Nicole M. Avena, PhD, is Research Assistant Professor, University of Florida College of Medicine, McKnight Brain Institute, Department of Psychiatry, Gainesville, FL; and Visiting Research Associate, Princeton University, Department of Psychology, Princeton, NJ. Miaoyuan Wang, BA, is second-year medical student, University of Florida College of Medicine, Gainesville, FL; and Mark S. Gold, MD, is Distinguished Professor, Eminent Scholar and Psychiatry Chairman, University of Florida College of Medicine, McKnight Brain Institute, Department of Psychiatry, Gainesville, FL.
Supported by University of Florida, DA-030123-01 (NMA), National Eating Disorders Association. The authors would like to extend their appreciation to Ryan Ramezani and Paula Edge for their assistance preparing this manuscript.
Dr. Avena, Mr. Wang, and Dr. Gold have disclosed no relevant financial relationships.
Address correspondence to: Nicole M. Avena, PhD, University of Florida, College of Medicine, Department of Psychiatry, McKnight Brain Institute; fax: 609-259-3787; email: email@example.com.
There have long been anecdotal accounts of food addiction, but the concept has recently gained scientific validity. Abnormal preoccupation and maladaptive behaviors associated with the procurement and consumption of highly palatable foods has been associated with cases of aberrant eating behaviors, some of which may result in obesity.
Food Addiction in Obesity
In the developed nations, we are struggling to combat obesity, now believed to pose a greater morbidity risk than tobacco use.1 The prevalence of obesity began to increase in the early 1980s; in 1997, the World Health Organization accepted obesity as a major public health problem. By 2005, 23.2% of the world adult population was overweight, and 9.8% were obese. By 2030, these numbers will increase, with an estimated 57.8% of the world population becoming either overweight or obese.2 Most governments have acknowledged the obesity pandemic as a major concern because of its complex physiological, social, and economic effects. Despite the wealth of knowledge of the multiple physical, psychological, and economic dangers associated with increased body weight and obesity, as a society we still struggle to understand the etiology and appropriate treatment for it.
A novel line of research approaches the obesity epidemic from the standpoint of addiction. The brain mechanisms underlying the drive to procure and consume food are the same as those that are “hijacked” when one becomes dependent on a drug. It may be that some obese individuals may have an unhealthy preoccupation with food, which could result in behavioral and brain changes that make the individual unable to control their food intake, resulting in irrational and unhealthy eating patterns. Scientists only recently have begun to assess this concept in controlled laboratory studies.3,4
Preclinical studies using rodent models have investigated the behavioral and physiological changes that occur when rats are given intermittent access to palatable foods. Rats with limited access to sucrose (table sugar) binge on it upon access and show signs of tolerance, evidenced by increasing their daily intake and binge (first hour) intake of the sugar.3 Compared with control groups, rats with intermittent sucrose access also show signs of opiate-like withdrawal (eg, anxiety, tremor) when deprived of sucrose for more than 24 hours, or when they are injected with an opioid antagonist.5,6 Rats also show decreased body temperature and aggression, both of which are seen during drug withdrawal.7,8 Intermittent sucrosefed rats also show signs of craving and increased responding for sugar-associated cues.7,8
Palatable Foods’ Effects on the Brain
Complementary findings have been observed with other palatable foods.9 Rats that overeat pure fat will also binge on it, as well as on sugar-fat combinations, such as Oreo cookies.10 Rats with binge access to fat have a higher progressive-ratio breakpoint than non-bingeing rats, which suggests a greater willingness to work for a fat reinforcer. Also, rats with binge access to sweet-fat combinations will cross a shock grid to obtain them. These data suggest several behavioral overlaps between overeating of palatable food and drug addiction (Table, see page 480).
Table. Symptomatology of Palatable Food Addiction and Empirical Studies Evidence
There are also notable overlaps between neurochemical pathways activated by the overeating of palatable foods and by drugs of abuse.15 Studies suggest that overeating sugar or sugar-rich food produces a neural state in which mesolimbic dopamine (DA) receptors and gene expression are altered and resemble those seen in an animal dependent on a drug of abuse.3,16
Further, administration of most drugs of abuse results in increased levels of extracellular DA in the nucleus accumbens (NAc); this DA release is integral to the reinforcement value of abused substances. While food can also release accumbens DA, under normal circumstances, this DA release wanes with repeated access once the palatable food is no longer novel.17 However, when rats overeat sugar, they repeatedly release accumbens DA (Figure, see page 480);16 this response is more similar to that of a drug than a food. Besides these changes, overeating palatable sugar- or fat-rich foods affects opioid receptor binding and gene expression in the NAc region, again in ways similar to the effects of drugs of abuse.11,19,20
Figure. Animals fed binge access to sugar maintain increased levels of extracellular DA following sugar binges. DA levels increased for the rats bingeing on sugar each day (open circles) on days 1 and 2, and again on day 21 of access. DA levels increased significantly for the rats offered sugar twice (filled circles), ad libitum sugar, and binge chow (open squares) control groups on day 1, but there was a blunting of this effect by day 21. The ordinate indicates the hour (0 to 60 minutes) of sugar and chow availability for this test. * P<.05. Source: Adapted with permission from: Rada P, Avena NM, Hoebel BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience. 2005;134(3):737–744.
Clinical studies have extended the anecdotal accounts of food addiction. The Yale Food Addiction Scale, a psychometric scale to measure food addiction in humans, has been developed by adapting the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), criteria used to classify patients as being substance-dependent.4 Neuroimaging data reveal that, in response to the anticipation of food, scores on the Yale Food Addiction Scale correlate with activation of brain regions seen in response to drugs of abuse, such as the anterior cingulate cortex, medial orbitofrontal cortex, and amygdala.21 As additional overlaps are noted between food and drug addictions, we also may begin to see overlaps in their treatment approaches.22
Food Addiction and Sensitization to Drugs
Cross-sensitization to drugs of abuse is well-documented in the literature. When an individual is dependent on one drug, he can have a heightened response to another, similar drug. In animal models, cross-sensitization has been demonstrated with several drugs.23,24 Studies have reported cross-sensitization between drugs and other non-drug events, such as stress,25 sexual behaviors,26 and even the consumption of palatable food.27 Studies of humans also show cross-sensitization among drugs,28 contributing to poly-drug abuse.
Enhanced mesolimbic dopaminergic or opioid neurotransmission may play a major role in the behavioral effects of drug sensitization, as well as cross-sensitization, and may be a contributing factor in drug addiction. Repeated exposure to DA agonists such as amphetamines can produce a state of intermittent DA release after a period of low basal DA transmission; this intermittent activation of the mesolimbic DA system in the context of low DA transmission may facilitate drug sensitization.12,13,28
Evidence suggests that overconsumption of food can produce a state conducive to cross-sensitization. For example, rats maintained on a diet of binge-access amounts of sugar for a month, followed by 8 days of no sugar access, were then given a low dose of amphetamine.12 Rats with a history of overeating sugar were hyperactive in response to the amphetamine. In contrast, rats with unlimited sugar access, or control groups with limited or unlimited access to chow only, did not show hyperactivity.
Similarly, rats maintained on a limited access schedule of sugar showed locomotor hyperactivity in response to a low dose of cocaine.13 In another study, rats with a history of intermittent sugar access showed a proclivity to consume alcohol.14 These findings suggest that rats with a history of signs of addiction to food are also prone to the locomotor stimulating effects of drugs, and that they also may be prone to ingest drugs when offered.
Recovering Food Addicts and Drug Sensitivity
Clinical literature supports the association of aberrant feeding behavior with drug abuse. There is comorbidity between eating disorders, such as bulimia nervosa, and substance abuse.29 In normal populations, cessation of drug intake has been associated with hyperphagia.30 For example, while cigarette smoking normally decreases appetite and food intake, which in turn can result in weight loss, smoking cessation causes hyperphagia and weight gain.31
Conversely, if food addiction is a measurable phenomenon, it is important to consider that withdrawal of palatable food may produce a state in which individuals are susceptible to becoming dependent on other substances of abuse or process addictions, such as gambling. If overeating becomes a reinforcer, then there is the danger that when food is no longer overconsumed because of weight-loss efforts, other pleasurable activities may be substituted to alleviate withdrawal associated with the loss of food abuse.
Many morbidly obese patients who have gastric bypass surgery may meet clinical criteria for a pathological attachment to palatable food, which in some can manifest as an “addiction” to food.32 Because of the abrupt changes in eating behavior that follow these surgeries, patients may begin to derive pleasure from other reinforcers, such as alcohol or drugs of abuse. Postsurgery substance abuse may be more common in this cohort because of sensitization to the reinforcing effects of the various substances. This has been suggested in other post-bariatric surgery patient studies that point to other co-addictions (eg, narcotics), as well as compulsive behaviors, such as shopping and gambling.33 Postsurgery addictions have been found to be positively associated with weight regain.34 Thus, bariatric surgeons should consider sensitivity to alcohol and other drugs of abuse that may result from previously unrecognized food addiction.
The findings that palatable food overconsumption can produce a state resembling addiction has important implications for treating some cases of obesity. This idea is supported by literature showing that obese patients have low striatal DA levels,35 as well as a greater striatal response to the presentation of palatable foods.36 This may put some individuals at a greater risk for substance abuse. This is supported by the greater familial likelihood of having alcohol-use disorders among obese patients.37 The reality that food addiction may transfer to an addiction to an illicit drug or other maladaptive behavior (gambling, shopping) should be considered.
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- Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32(1):20–39. doi:10.1016/j.neubiorev.2007.04.019 [CrossRef]
- Gearhardt AN, Corbin WR, Brownell KD. Preliminary validation of the Yale Food Addiction Scale. Appetite. 2009;52(2):430–436. doi:10.1016/j.appet.2008.12.003 [CrossRef]
- Colantuoni C, Rada P, McCarthy J, et al. Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obes Res. 2002;10(6):478–488. doi:10.1038/oby.2002.66 [CrossRef]
- Avena NM, Bocarsly ME, Rada P, Kim A, Hoebel BG. After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance. Physiol Behav. 2008;94(3):309–315. doi:10.1016/j.physbeh.2008.01.008 [CrossRef]
- Avena NM, Long KA, Hoebel BG. Sugar-dependent rats show enhanced responding for sugar after abstinence: evidence of a sugar deprivation effect. Physiol Behav. 2005;84(3):359–362. doi:10.1016/j.physbeh.2004.12.016 [CrossRef]
- Grimm JW, Fyall AM, Osincup DP. Incubation of sucrose craving: effects of reduced training and sucrose pre-loading. Physiol Behav. 2005;84(1):73–79. doi:10.1016/j.physbeh.2004.10.011 [CrossRef]
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- Colantuoni C, Schwenker J, McCarthy J, et al. Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport. 2001;12(16):3549–3552. doi:10.1097/00001756-200111160-00035 [CrossRef]
- Avena NM, Hoebel BG. A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine. Neuroscience. 2003;122(1):17–20. doi:10.1016/S0306-4522(03)00502-5 [CrossRef]
- Gosnell BA. Sucrose intake enhances behavioral sensitization produced by cocaine. Brain Res. 2005;1031(2):194–201. doi:10.1016/j.brainres.2004.10.037 [CrossRef]
- Avena NM, Carrillo CA, Needham L, Leibowitz SF, Hoebel BG. Sugar-dependent rats show enhanced intake of unsweetened ethanol. Alcohol. 2004;34(2–3):203–209. doi:10.1016/j.alcohol.2004.09.006 [CrossRef]
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- Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13(5):635–641. doi:10.1038/nn.2519 [CrossRef]
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- Rada P, Avena NM, Hoebel BG. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience. 2005;134(3):737–744. doi:10.1016/j.neuroscience.2005.04.043 [CrossRef]
- Spangler R, Wittkowski KM, Goddard NL, Avena NM, Hoebel BG, Leibowitz SF. Opiate-like effects of sugar on gene expression in reward areas of the rat brain. Brain Res Mol Brain Res. 2004;124(2):134–142. doi:10.1016/j.molbrainres.2004.02.013 [CrossRef]
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Symptomatology of Palatable Food Addiction and Empirical Studies Evidence
|Signs of Substance Dependence||Preclinical Findings|
Escalation of daily palatable food intake.10,11
Signs of withdrawal.
Somatic signs (teeth-chattering, tremor).
Anxiety measured by plus-maze.
Ultrasonic distress vocalizations.
Consuming more than intended, despite negative consequences.
Increased response for food-related cues.
Enduring footshock to get palatable food.7–9
Addiction to amphetamine, cocaine, alcohol.12–14