Effect of combined naltrexone and bupropion therapy on the brain’s reactivity to food cues

• Published in: International Journal of Obesity Vol. 38; no. 5; pp. 682 - 688
• Main Authors: Wang, G-J, Tomasi, D, Volkow, N D, Wang, R, Telang, F, Caparelli, E C, Dunayevich, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2014; Nature Publishing Group
• Subjects: 631/378/1488; 692/699/2743/393; 692/700/565/1436/1437; Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Alcoholism; Appetite; Appetite - drug effects; Biological and medical sciences; Brain; Bupropion; Bupropion - administration & dosage; Cues; Diet; Dopamine Uptake Inhibitors - administration & dosage; Dosage and administration; Drug abuse; Drug addiction; Drug therapy; Drug Therapy, Combination; Epidemiology; Female; Food; Ghrelin; Health Promotion and Disease Prevention; Humans; Hypothalamus; Hypothalamus - drug effects; Internal Medicine; Leptin; Magnetic Resonance Imaging; Meals - psychology; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Naltrexone; Naltrexone - administration & dosage; Narcotics; Neurobiology; Obesity; Obesity - drug therapy; Obesity - prevention & control; Original; original-article; Peptide YY; Physiological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Public Health; Smoking cessation; Substance abuse treatment; Treatment Outcome; Weight control; Weight Loss; Weight reducing preparations; Womens health; United States > US; fMRI; bupropion; naltrexone; Morphinan derivatives; Narcotic antagonist; Brain; Obesity; Drug addiction; Poison withdrawal; Nutrition; Psychotropic; Central nervous system; Nutrition disorder; Metabolic diseases; Naltrexone; Encephalon; Bupropion; Reactivity; Combined treatment; Nutritional status; Food
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2013.145

Objective: The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment. Methods: Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment. Results: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues ( P <0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P <0.05). Conclusions: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.