The combination of bupropion and naltrexone is sold as Contrave in the United States and Mysimba in Europe. Each tablet delivers 90 mg of bupropion and 8 mg of naltrexone. Bupropion is an atypical antidepressant that works as a norepinephrine-dopamine reuptake inhibitor. Naltrexone is an opioid receptor antagonist. Approved by the FDA in 2014 and by the EMA in 2015, the combination was designed to tackle hunger and reward-driven eating through two separate brain pathways.
Tracking your medication history and any weight changes becomes much easier when you have a dedicated log. PeptPro stores your dose history, tracks weight over time with clear progress charts, and keeps everything organized for your medical appointments. See it here.
Bupropion raises dopamine and norepinephrine levels in the central nervous system. That reduces appetite and improves mood, which matters because many people eat more when they feel low. Naltrexone blocks opioid receptors, interrupting the reward cycle that certain foods trigger after eating. These two mechanisms do not compete with each other. They target physical hunger on one side and emotional or reward-based eating on the other.
Phase 3 clinical trials showed an average weight loss of 4 to 5% after 56 weeks of combined treatment with diet and exercise (Greenway FL et al., Obesity, 2023). Roughly 30 to 40% of participants achieved at least 5% body weight loss, which clinical guidelines consider a meaningful threshold. The effect is modest compared to GLP-1 agonists, but for people who cannot access incretins or have contraindications to them, this combination may fill a gap.
Candidates for this medication are adults with a BMI of 30 kg per square meter or higher, or adults with a BMI of 27 kg per square meter or higher plus at least one weight-related comorbidity such as type 2 diabetes or high blood pressure. Contraindications include a history of seizures, bipolar disorder, anorexia or bulimia, current opioid use, and active opioid withdrawal. Anyone already taking other weight-loss medications needs individual evaluation by a prescriber.
The question of combining bupropion plus naltrexone with GLP-1 agonists comes up regularly. There is no solid evidence that this combination is safe or effective. The mechanisms are different enough that overlap sounds appealing in theory, but no clinical trial has confirmed it works without risk. Anyone already on a GLP-1 should discuss any changes with their doctor before making them.
Side effects are primarily gastrointestinal: nausea, constipation, headache, vomiting, and dizziness. Bupropion can raise blood pressure and heart rate, so monitoring matters in patients with hypertension. Insomnia and dry mouth are also reported. Naltrexone may cause abdominal discomfort and, rarely, liver reactions.
The route of administration sets this apart from GLP-1 agonists. This is a pill, not an injection, and it works primarily on the central nervous system rather than on incretin pathways. The choice between them depends on medical history, comorbidities, personal preference for how to take medication, and access to treatment.
Whether you are starting a new medication or already on one, keeping a daily record of what you take, when, and how your body responds is one of the most useful habits you can build. PeptPro gives you a dose log, weight charts, and the ability to track symptoms alongside your medication. The in-app coach Pep is available around the clock if you have questions between appointments. Check it out here and keep your medical team informed with real data.
This post is for informational purposes only and does not replace medical advice. Always consult a healthcare professional before starting, stopping, or combining any medication.