A recently approved drug for weight loss called Contrave contains 8mg of the drug naltrexone combined with 90mg of bupropion (marketed on its own as Wellbutrin). Naltrexone was first approved in a dose of 50mg per day for helping opioid and alcohol addicts improve their chances of getting sober. The lower doses were proposed later by healthcare professionals who found that the drug could benefit a variety of other health problems. One of the most serious health problems in the United States today is obesity. Medically-assisted weight loss programs have grown in popularity because of this. Naltrexone has found a new application as a weight loss medication that is effective when combined with diet and exercise.
How Naltrexone Improves Weight Loss
Naltrexone was first used for preventing abuse of substances with addiction potential. Painkiller, alcohol, and tobacco addictions have all been treated with this drug. The mechanism by which it is able to manage these addictions may be the same by which it helps manage eating habits. Naltrexone is an opioid antagonist that may work by affecting the reward system and other systems to influence food intake and body weight.
In a study on naltrexone and bupropion combination, it was shown that the medication helped reduce brain activity in areas associated with food cravings. The areas of the brain that showed decreased activity are associated with saliency attribution (relative importance of food), interoception (sensation of being hungry), and craving.
In one double-blind placebo-controlled study with 20 participants, volunteers were given pasta and asked to stop eating occasionally to provide feedback on their appetite. Naltrexone reduced both the eating rate and the pleasantness of the food. When the participants were given naltrexone they ate significantly less than when given a placebo and less than when no pill was given.
Naltrexone is usually taken at night and may provide additional benefits that help with weight loss. It has been shown that for patients with chronic pain, naltrexone can improve sleep. In a study of 68,183 women over 16 years it was found that getting less than five hours of sleep each night produced a greater risk of weight gain.
Combination of Naltrexone/Bupropion
Contrave is an FDA-approved drug indicated for individuals who have a BMI over 30, which is considered obese. It may be used in those with a BMI between 27-30 who also have a weight-related comorbidity such as hypertension or diabetes. In studies it has been shown that a combination with these two drugs, when used as a part of a diet and exercise program, produces greater weight loss than a placebo with diet and exercise.
The results of patient questionnaires in multiple studies have shown that the combination of naltrexone and bupropion is effective. Patients report that they are better able to control their eating after using this combination and showed greater weight loss results at the end of the studies.
As a monotherapy, naltrexone has not yet been demonstrated to be as effective as when used in combination with bupropion. Together the drugs affect the production of pro-opiomelanocortin (POMC) – a precursor protein that affects many important biological processes. POMC is cleaved to make other proteins that have important roles in the regulation of appetite.
A drug combination with bupropion and naltrexone for weight loss should be titrated up each week for the first four weeks. In the first week the patient will take one dose each morning and none at night. This will be titrated up each week until the patient is taking two doses in the morning and two at night during week four and onwards.
Medically Supervised Weight Loss
Any weight loss plan that includes the use of a low calorie diet or weight loss medications should be supervised by a trained healthcare professional. One reason for this is that many patients that are obese have health issues related to their weight including diabetes and hypertension. It has been shown that medications for weight loss are often effective and safe for patients with obesity-related health conditions. Naltrexone has been used for many years and healthcare professionals generally feel confident prescribing it off-label due to its low toxicity. Multiple dosages of naltrexone and naltrexone combined with bupropion are available from a compounding pharmacy.
- Naltrexone/Bupropion (Contrave) for Weight Loss – American Family Physician
- Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect. – Physiology & Behavior
- Association between Reduced Sleep and Weight Gain in Women – American Journal of Epidemiology
- Pharmacotherapy for obesity in individuals with type 2 diabetes. – Expert Opinion on Pharmacotherapy
- Effect of combined naltrexone and bupropion therapy on the brain’s functional connectivity – International Journal of Obesity