Naltrexone is an opiate antagonist. Bupropion is a noradrenergic/dopaminergic antidepressant. Bupropion and naltrexone work together in the hypothalamus to reduce cravings and hunger. They activate POMC neurons in the hypothalamus, a brain region that produces a neurotransmitter that decreases the desire to eat. In the mesolimbic area of the brain, a reward center in the brain that is stimulated by pleasurable activities such as eating, bupropion, and naltrexone can regulate these feelings of pleasure, reducing cravings to eat.
In three studies that enrolled over 4000 participants who were overweight or obese and who also had high lipid levels or high blood pressure, in all studies participants taking naltrexone and bupropion combined with a diet and exercise program lost more weight than those who were taking a placebo with the diet and exercise program. The most common side effects were nausea, constipation, and headache.