Animal Models Lead the Way to Further Understanding Food Addiction as Well as Providing Evidence that Drugs Used Successfully in Addictions Can Be Successful in Treating Overeating

To the Editor: We read with great interest the papers relating food and addiction in Biological Psychiatry, Volume 73, Number 9. We agree with the Commentary written by Gearhardt & Brownell (pp. 802-3) that the food addiction model can be a game changer and have summarized this evidence previously(1, 2). Reviews of the neurobiology by Smith and Robbins emphasizing opioid systems in drug and food addiction (pp. 804-10) and Newman et al. suggesting the importance of Gamma Aminobutyric Acid (pp 843-50), along with Volkow & colleagues suggesting that neurobiological advances can help us develop new prevention and treatment for overeating based on addiction models (pp. 811-18) resonate with us. One of us had reported naltrexone effects in binge eating in humans in the 1980s (3). Binge eating affects reward-related brain regions, and pharmaceutical treatments for drug addiction can also be effective in treating overeating(4). The GABA-B agonist baclofen can reduce intake of dietary fat, and the opioid antagonist naltrexone can suppress intake of some foods. The study we reported at ACNP (5) tested the effects of naltrexone-baclofen combinations on binge intake of diets consisting of palatable nutrients. Male Sprague-Dawley rats were given binge access to standard chow and a sugar solution, fat emulsion, or sugar-fat emulsion for 21 days. Rats were then administered (i.p.) naltrexone (0.1 or 1.0 mg/kg), baclofen (1.0 or 1.8 mg/kg) and naltrexone-baclofen (0.1 mg/kg naltrexone and 1.0 mg/kg baclofen, or 1.0 mg/kg naltrexone and 1.8 mg/kg baclofen) and food intake was monitored. Naltrexone-baclofen (1.0 and 1.8 mg/kg, respectively) significantly suppressed binge eating of sugar-fat emulsion. This combination was also superior to either drug alone at reducing binge consumption of the fat emulsion or sugar solution. Baclofen (1.8 mg/kg) significantly reduced binge eating of the fat and sugar-fat emulsions, but naltrexone (1.0 mg/kg) did not show a significant effect on binge consumption in either of these groups. These findings suggest that the combination of baclofen and naltrexone is superior to either drug alone in suppressing binge intake of palatable foods rich in fat and/or sugar. This drug combination may be useful as a therapeutic tool for patients who binge eat, and it also provides a novel pharmacological support for the food addiction hypothesis as both of these medications are used in alcohol dependence and other addictions. Research led by Bart Hoebel, which has been continued by his junior colleague Nicole Avena since his death, has used animal models to show that rats will readily self-administer sugar in ways that resemble drugs of abuse, with loss of control, cross tolerance, failed attempts to quit, and withdrawal signs and symptoms produced spontaneously by opiate antagonist administration(6). This laboratory model might yield new treatments as Volkow has suggested, and it provides a unique way to assess the effects of the act of overeating of palatable foods, like sugars, independent of obesity. Successful treatments for hedonic overeating would not only provide support for the food addiction hypothesis, but also suggest a common mechanism through which addictive behaviors may occur.