitz L.
        • Laubenstein L.
        • Bellman P.
        • Yangco B.
        • et al.
        Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia.
        J Pain Symptom Manage. 1997; 14: 7-14
        • Siegfried Z.
        • Kanyas K.
        • Latzer Y.
        • Karni O.
        • Bloch M.
        • Lerer B.
        • Berry E.M.
        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
        • 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
        • Horcajadas F.A.
        Cannabinoids in eating disorders and obesity.
        Mol Neurobiol. 2007; 36: 113-128
        • Gross H.
        • Ebert M.H.
        • Faden V.B.
        • Goldberg S.C.
        • Kaye W.H.
        • Caine E.D.
        • et al.
        A double-blind trial of delta 9-tetrahydrocannabinol in primary anorexia nervosa.
        J Clin Psychopharmacol. 1983; 3: 165-171
        • Burns H.D.
        • Van Laere K.
        • Sanabria-Bohórquez S.
        • Hamill T.G.
        • Bormans G.
        • Eng W.S.
        • et al.
        [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor.
        Proc Natl Acad Sci U S A. 2007; 104: 9800-9805
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR (text Revision).
        4th ed. American Psychiatric Publishing, Washington, DC2000
        • Wagner A.
        • Greer P.
        • Bailer U.F.
        • Frank G.K.
        • Henry S.E.
        • Putnam K.
        • et al.
        Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.
        Biol Psychiatry. 2006; 59: 291-293
        • Vandereycken W.
        The Eating Disorder Evaluation Scale (EDES).
        Eat Disord. 1993; 1: 115-122
        • Garner D.M.
        Development and validation of a multidimensional Eating Disorder Inventory for anorexia nervosa and bulimia.
        Int J Eat Disord. 2007; 2: 15-34
        • Sanabria-Bohorquez S.M.
        • Hamill T.G.
        • Goffin K.
        • De Lepeleire I.
        • Bormans G.
        • Burns H.D.
        • Van Laere K.
        Kinetic analysis of the cannabinoid-1 receptor PET tracer [(18)F]MK-9470 in human brain.
        Eur J Nucl Med Mol Imaging. 2010; 37: 920-933
        • Thie J.A.
        • Hubner K.F.
        • Isidoro F.P.
        • Smith G.T.
        A weight index for the standardized uptake value in 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography.
        Mol Imaging Biol. 2007; 9: 91-98
        • Ashburner J.
        • Friston K.J.
        Voxel-based morphometry–the methods.
        Neuroimage. 2000; 11: 805-821
        • Solinas M.
        • Goldberg S.R.
        • Piomelli D.
        The endocannabinoid system in brain reward processes.
        Br J Pharmacol. 2008; 154: 369-383
        • Di Marzo V.
        Targeting the endocannabinoid system: To enhance or reduce?.
        Nat Rev Drug Discov. 2008; 7: 438-455
        • van der Stelt M.
        • Di Marzo V.
        The endocannabinoid system in the basal ganglia and in the mesolimbic reward system: Implications for neurological and psychiatric disorders.
        Eur J Pharmacol. 2003; 480: 133-150
        • Kirkham T.C.
        • Williams C.M.
        • 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
        • Hanus L.
        • Avraham Y.
        • Ben-Shushan D.
        • Zolotarev O.
        • Berry E.M.
        • Mechoulam R.
        Short-term fasting and prolonged semistarvation have opposite effects on 2-AG levels in mouse brain.
        Brain Res. 2003; 983: 144-151
        • Fride E.
        • Bregman T.
        • Kirkham T.C.
        Endocannabinoids and food intake: Newborn suckling and appetite regulation in adulthood.
        Exp Biol Med (Maywood). 2005; 230: 225-234
        • Pagotto U.
        • Vicennati V.
        • Pasquali R.
        The endocannabinoid system and the treatment of obesity.
        Ann Med. 2005; 37: 270-275
        • Hill M.N.
        • Patel S.
        • Carrier E.J.
        • Rademacher D.J.
        • Ormerod B.K.
        • Hillard C.J.
        • Gorzalka B.B.
        Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress.
        Neuropsychopharmacology. 2005; 30: 508-515
        • Gifford A.N.
        • Bruneus M.
        • Gatley S.J.
        • Lan R.
        • Makriyannis A.
        • Volkow N.D.
        Large receptor reserve for cannabinoid actions in the central nervous system.
        J Pharmacol Exp Ther. 1999; 288: 478-483
        • Hill M.N.
        • Hillard C.J.
        • Bambico F.R.
        • Patel S.
        • Gorzalka B.B.
        • Gobbi G.
        The therapeutic potential of the endocannabinoid system for the development of a novel class of antidepressants.
        Trends Pharmacol Sci. 2009; 30: 484-493
        • Monteleone P.
        • Serritella C.
        • Martiadis V.
        • Scognamiglio P.
        • Maj M.
        Plasma obestatin, ghrelin, and ghrelin/obestatin ratio are increased in underweight patients with anorexia nervosa but not in symptomatic patients with bulimia nervosa.
        J Clin Endocrinol Metab. 2008; 93: 4418-4421
        • Kola B.
        • Farkas I.
        • Christ-Crain M.
        • Wittmann G.
        • Lolli F.
        • Amin F.
        • et al.
        The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system.
        PLoS ONE. 2008; 3: e1797
        • Jelsing J.
        • Larsen P.J.
        • Vrang N.
        The effect of leptin receptor deficiency and fasting on cannabinoid receptor 1 mRNA expression in the rat hypothalamus, brainstem and nodose ganglion.
        Neurosci Lett. 2009; 463: 125-129
        • Di Marzo V.
        • Goparaju S.K.
        • Wang L.
        • Liu J.
        • Bátkai S.
        • Járai Z.
        • et al.
        Leptin-regulated endocannabinoids are involved in maintaining food intake.
        Nature. 2001; 410: 822-825
        • Thanos P.K.
        • Ramalhete R.C.
        • Michaelides M.
        • Piyis Y.K.
        • Wang G.J.
        • Volkow N.D.
        Leptin receptor deficiency is associated with upregulation of cannabinoid 1 receptors in limbic brain regions.
        Synapse. 2008; 62: 637-642
        • Maccarrone M.
        • Di Rienzo M.
        • Finazzi-Agrò A.
        • Rossi A.
        Leptin activates the anandamide hydrolase promoter in human T lymphocytes through STAT3.
        J Biol Chem. 2003; 278: 13318-13324
        • Golden N.H.
        • Carlson J.L.
        The pathophysiology of amenorrhea in the adolescent.
        Ann N Y Acad Sci. 2008; 1135: 163-178
        • Nagai M.
        • Kishi K.
        • Kato S.
        Insular cortex and neuropsychiatric disorders: A review of recent literature.
        Eur Psychiatry. 2007; 22: 387-394
        • Kaye W.
        Neurobiology of anorexia and bulimia nervosa.
        Physiol Behav. 2008; 94: 121-135
        • Ellison Z.
        • Foong J.
        • Howard R.
        • Bullmore E.
        • Williams S.
        • Treasure J.
        Functional anatomy of calorie fear in anorexia nervosa.
        Lancet. 1998; 352: 1192
        • Sachdev P.
        • Mondraty N.
        • Wen W.
        • Gulliford K.
        Brains of anorexia nervosa patients process self-images differently from non-self-images: An fMRI study.
        Neuropsychologia. 2008; 46: 2161-2168
        • Redgrave G.W.
        • Bakker A.
        • Bello N.T.
        • Caffo B.S.
        • Coughlin J.W.
        • Guarda A.S.
        • et al.
        Differential brain activation in anorexia nervosa to Fat and Thin words during a Stroop task.
        Neuroreport. 2008; 19: 1181-1185
        • Hungund B.L.
        • Vinod K.Y.
        • Kassir S.A.
        • Basavarajappa B.S.
        • Yalamanchili R.
        • Cooper T.B.
        • et al.
        Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victims.
        Mol Psychiatry. 2004; 9: 184-190
        • Schindler F.
        • Anghelescu I.
        • Regen F.
        • Jockers-Scherubl M.
        Improvement in refractory obsessive compulsive disorder with dronabinol.
        Am J Psychiatry. 2008; 165: 536-537
        • Lena S.M.
        • Fiocco A.J.
        • Leyenaar J.K.
        The role of cognitive deficits in the development of eating disorders.
        Neuropsychol Rev. 2004; 14: 99-113
        • Yoshizawa M.
        • Tashiro M.
        • Fukudo S.
        • Yanai K.
        • Utsumi A.
        • Kano M.
        • et al.
        Increased brain histamine H1 receptor binding in patients with anorexia nervosa.
        Biol Psychiatry. 2009; 65: 329-335
        • Galusca B.
        • Costes N.
        • Zito N.G.
        • Peyron R.
        • Bossu C.
        • Lang F.
        • et al.
        Organic background of restrictive-type anorexia nervosa suggested by increased serotonin (1A) receptor binding in right frontotemporal cortex of both lean and recovered patients: [(18)F]MPPF PET scan study.
        Biol Psychiatry. 2008; 64: 1009-1013
        • Chernyak Y.
        • Lowe M.R.
        Motivations for dieting: Drive for thinness is different from drive for objective thinness.
        J Abnorm Psychol. 2010; 119: 276-281
        • Stamatakis E.A.
        • Hetherington M.M.
        Neuroimaging in eating disorders.
        Nutr Neurosci. 2003; 6: 325-334
        • Castro-Fornieles J.
        • Bargalló N.
        • Lázaro L.
        • Andrés S.
        • Falcon C.
        • Plana M.T.
        • Junqué C.
        A cross-sectional and follow-up voxel-based morphometric MRI study in adolescent anorexia nervosa.
        J Psychiatr Res. 2009; 43: 331-340
        • Joos A.
        • Klöppel S.
        • Hartmann A.
        • Glauche V.
        • Tüscher O.
        • Perlov E.
        • et al.
        Voxel-based morphometry in eating disorders: Correlation of psychopathology with grey matter volume.
        Psychiatry Res. 2010; 182: 146-151
        • Suchan B.
        • Busch M.
        • Schulte D.
        • Grönemeyer D.
        • Herpertz S.
        • Vocks S.
        Reduction of gray matter density in the extrastriate body area in women with anorexia nervosa.
        Behav Brain Res. 2010; 206: 63-67