Naltrexone & Bupropion For Weight Loss Explained

Mike Bohl, MD, MPH, ALM

Reviewed by Mike Bohl, MD

Written by Lauren Panoff

Published 04/05/2024

Various supplements and drug combinations, including injections and oral meds, have recently found themselves in the spotlight as potential weight loss solutions. But two medications you might not think of when it comes to weight loss? Naltrexone and bupropion.

While it’s not the primary use for either medication, they’re sometimes prescribed together for conditions such as obesity or alcohol dependence. It turns out that this combination may have appetite-suppressing effects, contributing to weight loss. 

While research is ongoing, this combined therapy was FDA-approved for obesity treatment in 2014 and can be part of a comprehensive weight loss strategy. It has the potential to offer long-term benefits for adults with obesity when combined with other lifestyle interventions and calorie reduction. 

Let’s break down the uses, potential side effects, effectiveness and more of naltrexone and bupropion individually, as well as their efficacy together as weight loss medications.

Naltrexone is a medication primarily used to treat alcohol and opioid dependence. As an opioid receptor antagonist, it works by blocking the effects of opioids in the brain. This helps diminish the rewarding effects of these substances, reducing cravings for them.

You can also find naltrexone under the brand names ReVia®, Depade® and Vivitrol®.

Naltrexone Uses — Does it Cause Weight Loss? 

In addition to helping break addictions to alcohol and opioids, naltrexone may help reduce the association between reward-driven eating and craving intensity. Its ability to target the brain’s reward center makes it a promising tool for weight management, particularly for people who have a food addiction.

Bupropion (AKA Wellbutrin, one of its brand names) is primarily used as an antidepressant medication, to treat major depressive disorder. It works by inhibiting the reuptake of the neurotransmitters dopamine and norepinephrine in the brain, which increases their levels where neurons communicate with one another and may help improve your mood. 

Beyond its antidepressant properties, bupropion is used to support smoking cessation and as a treatment for seasonal affective disorder (SAD). It’s also used off-label — meaning it’s used for a different purpose than what the FDA has approved it for —  to treat conditions like attention-deficit/hyperactivity disorder (ADHD). And finally, it’s being used more often in weight loss regimens — generally in conjunction with naltrexone.

You might see bupropion sold under the brand names Wellbutrin, Zyban®, Aplenzin® and Forfivo XL®.

Does Bupropion Cause Weight Loss?

Bupropion can reduce cravings, which can be helpful for individuals struggling with weight gain and overeating. Research suggests it can also enhance metabolism, further supporting weight loss goals.

The combination of naltrexone and bupropion for weight loss, often sold as a medication called Contrave®, is effective as a duo because each drug has unique characteristics. Together, they target multiple pathways involved in appetite regulation and food cravings.

Naltrexone may reduce the rewarding effects of food, helping individuals control their calorie intake.

What about bupropion and weight loss? By affecting neurotransmitters like dopamine and norepinephrine, this drug may reduce appetite and food cravings. Plus, it may boost metabolism, which translates to more calories burned. 

What to Expect

It’s important to manage your expectations when starting naltrexone and bupropion for weight loss. They’re generally effective, but as with any drug, experiences can vary between individuals.  

For instance, many people experience a reduction in appetite and cravings, which can help them manage overeating habits that have been working against them. Some people may experience a mood-improving benefit (thanks to the antidepressant mechanisms of bupropion), which may translate to increased energy levels and motivation to be physically active.

But this combination isn’t a “magic bullet” — it’s just one aspect of your weight loss toolkit. It won’t result in quick or instant weight loss, but it can give you some behind-the-scenes support for gradual weight loss. 

Whether or not you experience the effects we listed above, weight loss drugs are most effective when combined with eating more lean protein, fruits, vegetables and whole grains as well as regular exercise and other healthy habits.

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Naltrexone and bupropion are generally safe. However, as with any drug, each medication has potential side effects to consider. Some of the most commonly reported side effects when these medications are used together include:

  • Nausea

  • Headache

  • Constipation

  • Dizziness

  • Insomnia

  • Dry mouth

  • Increased heart rate

  • Hypertension

  • Anxiety

  • Irritability

  • Tremors

It’s also important to note that like other antidepressants, bupropion can worsen depressive symptoms or lead to suicidal thoughts — especially in people with a history of mental health struggles. Wellbutrin has a black box warning for this.

Potential Interactions

If you decide to use naltrexone and bupropion together for weight loss, you’ll have to work closely with your doctor so they can monitor you for side effects and interactions with other medications.

Some of the most significant interaction risks with these drugs include:

  • Opioid medications: Naltrexone, as an opioid antagonist, can diminish the effects of opioid medications. Therefore, you shouldn’t use it at the same time as opioid pain medications or opioid-containing cough medications.

  • Alcohol: Combining naltrexone with alcohol can increase the risk of liver damage. Therefore, individuals using naltrexone should avoid consuming alcohol.

  • Monoamine oxidase inhibitors (MAOIs): Bupropion should not be used with MAOIs, a type of antidepressant, or within 14 days of discontinuing an MAOI. Using them together can increase your risk of a sudden spike in blood pressure called a hypertensive crisis.

  • Other medications that lower the seizure threshold: Bupropion can lower the seizure threshold.

  • CYP2B6 inducers and inhibitors: Bupropion is metabolized by an enzyme called CYP2B6. Drugs that target this enzyme may affect the metabolism of bupropion, leading to changes in its efficacy or toxicity.

  • Drugs that raise blood pressure: Bupropion may increase blood pressure and heart rate. Therefore, you should use caution when combining bupropion with other medications that can raise blood pressure.

Who Shouldn’t Use Naltrexone and Bupropion?

Not every medication is suitable for every person. It’s essential to talk to your doctor before using naltrexone and bupropion (individually or together as Contrave) if you: 

  • Have an allergy or hypersensitivity: Practice common sense. You shouldn’t take naltrexone, bupropion or Contrave if you’ve had a previous allergic reaction to these medications or any ingredients in them.

  • Have liver disease: Both naltrexone and bupropion are metabolized in the liver, so you should avoid using these medications if you have severe liver impairment due to toxicity risk.

  • Have an eating disorder: Contrave may make disordered eating patterns worse in people with a history of eating disorders like anorexia nervosa or bulimia.

  • Are pregnant or breastfeeding: The safety of naltrexone and bupropion during pregnancy and breastfeeding is not well-established, but the risks outweigh the potential benefits.

As mentioned above, naltrexone and bupropion can also pose risks for people who are taking MAOIs or seizure medications or who are taking other opioids. Therefore, people who are taking these medications, have a seizure disorder, are dependent on opioids or who are going through opioid withdrawal shouldn’t take Contrave.

Are There Alternatives?

Okay, so what if naltrexone and bupropion aren’t good options for you? If you still want to take weight loss medication, other prescription medications approved for weight loss may be suitable alternatives. For example, orlistat, which works by inhibiting the absorption of dietary fat, and liraglutide, which acts on hormones in the gut to reduce appetite, may be better options.

If you have severe obesity and are seeking non-medication approaches, you may also consider surgical procedures like gastric bypass surgery, gastric sleeve surgery or gastric balloon placement. 

Talk to your healthcare provider to find the best alternatives for your needs.

If your doctor prescribes a combination of naltrexone and bupropion for weight loss, a complex dose titration approach is required. This means the dose has to be adjusted over time to achieve the maximum benefit without adverse effects.

The typical starting dose is one tablet (8 mg naltrexone/90 mg bupropion) once daily for the first week. Then your dose will be gradually increased to the recommended maintenance dose of two tablets twice daily (totaling 32 mg naltrexone/360 mg bupropion per day) by the end of week four.

Most importantly, always use naltrexone and bupropion as directed by your healthcare provider. Tell them if you have any questions or concerns, and only make any changes after getting medical advice. 

How to Improve Effectiveness 

When it comes to weight loss, you should never put all your eggs in one basket. In other words, rather than relying on naltrexone and bupropion alone to reach your weight loss goals, it’s important to consider them as just one part of a comprehensive lifestyle approach. 

Other things that can help you reach and maintain your weight loss goals include:

  • A healthy diet: While weight loss requires a calorie deficit, it’s just as important to make sure you eat nutrient-dense foods that provide a mix of lean protein, unsaturated fats, fiber and antioxidants. Incorporate foods like fruits, vegetables, whole grains, legumes, nuts and seeds into your diet to support overall wellness and healthy weight loss.

  • Exercise: Regular physical activity is critical for achieving and maintaining weight goals. Aim to exercise for at least 175 minutes per week — which could be 30 minutes most days — and try to include a variety of activities. 

  • Stress management: Reducing stress is an important aspect of successful weight loss. Whether your thing is meditation, nature walks, journaling or making balloon animals, consider ways to alleviate your stress levels.

  • Social support: Positive social support and encouragement benefit obesity treatment. You can join a community support program or share with a friend embarking on a similar journey.

  • Improved sleep: Not sleeping well makes us crabby. Research also shows that lack of sleep messes with key hormones that regulate appetite and weight, making it harder to achieve your goals.

  • Behavioral therapy: Most of us face mental health challenges at some point, and behavioral therapy has been shown to be an effective piece of obesity support. After all, weight challenges often have a deeper psychological aspect.

The combination of bupropion and naltrexone for weight loss, sold as Contrave, isn’t for everyone, but it can be an effective tool, especially when combined with other lifestyle habits. 

Here are some key takeaways if you’re considering this approach: 

  • Make it multi-faceted. To increase efficacy, use Contrave with a nutrient-dense and reduced-calorie diet, regular exercise and lifestyle habits that support weight loss, like behavioral therapy, social support and stress management. 

  • Remember there are no quick fixes. Contrave can be effective, but it isn’t a quick fix for weight loss, nor is it meant to be the only thing you do to achieve your goals. Weight loss takes time, and it’s important to do what feels right to you.

  • Work with your healthcare provider(s). Weight loss drugs like naltrexone and bupropion shouldn’t be taken lightly. Like anything else, they come with their share of potential side effects and contraindications. Work closely with your healthcare professional to ensure proper usage and safety. 

Ready to explore weight loss treatment options? Start by taking our free assessment.

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Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at [email protected]!

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Mike Bohl, MD

Dr. Mike Bohl is a licensed physician, a Medical Advisor at Hims & Hers, and the Director of Scientific & Medical Content at a stealth biotech startup, where he is involved in pharmaceutical drug development. Prior to joining Hims & Hers, Dr. Bohl spent several years working in digital health, focusing on patient education. He has also worked in medical journalism for The Dr. Oz Show (receiving recognition for contributions from the National Academy of Television Arts and Sciences when the show won Outstanding Informative Talk Show at the 2016–2017 Daytime Emmy® Awards) and at Sharecare. He is a Medical Expert Board Member at Eat This, Not That! and a Board Member at International Veterinary Outreach.

Dr. Bohl obtained his Bachelor of Arts and Doctor of Medicine from Brown University, his Master of Public Health from Columbia University, and his Master of Liberal Arts in Extension Studies—Journalism from Harvard University. He is currently pursuing a Master of Business Administration and Master of Science in Healthcare Leadership at Cornell University. Dr. Bohl trained in internal medicine with a focus on community health at NYU Langone Health.

Dr. Bohl is Certified in Public Health by the National Board of Public Health Examiners, Medical Writer Certified by the American Medical Writers Association, a certified Editor in the Life Sciences by the Board of Editors in the Life Sciences, a Certified Personal Trainer and Certified Nutrition Coach by the National Academy of Sports Medicine, and a Board Certified Medical Affairs Specialist by the Accreditation Council for Medical Affairs. He has graduate certificates in Digital Storytelling and Marketing Management & Digital Strategy from Harvard Extension School and certificates in Business Law and Corporate Governance from Cornell Law School.

In addition to his written work, Dr. Bohl has experience creating medical segments for radio and producing patient education videos. He has also spent time conducting orthopedic and biomaterial research at Case Western Reserve University and University Hospitals of Cleveland and practicing clinically as a general practitioner on international medical aid projects with Medical Ministry International.

Dr. Bohl lives in Manhattan and enjoys biking, resistance training, sailing, scuba diving, skiing, tennis, and traveling. You can find Dr. Bohl on LinkedIn for more information.

Publications

  • Younesi, M., Knapik, D. M., Cumsky, J., Donmez, B. O., He, P., Islam, A., Learn, G., McClellan, P., Bohl, M., Gillespie, R. J., & Akkus, O. (2017). Effects of PDGF-BB delivery from heparinized collagen sutures on the healing of lacerated chicken flexor tendon in vivo. Acta biomaterialia, 63, 200–209. https://www.sciencedirect.com/science/article/abs/pii/S1742706117305652?via%3Dihub

  • Gebhart, J. J., Weinberg, D. S., Bohl, M. S., & Liu, R. W. (2016). Relationship between pelvic incidence and osteoarthritis of the hip. Bone & joint research, 5(2), 66–72. https://boneandjoint.org.uk/Article/10.1302/2046-3758.52.2000552

  • Gebhart, J. J., Bohl, M. S., Weinberg, D. S., Cooperman, D. R., & Liu, R. W. (2015). Pelvic Incidence and Acetabular Version in Slipped Capital Femoral Epiphysis. Journal of pediatric orthopedics, 35(6), 565–570. https://journals.lww.com/pedorthopaedics/abstract/2015/09000/pelvic_incidence_and_acetabular_version_in_slipped.5.aspx

  • Islam, A., Bohl, M. S., Tsai, A. G., Younesi, M., Gillespie, R., & Akkus, O. (2015). Biomechanical evaluation of a novel suturing scheme for grafting load-bearing collagen scaffolds for rotator cuff repair. Clinical biomechanics (Bristol, Avon), 30(7), 669–675. https://www.clinbiomech.com/article/S0268-0033(15)00143-6/fulltext

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