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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
J Genet Syndr Gene Ther. Author manuscript; available in PMC 2013 July 1.
Published in final edited form as:
J Genet Syndr Gene Ther. 2013 April 1; 4(3): 131.
doi:  10.4172/2157-7412.1000131
PMCID: PMC3697760

Pharmacotherapies for Overeating and Obesity


Obesity has become pandemic, and the annual cost in related illnesses and loss of productivity is already over $100 billion and rising. Research has shown that obesity can and does cause changes in behavior and in the brain itself that are very similar to changes caused by drugs of abuse. While food addiction is not the causal agent of all obesity, it is clear that many people no longer eat to survive, but instead survive to eat. This review considers the importance of the brain’s reward system in food intake. The review also examines research developments and current treatments for obesity, including diet and exercise, psychotherapy, surgical interventions, and pharmacotherapies. Finally we discuss alterations in American society that are necessary for change to occur, and the diffculties therein.

Keywords: Obesity, Pharmacotherapies, Dopamine, Brain reward circuitry, Social change, Reward Deficiency Syndrome (RDS)


Food addiction may play a role in the obesity epidemic. Obesity has reached pandemic proportions and is rapidly surpassing smoking as the number one killer in the industrialized world, as well as costing an estimated $117 billion annually in related illnesses and loss of productivity [13]. As the number of persons diagnosed with obesity continues to rise every year, many people are seeking answers for why so many people struggle with these issues. While food addiction certainly does not explain all cases of obesity, the increased number of persons with interest in eating above that which is required for the basic energetic needs of survival, suggests that food intake is no longer simply for survival purposes [4]. It has been demonstrated that rats overeating sugar solution developed many behavioral and brain changes resembling the effects of drugs of abuse [57]. Also similar to drug addictions, the reward circuitry of the brain, especially the dopaminergic system, was found to be involved in animals overfed highly palatable foods [813].

Not all foods are currently implicated in the development of food addictions [14]. Foods that are thought to be addictive tend to be highly palatable and are rich in fats, sugars, salt, and are calorie dense [4]. Further, these foods often are comprised of synthetic combinations of ingredients that may make them more potentially addictive than traditional foods [15]. Beyond this, research has recently demonstrated that each of these nutrient elements affects specific neurotransmitter systems in the brain [6,1618], providing the potential for targeted pharmacologic treatments [19,20]. With the soaring numbers of individuals affected with obesity, many of whom are children, it is important to seriously evaluate some of these new treatment modalities.

Reward system in food intake

Motivational abnormalities such as excessive overeating have been linked with changes in the mesocorticolimbic system of the brain, a complex and interrelated network with many functions, including food addiction [21]. Principal components of the mesocorticolimbic reward circuit consist of the amygdala, hippocampus, nucleus accumbens (ventral striatum), and ventral diencephalon (including the basal forebrain, ventral tegmentum, and hypothalamus), as well as cortical areas that provide modulating and oversight functions, such as the dorsolateral prefrontal, orbitofrontal, temporal pole, subcallosal, and cingulate cortices, parahippocampal gyri, and the insula. Dysfunctional eating may reflect an underlying addictive state.

Eating is essential for the survival of all living organisms [22], and even relatively brief durations of starvation, e.g., days, can lead to detrimental physical and psychological changes [23,24]. Therefore, eating behaviors are programed in the brain by powerful neural systems to ensure food-intake and to regulate caloric balance. These feeding behaviors are, however, controlled by more than homeostatic mechanisms. As it has been pointed out, “If feeding were controlled solely by homeostatic mechanisms, most of us would be at our ideal body weight, and people would consider feeding like breathing or elimination, a necessary but unexciting part of existence” [25]. The fact that this is not the case suggests that there is a role for the reward systems in the brain to promote motivational, hedonically-driven feeding. Thus, excessive food intake may be explained more by dysfunction in the reward circuitry than strictly dysfunction in the homeostatic mechanisms controlling feeding habits. Studies in human and nonhuman animals alike have supported the hypothesis that brain’s reward circuitry may be dysregulated in cases of obesity, disordered eating, and more recently, food addiction [512,26].

Genetics may play a role in the underlying addictive feeding. As not everyone who is exposed to drugs becomes an addict, similarly, not every person exposed to high-risk foods goes on to compulsively over eat. The difference in susceptibility can be attributed, at least in part, to underlying genetic predispositions, specifically, down-regulation of dopamine D2 receptors [2730]. One particular dopamine receptor genetic polymorphism, the TaqIA A1 allele, has been implicated specifically in obesity and substance use disorders through increases in reward sensitivity in the striatum by elevated dopamine activity levels [3133]. It follows then, that new forms of treatment, largely pharmaceutical, would potentially target these genetic predispositions as a means of intervention. This paper outlines some of the existing modalities of treatment with emphasis on pharmacologic interventions.

Diet and exercise

Although obesity often is described as an imbalance between caloric intake and energy expenditure, diet and exercise alone are not enough to combat most cases of obesity. Nonetheless, there is a simplified view suggesting that obesity is the fault of the obese individual due to excessive consumption, inadequate activity, or a combination of the two, resulting in much of the stigma that is associated with this condition [34]. While decreased caloric consumption and increased physical activity can be effective in normalizing weight, these lifestyle modifications have proven very difficult to sustain [35]. Studies have found that when dieting, the rate of initial weight loss can be rapid and then slowly declines over time such that the point of maximum weight loss is typically around six months after the initiation of treatment. After this point weight regain typically begins and gradually increases until stabilizing at a point usually somewhat below baseline level [36]. This pattern seems to remain independent of the initial weight loss, and aggressive maintenance strategies have been able to slow, but not prevent the rate of regain over time [37]. Further, adherence to these maintenance strategies typically slows over time, thereby failing to prevent relapse [38], and the expenditure of time and money to implement these maintenance strategies generally renders them impractical to any large-scale, community-based intervention [39]. The failure of many of these lifestyle modifications to reduce obesity over the long term suggests that obesity may not be entirely a metabolic disorder, but likely has a neuropsychogenic component [35]. While food addiction certainly does not explain all cases of obesity, the prevalence of people who eat for reasons other than obtaining energy suggests that other factors may play a role in motivating and/or reinforcing feeding behaviors. With the rapidly increasing number of cases of obesity, it may be time to consider new ways of understanding and approaching this problem. Moreover, it is well-known that carrying the DRD2 A1 allele results in reduced energy expenditure but a higher requirement for food reinforcement [40].


The study of food addiction is relatively new, and specialized treatment approaches have not yet been developed. However, because of overlaps between binge eating, obesity, and food addiction, it is possible that strategies that are effective for treating binge eating and obesity also may prove helpful in the treatment of food addiction. Certain types of psychotherapy, including cognitive behavioral therapy (CBT), cognitive behavioral therapy with guided self-help (CBT-gsh), dialectical behavioral therapy (DBT), and interpersonal therapy (IPT), have shown success in the treatment of binge eating disorder [41,42]. Some have argued that the utility of these psychotherapeutic modalities in treating food addictions negates the idea of food as addictive and, therefore, nullifies the utility of pharmacotherapy targeting reward circuitry [4345]. However, drug addictions are accepted as dysfunctions in the reward processes in the brain, and psychotherapy has been effectively utilized in the treatment of alcohol and narcotic addictions. Thus, the utility of therapy does not preclude the usefulness of pharmaceutical interventions aimed at addressing underlying brain dysfunction in food-addicted individuals. Some even have argued that obesity would best be understood as an impulse-control disorder, thereby requiring multimodal treatment to achieve success [46,47].

Psychotherapy also might help to address co-morbid psychiatric disorders that could be contributing to dysfunctional eating behaviors. For some, eating may have become an ingrained behavior that serves as a form of self-medication in response to negative emotional states such as depression, anxiety, loneliness, boredom, anger, and interpersonal conflict [4852]. As such, the use of psychotherapy might be beneficial in effecting underlying psychopathology that may be, at least in part, driving the food addiction. If so, the role of behavior modification can be highlighted in conjunction with pharmacological interventions, for the treatment of food addictions. Thus, the need for multimodal treatment paradigms is underscored [53]. It should also be noted, however, that treatment of disordered eating can be a long and arduous process marked by alternating periods of relapse and recovery.

Because there are many studies that have established the role of dopaminergic genetics in binge eating and obesity in general, along with other notable brain substances and peptides, including leptin [54,55], pharmacological treatments also are considered adjunctive avenues of treatment (as discussed later).


Given the high rates of relapse and limited efficacy of current obesity treatments, increasing numbers of obese individuals find themselves turning to bariatric surgery for treatment of obesity [56]. Initial weight-loss reported with this procedure is excellent, averaging 88 lbs [57]. Complication rates from this procedure, however, are high, ranging from 20–30%, as well as causing long-term health effects and nutrient deficiencies [5860]. Also, similar to behavioral interventions, relapse rates are high ranging from 20.4–34.9% [61]. Further, there have been reports of a subset of bariatric surgical patients who, being less able to consume food in excess, later developed other addictive behaviors such as gambling, substance abuse, and impulsive spending [62,63], suggesting the addictive phenotype may be hard-wired in some cases of obesity.

Other surgical modalities have been investigated as possible means of treating obesity. It has long been known that lesions in the ventromedial hypothalamus produced obesity [6468]. Scientists therefore attempted to use deep brain stimulation on this portion on the brain as a means of weight loss. Initial trials with nonhuman animals had seemed promising [6973], but the translation to humans was more troublesome, with patients having regained all initial weight-loss by one year post-surgery [7477]. To address these issues, neurosurgeons have discussed the possibility of instead targeting areas involved in other areas of the reward circuitry rather than the hypothalamus itself [78]. Specifically, interest has been expressed in targeting the nucleus accumbens, subgenual cingulate cortex, anterior insula, amygdala, and stria terminalis as potential locations for deep brain stimulation [78].

Given the current lack of long-term benefit, cost, and the significant risks, at this time, surgery is not an optimal treatment for food-addicted patients. Despite the type of surgery undertaken, in desperation for results, obese patients often undergo these expensive, invasive procedures with high complication rates, long-term health impacts, and with high relapse rates, a far from ideal treatment. As a result, much attention today has shifted to developing better treatment options. Given the rise of obesity not only in the United States, but around the world [79], a number of pharmaceutical companies are looking to develop new treatments for obesity based upon knowledge about the addiction hypothesis [16] and Reward Deficiency Syndrome (RDS) [27].


The American Society of Addiction Medicine (ASAM) now recognizes addictions as a brain disorder [80], and as such, treatments aimed at addressing food addiction must address the dysfunctions at the level of the brain. It follows, then, that pharmaceuticals may be essential adjuncts to effective treatment of these disordered brain mechanisms. A number of excellent reviews have been written outlining the endogenous neurotransmitter involvement in food addicts, including papers on opiates [81,82], neuropeptide Y and leptin [83], cannabinoids [84], and dopamine [13,85,86]. Unsurprisingly, the use of pharmaceuticals has been suggested to modulate these brain areas, decrease craving, and negate pathologic drive for overconsumption [87,88].

Current pharmacologic treatments for obesity have failed to adequately address the problem. Despite the neurobiological linkage with satiety signals and noted elevated levels of leptin in obese individuals and food addicts, trials of pegylated recombinant human leptin targeting the homeostatic mechanisms of obesity have not succeeded [64,83,8993]. Silbutramine, a mixed serotonin, norepinephrine, and dopamine reuptake inhibitor, had shown some promise of effecting weight loss, but was pulled off the market in 2010 due to concerns of increased risk of stroke and cardiovascular events [94,95]. Orlistat is currently the only pharmacologic therapy for obesity that is approved for long-term use (up to one year). It works by inhibiting absorption of fat in the gut and results in modest weight loss of an average of 6.4 pounds in the course of a year [94]. Phentermine and diethylpropion also are commonly provided for obesity, and similarly have had limited success [96]. Despite their use, these pharmaceuticals for obesity have failed to produce significant, enduring weight loss [97] and at best have provided only modest, short-term benefit [98].

Given the lack of utility of current treatments, new modalities currently are under investigation. Traditionally, obesity-related treatments have targeted hunger and eating behavior itself. Researchers now are interested in further characterizing the effects of various nutrients on the neurotransmitter systems of the brain, as these may provide for targeted interventions based on an individual’s particular food preference [4]. Researchers also are interested in pharmacotherapeutic interventions aimed at reducing the reinforcing effects of highly palatable nutrients as a means of reducing body mass [15]. Indeed, a number of new treatments are in both Phase II and Phase III clinical trials, including: Contrave, Qnexa, and Lorcaserin, as well as investigating other novel pharmaceuticals [16]. The majority of these potential treatment options target the neuropathways and neurotransmitters discussed individually below [99].


Dopaminergic dysfunction is a common link between obesity and addiction. Obese individuals and those addicted to substances of abuse have decreased dopamine receptor D2 availability in the striatum of the brain [11,100]. In obese individuals, this level of decrease is proportional to the body mass index [87], which makes intuitive sense in a case of food addictions, as dopamine is the primary reward transmitter in the brain’s reward circuitry [101]. Therefore, it has been postulated that food-addicted individuals are driven to eat either because they obtain a very high reward from the food itself (too much dopamine) or because they are not satisfied by normal amounts of food (too little dopamine) [9,32,78]. Thus, pharmaceuticals both targeting and inhibiting dopaminergic pathways are currently under investigation, including: raclopride, buprprion, and antipsychotics [102]. However, blocking dopaminergic function has met with enhanced suicide ideation as reviewed and rejected by the FDA when considering aproval of rimonabant [103,104].

Endorphins (endogenous opioid peptides that function as neurotransmitters)

Opioids have long been implicated in the reward circuitry of the brain and with pleasure derived from eating. As such, opioid antagonists have been shown to decrease short-term food intake and decrease the pleasurable nature of palatable foods, and have been long considered in weight loss therapy [105]. Studies suggest that opioid antagonists such as naloxone, naltrexone, and nalmefene may result in decreased caloric intake and thus have been suggested for use [106119]. However, the results of clinical trials have been mixed, with a few suggesting that opioid antagonists failed to yield any significant effect in the treatment of obese binge eaters [120,121]. It has been suggested that these differences in findings may be explained by such things as varying dosing strategies, open-label vs. blind designs, and use of antagonists as a sole agent vs. augmentation strategy [122]. Given these findings, a double-blind placebo controlled dose-response trial in food addictions seems a logical future direction for this work. The use of agents that block opiate receptors (e.g., mu opiate receptor) may be helpful in the short term, however, caution for long-term use seems prudent, based on many studies [123].


Cravings may serve as an obstacle to treatment and may be controlled through serotonergic and dopaminergic agonists [124]. Similar to drug addicted persons, people with food addiction may also experience overpowering urges to eat specific foods, better known as cravings [125], especially in environments of dietary restrictions such as found in repetitive diets [126]. Unsurprisingly, food cravings have been implicated in snacking behavior, compliance with dietary restrictions, early dropout from weight-loss treatments, and overeating and bingeing in obese individuals [127129]. It is these compulsive behaviors that serotonergic drugs are thought to modulate [130,131]. Thus, it likely comes as no surprise that various serotonergic drugs are under investigation as possible treatments for binge eating and food addiction, including fluoxetine, sertraline, sibutramine, fluvoxamine, desipramine, imipramine, and topiramate, with results demonstrating superiority of serotonergic drugs to placebo [132].

Glutamate and GABA

Increasing numbers of studies have also implicated the glutamate system in the regulation of food intake [133,134], as well as drug and alcohol abuse [135,136]. It has thus been hypothesized that compounds that decrease the function of the glutamate system may reduce food intake [137,138] As such, compounds such as acamprosate, an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor and possible partial antagonist of mGluR5 function [139] has long been used in the maintenance of alcohol dependence under the presumed action that it decreases cravings [140,141], and is being looked at as a potential medication in binge eating and food addictions as well [142145]. It has been reported that acamprosate can reduce food cravings and associated weight gain in alcoholic patients [146], but results have been mixed as a standalone in binge eating disorder [147]. Similarly, topiramate, an antagonist of the glutamate kainate receptor has shown promise in addressing bulimia nervosa, binge eating disorder, as well as alcoholism [137,138,148150]. Memantine, another NMDA antagonist, has been shown to reduce the consumption of highly palatable food [151] and has been shown to reduce binge eating in open-label trails [152,153]. Additionally, the mGluR5 antagonist MTEP has been shown to reduce binge eating [151]. Baclofen also is under investigation as a possible GABAnergic intervention [102]. There also are a number of GABAnergic drugs under investigation for various drug addictions that may in the future be tested in food addictions; however, their use has been questioned [154].


Cannabinoid receptors may serve as another potential target. Antagonism of the endocannabinoid receptors, specifically CB1 and CB2, has been suggested as a potential target in the battle against obesity. CB1 receptors are associated with motivational brain reward circuits involving the mesocorticolimbic dopamine system [155157], and CB-1 receptor antagonism is believed to attenuate dopaminergic activation of the reward circuitry [158]. Given this correlation, it follows that much research has been aimed at the development of novel synthetic CB-1 receptor antagonists, as this is believed to have appetitive component [159,160]. The most famous example, rimonabant, a selective cannabinoid-1 receptor antagonist and CB-1 receptor inverse agonist, had shown promise resulting in an average drop of 11 pounds over the course of a year [94,161]. However, it was removed from the market in 2007 due to increased reports of anxiety, depression, aggression, psychosis, and increased suicidal thinking [162]. Nevertheless, there are other cannabinoid drugs currently under investigation including: dronabinol, nabilone, sativex, levonantradol, WIN55212-2, AM 251, AM4113, SR141716A, V24343, SR-147778, SLV319, MK-0364, and CP-945, 598 [102,163166]. Of these, nabilone, SR141716A, AM4113, V24343, SR-147778, SLV319, MK-0364, and CP-945,598 have been specifically targeted for obesity related issues [163,164,167].

As originally noted in 1948, addicts typically are able to function without symptoms of withdrawal and craving in an environment devoid of the substance to which the person is addicted, but upon returning to the environment associated with these addictive behaviors, the addict experiences marked feelings of withdrawal and craving [168]. Similar to drug cravings, food cravings can easily be triggered by exposure to sight, smell, or imagery of the craved food [169]. Given these trends, it is time to address some of the cultural aspects associated with these behaviors.


As it stands, obesity and binge eating behaviors will continue to be a threat to global heath [170]. Therefore, it is essential to reevaluate the current food environment from many aspects, while taking into consideration both the individual’s perspective and society as whole. Societal measures may, in fact, be required at this time, as dysfunctional eating behaviors affect not only the current generation, but also its offspring due to the effects that consuming certain highly palatable foods may have on the developing brain in utero.

Given that cultural influences often are driven by economic factors that lie outside the control of the individual, the topic of obesity cannot simply be relegated to the domain of personal responsibility. Rather, economic incentives that encourage people to make unhealthy food choices need to be re-evaluated on a larger scale. Indeed, any plan to combat the rise in obesity will need to address the economic, political, social, psychological, and biological factors that contribute to obesity, as well as factors such as taste, accessibility, convenience, cost, and level of promotion [79]. Moreover, it is important to closely re-evaluate the current state of food marketing. One study has found that food-addicted persons respond at an even higher level to food cues than their non-addicted counterparts [171]. This finding suggests that advertising cues may contribute, at least in part, to compulsive eating in at-risk persons. Further, societal changes such as reevaluating where government subsidies are allocated, taxation, publicly enforced well-care programs, and corporate driven employee well-being programs also may be needed to address the issues of disordered eating and obesity. While these efforts are not expected to cure obesity, binge eating, or food addiction, they may help to reduce their prevalence and aid prevention efforts.

Undertaking such actions as advertising, availability, and addressing public health and cost-related measures are not unreasonable. Indeed, each of these efforts has been used successfully in reducing alcohol and tobacco use [15]. Given the implications of obesity and the underlying cost in terms of health care dollars and human health, the utility of these efforts to reduce the rates of obesity would be profound [15]. Indeed, many researchers have argued the only realistic means of addressing this epidemic would be refocusing efforts on prevention, as well as changes in public health policy [172175].


Recent research has uncovered both neurobiological and behavioral similarities between substance dependence and excess consumption of highly processed foods [18]. Observations of this nature have led some to propose the concept term food addiction and to postulate its role in the obesity epidemic. A better understanding of the food addiction paradigm and the underlying brain dysfunction may help develop better pharmaceutical therapies. There are a number of such therapies under investigation targeting neuropathways and neurotransmitters implicated in addiction, including: dopaminergic, opioid, GABAnergic, cannabinoid, serotonergic, and other novel treatment options.

However, these medications are not without risk; many carry significant side effects including increased risk for depression, anxiety, obsessive-compulsive disorder, seizures, suicide, confusion, or memory deficits [16]. Given the risks and side effects associated with these drugs, physicians need to exercise great care when considering whether to prescribe them as treatments, and to carefully select their population base prior to prescribing [16]. One alternative that offers new hope following additional rigorous research, is to consider gentle activation of dopamine D2 receptors, preventing dopamine D2 receptor down regulation [18,176].


The writing of this paper was supported in part by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01-AA07112 and K05-AA00219, and the Medical Research Service of the U.S Department of Veterans Affairs to Dr. Marlene Oscar Berman. Dr. Nicole Avena is the recipient of NIDA grant number K01DA031230-02. Kenneth Blum, PhD is the recipient of a grant awarded by Life Extension Foundation in behalf of Path Foundation, NY, New York City. The authors appreciate the editorial work of Paula Edge and Margaret A. Madigan.


American Society of Addiction Medicine
Cognitive Behavioral Therapy (CBT)
Cognitive Behavioral Therapy guided self-help (CBT-gsh)
dialectical DBT
Dialectical Behavioral Therapy
Interpersonal Therapy
Reward Deficiency Syndrome


This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Conflict of Interest

Kenneth Blum, PhD, has been awarded a number of global patents for Obesity treatment compounds. Mark Gold, MD, has US patents pending related to obesity treatment compounds. No other author has any conflict to report.


1. Sturm R. The effects of obesity, smoking, and drinking on medical problems and costs. Health Aff (Millwood) 2002;21:245–253. [PubMed]
2. Skidmore PM, Yarnell JW. The obesity epidemic: prospects for prevention. QJM. 2004;97:817–825. [PubMed]
3. NIDDK. Overweight and Obesity Statistics WIN: Weight-control Information Network. 2005.
4. Avena NM, Gold MS. Food and addiction - sugars, fats and hedonic overeating. Addiction. 2011;106:1214–1215. [PubMed]
5. Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32:20–39. [PMC free article] [PubMed]
6. Avena NM, Rada P, Hoebel BG. Sugar and fat bingeing have notable differences in addictive-like behavior. J Nutr. 2009;139:623–628. [PubMed]
7. Colantuoni C, Rada P, McCarthy J, Patten C, Avena NM, et al. Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obes Res. 2002;10:478–488. [PubMed]
8. Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13:635–641. [PMC free article] [PubMed]
9. Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010;30:13105–13109. [PMC free article] [PubMed]
10. Gearhardt AN, Corbin WR, Brownell KD. Preliminary validation of the Yale Food Addiction Scale. Appetite. 2009;52:430–436. [PubMed]
11. Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. 2008;363:3191–3200. [PMC free article] [PubMed]
12. Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci. 2011;15:37–46. [PMC free article] [PubMed]
13. Blum K, Liu Y, Shriner R, Gold MS. Reward circuitry dopaminergic activation regulates food and drug craving behavior. Curr Pharm Des. 2011;17:1158–1167. [PubMed]
14. Erlanson-Albertsson C. Appetite regulation and energy balance. Acta Paediatr Suppl. 2005;94:40–41. [PubMed]
15. Avena NM, Gold MS. Variety and hyperpalatability: are they promoting addictive overeating? Am J Clin Nutr. 2011;94:367–368. [PubMed]
16. Blumenthal DM, Gold MS. Neurobiology of food addiction. Curr Opin Clin Nutr Metab Care. 2010;13:359–365. [PubMed]
17. Leibowitz SF, Hoebel BG. Behavioral neuroscience and obesity. In: Bray GBC, James P, editors. The Handbook of Obesity. New York: Marcel Dekker; 2004. pp. 301–371.
18. Blum K, Oscar-Berman M, Barh D, Giordano J, Gold M. Dopamine Genetics and Function in Food and Substance Abuse. J Genet Syndr Gene Ther. 2013:4. [PMC free article] [PubMed]
19. Berner LA, Bocarsly ME, Hoebel BG, Avena NM. Baclofen suppresses binge eating of pure fat but not a sugar-rich or sweet-fat diet. Behav Pharmacol. 2009;20:631–634. [PMC free article] [PubMed]
20. Corwin RL, Wojnicki FH. Baclofen, raclopride, and naltrexone differentially affect intake of fat and sucrose under limited access conditions. Behav Pharmacol. 2009;20:537–548. [PubMed]
21. Volkow ND, Wise RA. How can drug addiction help us understand obesity? Nat Neurosci. 2005;8:555–560. [PubMed]
22. MASLOW A. A preface to motivation theory. Psychosomatic medicine. 1943;5:85–92.
23. Phillips WJ. Starvation and survival: some military considerations. Mil Med. 1994;159:513–516. [PubMed]
24. Fessler DM. The implications of starvation induced psychological changes for the ethical treatment of hunger strikers. J Med Ethics. 2003;29:243–247. [PMC free article] [PubMed]
25. Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating. Neuron. 2002;36:199–211. [PubMed]
26. Stice E, Yokum S, Zald D, Dagher A. Dopamine-based reward circuitry responsivity, genetics, and overeating. Curr Top Behav Neurosci. 2011;6:81–93. [PubMed]
27. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, et al. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996;89:396–400. [PMC free article] [PubMed]
28. Comings DE, Flanagan SD, Dietz G, Muhleman D, Knell E, et al. The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol. 1993;50:176–185. [PubMed]
29. Noble EP, Noble RE, Ritchie T, Syndulko K, Bohlman MC, et al. D2 dopamine receptor gene and obesity. Int J Eat Disord. 1994;15:205–217. [PubMed]
30. Roberts AJ, Koob GF. The neurobiology of addiction: an overview. Alcohol Health Res World. 1997;21:101–106. [PubMed]
31. Davis CL, Tomporowski PD, Boyle CA, Waller JL, Miller PH, et al. Effects of aerobic exercise on overweight children’s cognitive functioning: a randomized controlled trial. Res Q Exerc Sport. 2007;78:510–519. [PMC free article] [PubMed]
32. Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008;322:449–452. [PMC free article] [PubMed]
33. Chen AL, Blum K, Chen TJ, Giordano J, Downs BW, et al. Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. Food Funct. 2012;3:40–48. [PubMed]
34. Devlin MJ. Is there a place for obesity in DSM-V? Int J Eat Disord. 2007;40(Suppl):S83–S88. [PubMed]
35. Volkow ND, O’Brien CP. Issues for DSM-V: should obesity be included as a brain disorder? Am J Psychiatry. 2007;164:708–710. [PubMed]
36. Jeffery RW, Drewnowski A, Epstein LH, Stunkard AJ, Wilson GT, et al. Long-term maintenance of weight loss: current status. Health Psychol. 2000;19:5–16. [PubMed]
37. Wadden TA, Butryn ML, Byrne KJ. Efficacy of lifestyle modification for long-term weight control. Obes Res. 2004;12:151S–162S. [PubMed]
38. Diabetes Prevention Program Research Group. Knowler WC, Fowler SE, Hamman RF, Christophi CA, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–1686. [PMC free article] [PubMed]
39. Brownell KD. The humbling experience of treating obesity: Should we persist or desist? Behav Res Ther. 2010;48:717–719. [PubMed]
40. Epstein LH, Dearing KK, Temple JL, Cavanaugh MD. Food reinforcement and impulsivity in overweight children and their parents. Eat Behav. 2008;9:319–327. [PubMed]
41. Iacovino JM, Gredysa DM, Altman M, Wilfley DE. Psychological treatments for binge eating disorder. Curr Psychiatry Rep. 2012;14:432–446. [PMC free article] [PubMed]
42. Devlin MJ, Goldfein JA, Petkova E, Jiang H, Raizman PS, et al. Cognitive behavioral therapy and fluoxetine as adjuncts to group behavioral therapy for binge eating disorder. Obes Res. 2005;13:1077–1088. [PubMed]
43. NICE. Eating disorders - Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa, and related eating disorders (Clinical Guideline No. 9) 2004. [PubMed]
44. Wilson GT, GRILO CM, VITOUSEK KM. Psychological treatment of eating disorders. The American psychologist. 2007;62:199–216. [PubMed]
45. Wilson GT. Eating disorders, obesity and addiction. European eating disorders review : the journal of the Eating Disorders Association. 2010;18:341–351. [PubMed]
46. Vaidya VM, Malik SV, Kaur S, Kumar S, Barbuddhe SB. Comparison of PCR, immunofluorescence assay, and pathogen isolation for diagnosis of q fever in humans with spontaneous abortions. Journal of clinical microbiology. 2008;46:2038–2044. [PMC free article] [PubMed]
47. Vanbuskirk KA, Potenza MN. The Treatment of Obesity and Its Cooccurrence with Substance Use Disorders. Journal of addiction medicine. 2010;4:1–10. [PMC free article] [PubMed]
48. Mcelroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE, et al. Are mood disorders and obesity related? Reviews for the mental health professional. The Journal of clinical psychiatry. 2004;65:634–651. [PubMed]
49. Goldbacher EM, Matthews KA. Are psychological characteristics related to risk of the metabolic syndrome? A review of the literature. Ann Behav Med. 2007;34:240–252. [PubMed]
50. Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62:321–326. [PubMed]
51. Gariepy G, Nitka D, Schmitz N. The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. Int J Obes (Lond) 2010;34:407–419. [PubMed]
52. Marijnissen RM, Bus BA, Holewijn S, Franke B, Purandare N, et al. Depressive symptom clusters are differentially associated with general and visceral obesity. J Am Geriatr Soc. 2011;59:67–72. [PubMed]
53. Taylor VH, Curtis CM, Davis C. The obesity epidemic: the role of addiction. CMAJ. 2010;182:327–328. [PMC free article] [PubMed]
54. Monteleone P, Maj M. Dysfunctions of leptin, ghrelin, BDNF and endocannabinoids in eating disorders: beyond the homeostatic control of food intake. Psychoneuroendocrinology. 2013;38:312–330. [PubMed]
55. Davis C, Levitan RD, Yilmaz Z, Kaplan AS, Carter JC, et al. Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes. Prog Neuropsychopharmacol Biol Psychiatry. 2012;38:328–335. [PubMed]
56. NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991;115:956–961. [PubMed]
57. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–1737. [PubMed]
58. Pisapia JM, Halpern CH, Williams NN, Wadden TA, Baltuch GH, et al. Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study. Neurosurg Focus. 2010;29:E15. [PubMed]
59. Bal B, Koch TR, Finelli FC, Sarr MG. Managing medical and surgical disorders after divided Roux-en-Y gastric bypass surgery. Nat Rev Gastroenterol Hepatol. 2010;7:320–334. [PubMed]
60. Nakamura M, Yazaki M, Kobayashi Y, Fukushima K, Ikeda S, et al. The characteristics of food intake in patients with type II citrullinemia. J Nutr Sci Vitaminol (Tokyo) 2011;57:239–245. [PubMed]
61. Christou NV, Look D, Maclean LD. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Ann Surg. 2006;244:734–740. [PubMed]
62. Wendling A, Wudyka A. Narcotic addiction following gastric bypass surgery--a case study. Obes Surg. 2011;21:680–683. [PubMed]
63. Conason A, Teixeira J, Hsu CH, Puma L, Knafo D, et al. Substance Use Following Bariatric Weight Loss Surgery. Arch Surg. 2012 [PubMed]
64. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 1999;22:221–232. [PubMed]
65. King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006;87:221–244. [PubMed]
66. Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. Anat Rec. 1940;78:149–172.
67. ANAND BK, BROBECK JR. Localization of a “feeding center“ in the hypothalamus of the rat. Proc Soc Exp Biol Med. 1951;77:323–324. [PubMed]
68. Gold RM. Hypothalamic obesity: the myth of the ventromedial nucleus. Science. 1973;182:488–490. [PubMed]
69. Herberg LJ, Blundell JE. Lateral hypothalamus: hoarding behavior elicited by electrical stimulation. Science. 1967;155:349–350. [PubMed]
70. Stenger J, Fournier T, Bielajew C. The effects of chronic ventromedial hypothalamic stimulation on weight gain in rats. Physiol Behav. 1991;50:1209–1213. [PubMed]
71. Brown FD, Fessler RG, Rachlin JR, Mullan S. Changes in food intake with electrical stimulation of the ventromedial hypothalamus in dogs. J Neurosurg. 1984;60:1253–1257. [PubMed]
72. Takaki A, Aou S, Oomura Y, Okada E, Hori T. Feeding suppression elicited by electrical and chemical stimulations of monkey hypothalamus. Am J Physiol. 1992;262:R586–R594. [PubMed]
73. Sani S, Jobe K, Smith A, Kordower JH, Bakay RA. Deep brain stimulation for treatment of obesity in rats. J Neurosurg. 2007;107:809–813. [PubMed]
74. Quaade F. Letter: Stereotaxy for obesity. Lancet. 1974;1:267. [PubMed]
75. Quaade F, Vaernet K, Larsson S. Stereotaxic stimulation and electrocoagulation of the lateral hypothalamus in obese humans. Acta Neurochir (Wien) 1974;30:111–117. [PubMed]
76. Hamani C, McAndrews MP, Cohn M, Oh M, Zumsteg D, et al. Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann Neurol. 2008;63:119–123. [PubMed]
77. Wilent WB, Oh MY, Buetefisch CM, Bailes JE, Cantella D, et al. Induction of panic attack by stimulation of the ventromedial hypothalamus. J Neurosurg. 2010;112:1295–1298. [PubMed]
78. Taghva A, Corrigan JD, Rezai AR. Obesity and brain addiction circuitry: implications for deep brain stimulation. Neurosurgery. 2012;71:224–238. [PubMed]
79. Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med. 2006;12:62–66. [PubMed]
80. Smith DE. The process addictions and the new ASAM definition of addiction. J Psychoactive Drugs. 2012;44:1–4. [PubMed]
81. Grigson PS. Like drugs for chocolate: separate rewards modulated by common mechanisms? Physiol Behav. 2002;76:389–395. [PubMed]
82. Kelley AE, Bakshi VP, Haber SN, Steininger TL, Will MJ, et al. Opioid modulation of taste hedonics within the ventral striatum. Physiol Behav. 2002;76:365–377. [PubMed]
83. Kalra SP, Kalra PS. Overlapping and interactive pathways regulating appetite and craving. J Addict Dis. 2004;23:5–21. [PubMed]
84. Harrold JA, Williams G. The cannabinoid system: a role in both the homeostatic and hedonic control of eating? Br J Nutr. 2003;90:729–734. [PubMed]
85. Cannon CM, Bseikri MR. Is dopamine required for natural reward? Physiol Behav. 2004;81:741–748. [PubMed]
86. Carr KD. Augmentation of drug reward by chronic food restriction: behavioral evidence and underlying mechanisms. Physiol Behav. 2002;76:353–364. [PubMed]
87. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, et al. Brain dopamine and obesity. Lancet. 2001;357:354–357. [PubMed]
88. Volkow ND, O’Brien CP. Issues for DSM-V: should obesity be included as a brain disorder? Am J Psychiatry. 2007;164:708–710. [PubMed]
89. Kleinridders A, Könner AC, Brüning JC. CNS-targets in control of energy and glucose homeostasis. Curr Opin Pharmacol. 2009;9:794–804. [PubMed]
90. Hukshorn CJ, Van Dielen FM, Buurman WA, Westerterp-Plantenga MS, Campfield LA, et al. The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects. International journal of obesity and related metabolic disorders. 2002;26:504–509. [PubMed]
91. Neary NM, McGowan BM, Monteiro MP, Jesudason DR, Ghatei MA, et al. No evidence of an additive inhibitory feeding effect following PP and PYY 3–36 administration. Int J Obes (Lond) 2008;32:1438–1440. [PubMed]
92. Kreier F. To be, or not to be obese - that’s the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences. Med Hypotheses. 2010;75:214–217. [PubMed]
93. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432. [PubMed]
94. Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335:1194–1199. [PMC free article] [PubMed]
95. Pollack A. Abbott Labs withdraws Meridia from the market. New York: New York Times; 2010.
96. Powell AG, Apovian CM, Aronne LJ. New drug targets for the treatment of obesity. Clin Pharmacol Ther. 2011;90:40–51. [PubMed]
97. Yanovski SZ. Pharmacotherapy for obesity--promise and uncertainty. N Engl J Med. 2005;353:2187–2189. [PubMed]
98. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med. 2005;353:2111–2120. [PubMed]
99. Berner LA, Bocarsly ME, Hoebel BG, Avena NM. Pharmacological interventions for binge eating: lessons from animal models, current treatments, and future directions. Curr Pharm Des. 2011;17:1180–1187. [PubMed]
100. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Archives of general psychiatry. 1991;48:648–654. [PubMed]
101. Kirsch P, Reuter M, Mier D, Lonsdorf T, Stark R, et al. Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward. Neurosci Lett. 2006;405:196–201. [PubMed]
102. Berner LA, Bocarsly ME, Hoebel BG, Avena NM. Pharmacological interventions for binge eating: lessons from animal models, current treatments, and future directions. Curr Pharm Des. 2011;17:1180–1187. [PubMed]
103. Bellocchio L, Soria-Gómez E, Quarta C, Metna-Laurent M, Cardinal P, et al. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade. Proc Natl Acad Sci U S A. 2013;110:4786–4791. [PubMed]
104. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370:1706–1713. [PubMed]
105. Cota D, Tschöp MH, Horvath TL, Levine AS. Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev. 2006;51:85–107. [PubMed]
106. Thompson DA, Welle SL, Lilavivat U, Penicaud L, Campbell RG. Opiate receptor blockade in man reduces 2-deoxy-D-glucose-induced food intake but not hunger, thirst, and hypothermia. Life sciences. 1982;31:847–852. [PubMed]
107. Trenchard E, Silverstone T. Naloxone reduces the food intake of normal human volunteers. Appetite. 1983;4:43–50. [PubMed]
108. Cohen MR, Cohen RM, Pickar D, Murphy DL. Naloxone reduces food intake in humans. Psychosom Med. 1985;47:132–138. [PubMed]
109. Drewnowski A, Krahn DD, Demitrack MA, Nairn K, Gosnell BA. Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement. Physiol Behav. 1992;51:371–379. [PubMed]
110. MacIntosh CG, Sheehan J, Davani N, Morley JE, Horowitz M, et al. Effects of aging on the opioid modulation of feeding in humans. J Am Geriatr Soc. 2001;49:1518–1524. [PubMed]
111. Fantino M, Hosotte J, Apfelbaum M. An opioid antagonist, naltrexone, reduces preference for sucrose in humans. Am J Physiol. 1986;251:R91–R96. [PubMed]
112. Jonas JM, Gold MS. Naltrexone reverses bulimic symptoms. Lancet. 1986;1:807. [PubMed]
113. Melchior JC, Fantino M, Rozen R, Igoin L, Rigaud D, et al. Effects of a low dose of naltrexone on glucose-induced allesthesia and hunger in humans. Pharmacol Biochem Behav. 1989;32:117–121. [PubMed]
114. Bertino M, Beauchamp GK, Engelman K. Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. Am J Physiol. 1991;261:R59–R63. [PubMed]
115. Chatoor I, Herman BH, Hartzler J. Effects of the opiate antagonist, naltrexone, on binging antecedents and plasma beta-endorphin concentrations. Journal of the American Academy of Child and Adolescent Psychiatry. 1994;33:748–752. [PubMed]
116. Yeomans MR, Gray RW. Selective effects of naltrexone on food pleasantness and intake. Physiol Behav. 1996;60:439–446. [PubMed]
117. Yeomans MR, Gray RW. Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect. Physiol Behav. 1997;62:15–21. [PubMed]
118. Yeomans MR, Wright P, Macleod HA, Critchley JA. Effects of nalmefene on feeding in humans. Dissociation of hunger and palatability. Psychopharmacology (Berl) 1990;100:426–432. [PubMed]
119. Yeomans MR, Wright P. Lower pleasantness of palatable foods in nalmefene-treated human volunteers. Appetite. 1991;16:249–259. [PubMed]
120. Mitchell JE, Christenson G, Jennings J, Huber M, Thomas B, et al. A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia. Journal of clinical psychopharmacology. 1989;9:94–97. [PubMed]
121. Alger SA, Schwalberg MJ, Bigaouette JM, Howard LJ, Reid LD. Using drugs to manage binge-eating among obese and normal weight patients (Reid LD Edn) Opioids, bulimia, and alcohol abuse and alcoholism. New York: Springer-Verlag; 1991. pp. 131–142.
122. Elman I, Borsook D, Lukas SE. Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2006;31:2091–2120. [PubMed]
123. Blum K, Chen AL, Chen TJ, Braverman ER, Reinking J, et al. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary. Theoretical biology & medical modelling. 2008;5:24. [PMC free article] [PubMed]
124. Rothman RB, Blough BE, Baumann MH. Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions. AAPS J. 2007;9:E1–E10. [PMC free article] [PubMed]
125. Rabinovitz S. Stress and Food Craving. In: Yehuda S, Mostofsky D, editors. Nutrients, Stress, and Medical Disorders. New Jersey: Humana Press; 2006. pp. 155–164.
126. Kamen JM, Peryan DR. Acceptability of repetitive diets. Food Technology. 1961;15:173–177.
127. Basdevant A, Craplet C, Guy-Grand B. Snacking patterns in obese French women. Appetite. 1993;21:17–23. [PubMed]
128. Drewnowski A, Kurth CL, Rahaim JE. Taste preferences in human obesity: environmental and familial factors. Am J Clin Nutr. 1991;54:635–641. [PubMed]
129. Gendall KA, Sullivan PF, Joyce PR, Fear JL, Bulik CM. Psychopathology and personality of young women who experience food cravings. Addict Behav. 1997;22:545–555. [PubMed]
130. Fluoxetine Bulimia Nervosa Collaborative Study Group. Fluoxetine in the treatment of bulimia nervosa. A multicenter, placebo-controlled, double-blind trial. Archives of general psychiatry. 1992;49:139–147. [PubMed]
131. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995;4(3 Suppl):477S–480S. [PubMed]
132. Walsh BT, Wilson GT, Loeb KL, Devlin MJ, Pike KM, et al. Medication and psychotherapy in the treatment of bulimia nervosa. Am J Psychiatry. 1997;154:523–531. [PubMed]
133. Stanley BG, Willett VL, 3rd, Donias HW, Dee MG, 2nd, Duva MA. Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control. Am J Physiol. 1996;270:R443–R449. [PubMed]
134. Meister B. Neurotransmitters in key neurons of the hypothalamus that regulate feeding behavior and body weight. Physiol Behav. 2007;92:263–271. [PubMed]
135. Gass JT, Olive MF. Glutamatergic substrates of drug addiction and alcoholism. Biochem Pharmacol. 2008;75:218–265. [PMC free article] [PubMed]
136. Kalivas PW, Lalumiere RT, Knackstedt L, Shen H. Glutamate transmission in addiction. Neuropharmacology. 2009;56:169–173. [PMC free article] [PubMed]
137. McElroy SL, Arnold LM, Shapira NA, Keck PE, Jr, Rosenthal NR, et al. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry. 2003;160:255–261. [PubMed]
138. McElroy SL, Hudson JI, Capece JA, Beyers K, Fisher AC, et al. Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study. Biol Psychiatry. 2007;61:1039–1048. [PubMed]
139. Blednov YA, Harris RA. Metabotropic glutamate receptor 5 (mGluR5) regulation of ethanol sedation, dependence and consumption: relationship to acamprosate actions. Int J Neuropsychopharmacol. 2008;11:775–793. [PMC free article] [PubMed]
140. Mann K, Lehert P, Morgan MY. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcoholism, clinical and experimental research. 2004;28:51–63. [PubMed]
141. Mann K, Kiefer F, Spanagel R, Littleton J. Acamprosate: recent findings and future research directions. Alcohol Clin Exp Res. 2008;32:1105–1110. [PubMed]
142. Avena NM. Examining the addictive-like properties of binge eating using an animal model of sugar dependence. Exp Clin Psychopharmacol. 2007;15:481–491. [PubMed]
143. Davis C, Carter JC. Compulsive overeating as an addiction disorder. A review of theory and evidence. Appetite. 2009;53:1–8. [PubMed]
144. Root TL, Pisetsky EM, Thornton L, Lichtenstein P, Pedersen NL, et al. Patterns of co-morbidity of eating disorders and substance use in Swedish females. Psychol Med. 2010;40:105–115. [PMC free article] [PubMed]
145. Calero-Elvira A, Krug I, Davis K, López C, Fernández-Aranda F, et al. Meta-analysis on drugs in people with eating disorders. Eur Eat Disord Rev. 2009;17:243–259. [PubMed]
146. Han DH, Lyool IK, Sung YH, Lee SH, Renshaw PF. The effect of acamprosate on alcohol and food craving in patients with alcohol dependence. Drug Alcohol Depend. 2008;93:279–283. [PubMed]
147. McElroy SL, Guerdjikova AI, Winstanley EL, O’Melia AM, Mori N, et al. Acamprosate in the treatment of binge eating disorder: a placebo-controlled trial. Int J Eat Disord. 2011;44:81–90. [PubMed]
148. Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet. 2003;361:1677–1685. [PubMed]
149. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007;298:1641–1651. [PubMed]
150. Hoopes SP, Reimherr FW, Hedges DW, Rosenthal NR, Kamin M, et al. Treatment of bulimia nervosa with topiramate in a randomized, double-blind, placebo-controlled trial, part 1: improvement in binge and purge measures. The Journal of clinical psychiatry. 2003;64:1335–1341. [PubMed]
151. Bisaga A, Danysz W, Foltin RW. Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder, European neuropsychopharmacology. Eur Neuropsychopharmacol. 2008;18:794–802. [PMC free article] [PubMed]
152. Hermanussen M, Tresguerres JA. A new anti-obesity drug treatment: first clinical evidence that, antagonising glutamate-gated Ca2+ ion channels with memantine normalises binge-eating disorders. Econ Hum Biol. 2005;3:329–337. [PubMed]
153. Brennan BP, Roberts JL, Fogarty KV, Reynolds KA, Jonas JM, et al. Memantine in the treatment of binge eating disorder: an open-label, prospective trial. Int J Eat Disord. 2008;41:520–526. [PubMed]
154. Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, et al. Sex, drugs, and rock ‘n’ roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms. J Psychoactive Drugs. 2012;44:38–55. [PubMed]
155. Pertwee RG. The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond) 2006;30:S13–S18. [PubMed]
156. Demuth DG, Molleman A. Cannabinoid signalling. Life Sci. 2006;78:549–563. [PubMed]
157. Hashimotodani Y, Ohno-Shosaku T, Kano M. Endocannabinoids and synaptic function in the CNS. Neuroscientist. 2007;13:127–137. [PubMed]
158. Pierce RC, Kumaresan V. The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev. 2006;30:215–238. [PubMed]
159. Pavlopoulos S, Thakur GA, Nikas SP, Makriyannis A. Cannabinoid receptors as therapeutic targets. Curr Pharm Des. 2006;12:1751–1769. [PubMed]
160. Tuccinardi T, Ferrarini PL, Manera C, Ortore G, Saccomanni G, et al. Cannabinoid CB2/CB1 selectivity. Receptor modeling and automated docking analysis. J Med Chem. 2006;49:984–994. [PubMed]
161. Curioni C, Andre C. Rimonabant for overweight or obesity. Cochrane database of systematic reviews. 2006:CD006162. [PubMed]
162. SANOFI-AVENTIS. Rimonabant regulatory update in the United States. 2007.
163. Salamone JD, McLaughlin PJ, Sink K, Makriyannis A, Parker LA. Cannabinoid CB1 receptor inverse agonists and neutral antagonists: effects on food intake, food-reinforced behavior and food aversions. Physiol Behav. 2007;91:383–388. [PMC free article] [PubMed]
164. Bellocchio L, Mancini G, Vicennati V, Pasquali R, Pagotto U. Cannabinoid receptors as therapeutic targets for obesity and metabolic diseases. Curr Opin Pharmacol. 2006;6:586–591. [PubMed]
165. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004;3:771–784. [PubMed]
166. Citron ML, Herman TS, Vreeland F, Krasnow SH, Fossieck BE, Jr, et al. Antiemetic efficacy of levonantradol compared to delta-9-tetrahydrocannabinol for chemotherapy-induced nausea and vomiting. Cancer Treat Rep. 1985;69:109–112. [PubMed]
167. Janero DR, Makriyannis A. Targeted modulators of the endogenous cannabinoid system: future medications to treat addiction disorders and obesity. Curr Psychiatry Rep. 2007;9:365–373. [PubMed]
168. Wikler A. Recent progress in research on the neurophysiologic basis of morphine addiction. Am J Psychiatry. 1948;105:329–338. [PubMed]
169. Fedoroff IC, Polivy J, Herman CP. The effect of pre-exposure to food cues on the eating behavior of restrained and unrestrained eaters. Appetite. 1997;28:33–47. [PubMed]
170. Avena NM, Gold JA, Kroll C, Gold MS. Further developments in the neurobiology of food and addiction: update on the state of the science. Nutrition. 2012;28:341–343. [PMC free article] [PubMed]
171. Gearhardt AN, Yokum S, Orr PT, Stice E, Corbin WR, et al. Neural correlates of food addiction. Arch Gen Psychiatry. 2011;68:808–816. [PubMed]
172. Brownell KD. Food fight. New York: McGraw-Hill; 2004.
173. Jeffery RW. Public health approaches to the management of obesity. In: CG Fairburn KDB, editor. Eating disorders and obesity. 2nd edition. New York: Guilford Press; 2002. pp. 613–618.
174. Nestle M, Jacobson MF. Halting the obesity epidemic: a public health policy approach. Public Health Rep. 2000;115:12–24. [PMC free article] [PubMed]
175. Seligman HK, Schillinger D. Hunger and socioeconomic disparities in chronic disease. N Engl J Med. 2010;363:6–9. [PubMed]
176. Blum K, Chen AL, Giordano J, Borsten J, Chen TJ, et al. The addictive brain: all roads lead to dopamine. J Psychoactive Drugs. 2012;44:134–143. [PubMed]