Effects of long-term therapy with naltrexone on body weight in obesity

Abstract

The endogenous opiate system is thought to be associated with the regulation of food intake and body weight. Opiate antagonists decrease food intake in animals, but there are no controlled studies in obese man to evaluate body weight response to naltrexone. Sixty obese people were randomized into three groups and given 0, 50, or 100 mg of the opiate antagonist naltrexone for 8 weeks in an outpatient, double-blind study. Weight loss was not significant in either the 50 or 100 mg groups as compared with placebo. However, when broken down by sex, women had a significant (P less than 0.05) weight loss of 1.7 kg, while men did not lose weight. Side effects were modest, but six subjects had one or more abnormal liver function test results; in one subject these abnormalities appeared to be clinically significant. The effects of naltrexone on weight loss were less than expected in light of prior animal studies, but further studies with a wider dose range of naltrexone may be indicated.

Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

“…Interestingly, the inhibitory effects of opioid receptor antagonists on food intake and body weight appear most pronounced in obese animals or when animals are fed a highly palatable diet (12,19). Similar inhibitory effects on appetite are observed clinically in humans treated with the opioid receptor antagonist naloxone, naltrexone, or nalmefene; however, body weight does not appear to be consistently affected by these treatments (3,18,26).…”

“…Subjective ratings of reward-related aspects of food palatability appear to be most related to the inhibitory effects of opioid antagonists on appetite in humans (46). Unfortunately, chronic treatment with opioid antagonists failed to produce consistent reductions in body weight clinically (3,18,26). The reason for the disparity between the acute effects of opioid receptor antagonists and chronic effects is unknown.…”

Regulation of Ingestive Behaviors in the Rat by GSK1521498, a Novel μ-Opioid Receptor-Selective Inverse Agonist

“…Clinical experience with neutral opioid receptor antagonists, such as naltrexone, demonstrates that although suppression of short-term food intake is observed (Drewnowski, 1997), a significant impact on body weight is not (Atkinson et al, 1985;Malcolm et al, 1985). It has been suggested that opioid receptor inverse agonists may be more effective than neutral antagonists in the treatment of obesity.…”

Aspectos fisiológicos do balanço energético

“…Naltrexone, um antagonista opióide de longa ação, foi utilizado em ensaios clínicos, com resultados frustrantes em baixa dose. O uso de doses mais elevadas associou-se a toxicidade hepática (138).…”