Skip to main content

Advertisement

SpringerLink
Log in

Pharmacological Interventions for Obesity: Current and Future Targets

  • Food Addiction (A Meule, Section Editor)
  • Published:
Current Addiction Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Obesity in the USA has been on a constant rise since the Center for Disease Control and Prevention (CDC) began tracking it over 50 years ago. Despite focused attention on this epidemic, pharmacological treatments aimed at obesity are lacking. Here, we briefly give perspective on the central and peripheral mechanisms underlying feeding behaviors and describe the existing pharmacological treatments for obesity. With this lens, I suggest future targets for the treatment of obesity.

Recent Findings

Given the development of genetic and molecular tools, understanding of how energy expenditure is modulated is becoming more nuanced. There is growing evidence for a link between obesity and addiction, which should be utilized in the development of new pharmacological treatments.

Summary

More focus is needed on identifying targets for anti-obesity pharmacology. In doing so, research should include intensive investigation of the brain’s reward circuitry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Fryar CD, Carroll MD, Ogden CL (2016) Prevalence of overweight, obesity, and extreme obesity among adults aged 20 and over: United States, 1960–1962 through 2013–2014.

  2. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA. 2016;315:2284–91.

    Article  PubMed  CAS  Google Scholar 

  3. Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol. 2010;316:104–8.

    Article  PubMed  CAS  Google Scholar 

  4. Kim DD, Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Heal. 2016;19:602–13.

    Article  Google Scholar 

  5. Tremmel M, Gerdtham U-G, Nilsson P, Saha S. Economic burden of obesity: a systematic literature review. Int J Environ Res Public Health. 2017;14:435.

    Article  PubMed Central  Google Scholar 

  6. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342–62.

    Article  PubMed  CAS  Google Scholar 

  7. Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. Anat Rec. 1940;78:149–72.

    Article  Google Scholar 

  8. Heijboer AC, Pijl H, Van den Hoek AM, Havekes LM, Romijn JA, Corssmit EPM. Gut-brain axis: regulation of glucose metabolism. J Neuroendocrinol. 2006;18:883–94.

    Article  PubMed  CAS  Google Scholar 

  9. Schwartz MW, Porte D (2005) Diabetes, Obesity, and the Brain. Science (80- ) 307:375–379.

  10. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science (80- ) 278:135–138.

  11. Clark JT, Kalra PS, Crowley WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology. 1984;115:427–9.

    Article  PubMed  CAS  Google Scholar 

  12. Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14:351–5.

    Article  PubMed  CAS  Google Scholar 

  13. Betley JN, Cao ZFH, Ritola KD, Sternson SM. Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell. 2013;155:1337–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Nakajima KI, Cui Z, Li C, Meister J, Cui Y, Fu O, et al. Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat Commun. 2016;7:10268.

  15. Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, et al. Rapid, reversible activation of AgRP neurons drdives feeding behavior in mice. J Clin Invest. 2011;121:1424–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, et al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci. 2005;8:1289–91.

    Article  PubMed  CAS  Google Scholar 

  17. Luquet S, Perez FA, Hnasko TS, Palmiter RD (2005) NPY/AgRP neurons are essentials for feeding in adult mice but can be ablated in neonates. Science (80- ) 310:683–685.

  18. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385:165–8.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang X, Van Den Pol AN. Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis. Nat Neurosci. 2016;19:1341–7.

    Article  PubMed  CAS  Google Scholar 

  20. Stuber GD, Wise RA. Lateral hypothalamic circuits for feeding and reward. Nat Neurosci. 2016;19:198–205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Wang D, He X, Zhao Z, Feng Q, Lin R, Sun Y, et al. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Front Neuroanat. 2015;9:40.

  22. Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol. 1954;47:419–27.

    Article  PubMed  CAS  Google Scholar 

  23. Hoebel BG, Teitelbaum P (1962) Hypothalamic control of feeding and self-stimulation. Science (80- ) 135:375–377.

  24. Jennings JH, Rizzi G, Stamatakis AM, Ung RL, Stuber GD (2013) The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding. Science (80- ) 341:1517–1521.

  25. Stamatakis AM, Van Swieten M, Basiri ML, Blair GA, Kantak P, Stuber GD. Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward. J Neurosci. 2016;36:302–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. • Jennings JH, Ung RL, Resendez SL, et al (2015) Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160:516–527. While it has been long indicated that the lateral hypothalamus is involved in feeding behaviors, this paper elegantly begins to tease apart the specific contributions of different cell types within the brain region.

  27. Navarro M, Olney JJ, Burnham NW, Mazzone CM, Lowery-Gionta EG, Pleil KE, et al. Lateral hypothalamus GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. Neuropsychopharmacology. 2016;41:1505–12.

    Article  PubMed  CAS  Google Scholar 

  28. Qualls-Creekmore E, Yu S, Francois M, Hoang J, Huesing C, Bruce-Keller A, et al. Galanin-expressing GABA neurons in the lateral hypothalamus modulate food reward and noncompulsive locomotion. J Neurosci. 2017;37:6053–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. • Nieh EH, Matthews GA, Allsop SA, Presbrey KN, Leppla CA, Wichmann R, et al. Decoding neural circuits that control compulsive sucrose seeking. Cell. 2015;160:528–41. New techniques have allowed for detailed probing of circuitry regulating reward and feeding. This set of studies examines the VTA-LHA connection, identifying circuitry that may control compulsive consumption of a palatable food, while not effecting homeostatic feeding.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Inutsuka A, Inui A, Tabuchi S, Tsunematsu T, Lazarus M, Yamanaka A. Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons. Neuropharmacology. 2014;85:451–60.

    Article  PubMed  CAS  Google Scholar 

  31. Haynes AC, Chapman H, Taylor C, Moore GBT, Cawthorne MA, Tadayyon M, et al. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul Pept. 2002;104:153–9.

    Article  PubMed  CAS  Google Scholar 

  32. Broberger C, De Lecea L, Sutcliffe JG, Hokfelt T. Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J Comp Neurol. 1998;402:460–74.

    Article  PubMed  CAS  Google Scholar 

  33. Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, et al. Leptin acts via leptin receptor- expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 2009;10:89–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Qu D, Ludwig DS, Gammeltoft S, Piper M, Pelleymounter MA, Cullen MJ, et al. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature. 1996;380:243–7.

    Article  PubMed  CAS  Google Scholar 

  35. Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest. 2001;107:379–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Zhou QY, Palmiter RD. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell. 1995;83:1197–209.

    Article  PubMed  CAS  Google Scholar 

  37. Darvas M, Wunsch AM, Gibbs JT, Palmiter RD. Dopamine dependency for acquisition and performance of Pavlovian conditioned response. Proc Natl Acad Sci. 2014;111:2764–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Palmiter RD. Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci. 2007;30:375–81.

    Article  PubMed  CAS  Google Scholar 

  39. Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 2011;14:313–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Rada P, Avena NM, Hoebel BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience. 2005;134:737–44.

    Article  PubMed  CAS  Google Scholar 

  41. Liang N-C, Hajnal A, Norgren R. Sham feeding corn oil increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1236–9.

    Article  PubMed  CAS  Google Scholar 

  42. Friend DM, Devarakonda K, O’Neal TJ, Skirzewski M, Papazoglou I, Kaplan AR, et al. Basal ganglia dysfunction contributes to physical inactivity in obesity. Cell Metab. 2017;25:312–21.

    Article  PubMed  CAS  Google Scholar 

  43. Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13:635–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Cope MB, Nagy TR, Fernández JR, Geary N, Casey DE, Allison DB. Antipsychotic drug-induced weight gain: development of an animal model. Int J Obes. 2005;29:607–14.

    Article  CAS  Google Scholar 

  45. Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol. 2010;6:255–69.

    Article  PubMed  CAS  Google Scholar 

  46. Voigt JP, Fink H. Serotonin controlling feeding and satiety. Behav Brain Res. 2015;277:14–31.

    Article  PubMed  CAS  Google Scholar 

  47. Sohn JW, Elmquist JK, Williams KW. Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci. 2013;36:504–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology. 2002;123:1120–8.

    Article  PubMed  CAS  Google Scholar 

  49. Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, Lowell BB, et al. Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J Clin Invest. 1995;96:1658–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.

    Article  PubMed  CAS  Google Scholar 

  51. Lönnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med. 1995;1:950–3.

    Article  PubMed  Google Scholar 

  52. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411:480–4.

    Article  PubMed  CAS  Google Scholar 

  53. Figlewicz DP, Naleid AMD, Sipols AJ. Modulation of food reward by adiposity signals. Physiol Behav. 2007;91:473–8.

    Article  PubMed  CAS  Google Scholar 

  54. Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science. 2000;287:125–8.

    Article  PubMed  CAS  Google Scholar 

  55. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron. 2006;51:801–10.

    Article  PubMed  CAS  Google Scholar 

  56. Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron. 2006;51:811–22.

    Article  PubMed  CAS  Google Scholar 

  57. Al-Massadi O, Heppner KM, Nogueiras R, Pérez-Tilve D, Tschöp MH. Ghrelin. In: Handb. Biol. Act. Pept: Elsevier; 2013. p. 1104–10.

  58. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85:495–522.

    Article  PubMed  CAS  Google Scholar 

  59. Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol. 2011;340:80–7.

    Article  PubMed  CAS  Google Scholar 

  60. Koch M, Varela L, Kim JG, Kim JD, Hernández-Nuño F, Simonds SE, et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature. 2015;519:45–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Cains S, Blomeley C, Kollo M, Rácz R, Burdakov D. Agrp neuron activity is required for alcohol-induced overeating. Nat Commun. 2017;8:14014.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Leibowitz SF, Avena NM, Chang G-Q, Karatayev O, Chau DT, Hoebel BG. Ethanol intake increases galanin mRNA in the hypothalamus and withdrawal decreases it. Physiol Behav. 2003;79:103–11.

    Article  PubMed  CAS  Google Scholar 

  63. Velazquez A, Apovian CM. Updates on obesity pharmacotherapy. Ann N Y Acad Sci. 2018;1411:106–119.

  64. Baumann MH, Ayestas MA, Dersch CM, Brockington A, Rice KC, Rothman RB. Effects of phentermine and fenfluramine on extracellular dopamine and serotonin in rat nucleus accumbens: therapeutic implications. Synapse. 2000;36:102–13.

    Article  PubMed  CAS  Google Scholar 

  65. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity. JAMA. 2014;311:74–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Bray GA, Frühbeck G, Ryan DH, Wilding JPH. Management of obesity. Lancet. 2016;387:1947–56.

    Article  PubMed  Google Scholar 

  67. Srivastava G, Apovian CM. Current pharmacotherapy for obesity. Nat Rev Endocrinol. 2018;14:12–24.

    Article  PubMed  CAS  Google Scholar 

  68. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595–605.

    Article  PubMed  CAS  Google Scholar 

  69. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155–61.

    Article  PubMed  CAS  Google Scholar 

  70. Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067–77.

    Article  PubMed  CAS  Google Scholar 

  71. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11–22.

    Article  PubMed  CAS  Google Scholar 

  72. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341–52.

    Article  PubMed  CAS  Google Scholar 

  73. Thomas CE, Mauer EA, Shukla AP, Rathi S, Aronne LJ. Low adoption of weight loss medications: a comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity. 2016;24:1955–61.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Apovian CM, Istfan NW. Obesity: guidelines, best practices, new research. Endocrinol Metab Clin N Am. 2016;45:xvii–xviii.

    Article  Google Scholar 

  75. Brashier DBS, Sharma AK, Dahiya N, Singh SK, Khadka A. Lorcaserin: a novel antiobesity drug. J Pharmacol Pharmacother. 2014;5:175–8.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Allison DB, Gadde KM, Garvey WT, Peterson CA, Schwiers ML, Najarian T, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20:330–42.

    Article  PubMed  CAS  Google Scholar 

  77. Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity. 2013;21:2163–71.

    Article  PubMed  CAS  Google Scholar 

  78. Martinussen C, Bojsen-Moller KN, Svane MS, Dejgaard TF, Madsbad S. Emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2016;0:1–13.

    Google Scholar 

  79. Burcelin R, Gourdy P. Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity. Obes Rev. 2017;18:86–98.

    Article  PubMed  CAS  Google Scholar 

  80. Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124:4473–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. McElroy SL, Hudson JI, Mitchell JE, Wilfley D, Ferreira-Cornwell MC, Gao J, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72:235–46.

    Article  PubMed  Google Scholar 

  82. Vamado PJ, Williamson DA, Bentz BG, Ryan DH, Rhodes SK, O’Neil PM, et al. Prevalence of binge eating disorder in obese adults seeking weight loss treatment. Eat Weight Disord. 1997;2:117–24.

    Article  PubMed  CAS  Google Scholar 

  83. Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Kakkar AK, Dahiya N. Drug treatment of obesity: current status and future prospects. Eur J Intern Med. 2015;26:89–94.

    Article  PubMed  CAS  Google Scholar 

  85. Hendricks EJ. Off-label drugs for weight management. Diabetes, Metab Syndr Obes Targets Ther. 2017;10:223–34.

    Article  Google Scholar 

  86. Ahima RS, Antwi DA. Brain regulation of appetite and satiety. Endocrinol Metab Clin N Am. 2008;37:811–23.

    Article  CAS  Google Scholar 

  87. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854–9.

    Article  PubMed  CAS  Google Scholar 

  88. Volkow ND, Wang GJ, Tomasi D, Baler RD. Obesity and addiction: neurobiological overlaps. Obes Rev. 2013;14:2–18.

    Article  PubMed  CAS  Google Scholar 

  89. Bocarsly ME. Neuropathology of drug addictions and substance misuse. In: Preedy VR, editor. Neuropathol. Drug Addict. Subst. Misuse; 2016. p. 1–1143.

    Google Scholar 

  90. Craddock D. Anorectic drugs: use in general practice. Drugs. 1976;11:378–93.

    Article  PubMed  CAS  Google Scholar 

  91. Blanck HM, Serdula MK, Gillespie C, Galuska DA, Sharpe PA, Conway JM, et al. Use of nonprescription dietary supplements for weight loss is common among Americans. J Am Diet Assoc. 2007;107:441–7.

    Article  PubMed  Google Scholar 

  92. Manore MM. Dietary supplements for improving body composition and reducing body weight: where is the evidence? Int J Sport Nutr Exerc Metab. 2012;22:139–54.

    Article  PubMed  CAS  Google Scholar 

  93. Cameron JD, Chaput J-P, Sjödin AM, Goldfield GS. Brain on fire: incentive salience, hedonic hot spots, dopamine, obesity, and other hunger games. Annu Rev Nutr. 2017;37:183–205.

    Article  PubMed  CAS  Google Scholar 

  94. S.A. D (2009) Tesofensine—a novel potent weight loss medicine. Expert Opin Investig Drugs 18:1043–1046.

  95. Volkow ND, Baler RD. Addiction science: uncovering neurobiological complexity. Neuropharmacology. 2014;76:235–49.

    Article  PubMed  CAS  Google Scholar 

  96. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35:217–38.

    Article  PubMed  Google Scholar 

  97. Dobbs LK, Lemos JC, Alvarez VA. Restructuring of basal ganglia circuitry and associated behaviors triggered by low striatal D2 receptor expression: implications for substance use disorders. Genes, Brain Behav. 2017;16:56–70.

    Article  CAS  Google Scholar 

  98. Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Buchheimer N, et al. PET imaging of dopamine D2 receptors during chronic cocaine self- administration in monkeys. Nat Neurosci. 2006;9:1050–6.

    Article  PubMed  CAS  Google Scholar 

  99. Dalley JW, Fryer TD, Brichard L, et al (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science (80- ) 315:1267–1270.

  100. Volkow ND, Wang G-J, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc B Biol Sci. 2008;363:3191–200.

    Article  Google Scholar 

  101. • Schulte EM, Gearhardt AN. Development of the modified Yale food addiction scale version 2.0. Eur Eat Disord Rev. 2017;25:302–8. The Yale Food Addiction Scale (YFAS) provides a means of operationalizing indications of addictive-like eating. This recent article validates an updated version of the scale based on the DSM-5 diagnostic criteria.

    Article  PubMed  Google Scholar 

  102. Long CG, Blundell JE, Finlayson G. A systematic review of the application and correlates of YFAS-diagnosed “food addiction” in humans: are eating-related “addictions” a cause for concern or empty concepts? Obes Facts. 2015;8:386–401.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Gearhardt AN, White MA, Masheb RM, Morgan PT, Crosby RD, Grilo CM. An examination of the food addiction construct in obese patients with binge eating disorder. Int J Eat Disord. 2012;45:657–63.

    Article  PubMed  Google Scholar 

  104. Davis C, Levitan RD, Kaplan AS, Kennedy JL, Carter JC. Food cravings, appetite, and snack-food consumption in response to a psychomotor stimulant drug: the moderating effect of “food-addiction.”. Front Psychol. 2014;5:403.

  105. Melis M, Gessa GL, Diana M. Different mechanisms for dopaminergic excitation induced by opiates and cannabinoids in the rat midbrain. Prog Neuro- Psychopharmacology Biol Psychiatry. 2000;24:993–1006.

    Article  CAS  Google Scholar 

  106. Navarro M, Carrera MR, Fratta W, Valverde O, Cossu G, Fattore L, et al. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci. 2001;21:5344–50.

    Article  PubMed  CAS  Google Scholar 

  107. Kunos G. Understanding metabolic homeostasis and imbalance: what is the role of the endocannabinoid system? Am J Med. 2007;120:S18–24.

    Article  PubMed  CAS  Google Scholar 

  108. Fong TM, Heymsfield SB. Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions. Int J Obes. 2009;33:947–55.

    Article  CAS  Google Scholar 

  109. Yanovski SZ, Yanovski JA. Naltrexone-extended release plus bupropion-extended release for treatment of obesity. JAMA. 2015;313:1213–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute on Alcohol Abuse and Alcoholism, NIH Intramural Research Program, 5625 Fishers Lane, TS-32, Bethesda, MD, 20892-9411, USA

    Miriam E. Bocarsly

  2. National Institute of General Medical Sciences, NIH Intramural Research Program, Bethesda, MD, USA

    Miriam E. Bocarsly

Authors
  1. Miriam E. Bocarsly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miriam E. Bocarsly.

Ethics declarations

Conflict of Interest

The author declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Additional information

This article is part of the Topical Collection on Food Addiction

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bocarsly, M.E. Pharmacological Interventions for Obesity: Current and Future Targets. Curr Addict Rep 5, 202–211 (2018). https://doi.org/10.1007/s40429-018-0204-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40429-018-0204-0

Keywords

Search

Navigation