Naltrexone for weight loss: doses, uses, side effects

If you’re struggling to lose weight and looking for an alternative option, naltrexone might be worth considering. Though primarily used to treat substance use disorder, naltrexone may support weight loss, especially when combined with healthy lifestyle changes and another medication. 

In this article, we’ll cover how naltrexone works for weight loss, recommended dosages, how to take it, and common side effects. We’ll also answer frequently asked questions about its effectiveness, safety, and usage.  

Naltrexone is a medication primarily used to help treat addiction. More specifically, it is approved by the US Food and Drug Administration (FDA) to treat alcohol use disorder and opioid use disorder. It works by blocking opioid receptors in the brain, which helps reduce cravings and inhibits some of the effects of alcohol or opioids. By preventing the “reward” feeling associated with these substances, naltrexone can make it easier for people to cut down on their use.

Naltrexone tablet (formerly brand name ReVia) is typically taken once daily for treating alcohol or opioid dependence. An injectable version, aka Vivitrol, is a long-acting shot given by a healthcare professional about once a month, making it a convenient option for those who prefer to avoid a daily pill. 

Developed in the 1960s, naltrexone was approved for medical use in the US in 1984. Researchers first noticed its potential to treat alcohol dependence through studies on animals, and it quickly became a key option for managing both alcohol and opioid addiction. Over time, scientists began studying how naltrexone might help with other conditions, leading to new uses beyond addiction treatment.

While oral and injectable versions of naltrexone alone are primarily used for addiction treatment, naltrexone is also available in a fixed combination product with another medication called bupropion for weight management. Bupropion, an antidepressant that can also curb appetite, can enhance the effects of naltrexone when used together. 

The naltrexone/bupropion combination is marketed under the brand name Contrave and is FDA-approved specifically for weight loss in individuals with a:

• body mass index (BMI) of 30+ (obesity) 

• BMI of 27+ (overweight) with at least one weight-related health condition, such as high blood pressure or type 2 diabetes. 

Contrave is used alongside a reduced-calorie diet and increased exercise. By working together to reduce appetite and control cravings, naltrexone/bupropion can make weight loss easier for some patients.

It’s important to note that naltrexone isn’t FDA-approved for weight loss on its own. Most research on naltrexone for weight loss involves the drug used in tandem with bupropion.

Possibly. 

Weight loss is one of the side effects listed on the prescribing information for naltrexone. However, most scientific research suggests that naltrexone alone has limited effects on weight loss. It may reduce cravings, but studies haven’t shown a clear benefit for weight loss. Some research indicates that naltrexone can make food taste bad, which could explain why some people may eat less and experience some weight loss while taking the medication. But findings are inconsistent, and not all studies report this effect.  

In one study, 44 women with obesity took 25 mg of naltrexone, 50 mg of naltrexone, or a placebo. Researchers looked at the drug’s effects on cravings and reward-based eating habits. While the results showed no difference in craving intensity, naltrexone was better than the placebo at reducing the link between cravings and reward-based eating. However, since this study focused on behavioral aspects, it’s unclear if actual weight loss occurred.

More reliable results in terms of weight loss come from the combination of naltrexone with bupropion—and most of the research on naltrexone for weight loss looks at the combo rather than naltrexone alone.

As mentioned above, naltrexone is commonly paired with bupropion for weight management as Contrave. It’s a two-in-one oral tablet that’s FDA-approved for weight loss. According to the drug manufacturer, you may start seeing results within 12 weeks after reaching the recommended dosage of Contrave (more on this later). If you haven’t lost 5% of your body weight within this timeframe, your healthcare provider may suggest stopping the drug because it doesn’t work for everyone.

So, how much weight can people lose while taking the naltrexone/bupropion combination? Let’s look at what studies have shown.

A large review of studies found that naltrexone/bupropion led to significant weight loss, with many participants losing 5-10% of their body weight. One study in this review showed an average weight loss of around 11 pounds with naltrexone/bupropion. In four of the reviewed studies, weight loss was assessed after about 13 months, while some people saw results in as little as 6 months.

Another study looked at how well naltrexone/bupropion worked for weight loss compared to bupropion alone in 419 people with obesity over nearly six months (24 weeks, to be exact). The naltrexone/bupropion group had the most significant weight loss overall, and participants saw continued weight loss over 11 months, suggesting lasting effects. 

In another clinical trial, people taking naltrexone/bupropion lost an average of 6.1% of their body weight by about 13 months, compared to weight loss of 1.3% in those without any treatment. 

Keep in mind that real-life results can vary from those seen in studies. Much of naltrexone’s effects depend on lifestyle and personal health factors. The best outcomes with weight loss medications typically involve a multi-pronged approach, combining calorie reduction, increased physical activity, and healthy eating habits, among other strategies.

Scientists are still exploring exactly how naltrexone promotes weight loss. It’s thought to work by blocking the endorphins, or “feel-good” chemicals, that are released during pleasurable activities, such as eating a favorite treat. By reducing this reward, naltrexone may help people stay on track with a healthful diet and feel less drawn by food cravings.

In the naltrexone/bupropion combination (Contrave), the two drugs work together to activate neurons in the brain responsible for controlling appetite. Bupropion, originally known as the brand-name drug Wellbutrin, can help balance certain brain chemicals, like dopamine, that influence mood and cravings. When taken alone, it is sometimes also used in the treatment of depression or even when people are trying to quit smoking. For weight loss, bupropion may help reduce appetite and encourage the body to use more energy. The combination of these effects can make Contrave an effective option for weight loss.

Like any medication, naltrexone may come with side effects. The following common side effects were reported in more than 10% of people using naltrexone for addiction treatment in studies:

• Insomnia

• Anxiety or nervousness

• Stomach pain 

• Nausea or vomiting

• Low energy

• Pain in joints or muscles

• Headache

Similar side effects can occur when naltrexone is taken with bupropion. Common Contrave side effects may include:

• Nausea

• Constipation 

• Headache

• Vomiting

• Dizziness

• Insomnia

• Dry mouth

• Diarrhea

Taking naltrexone or Contrave with food can help minimize stomach issues and nausea. However, taking Contrave with or after a high-fat meal (such as a burger and fries) greatly increases the levels of naltrexone and bupropion in your body, which can exacerbate side effects. So, while it’s a good idea to take the medication with food, it’s typically recommended to avoid high-fat foods. 

More serious side effects can happen, but they’re rare. Some serious side effects of naltrexone alone (particularly when taken in excess) include allergic reactions, such as trouble breathing or swelling of the lips or tongue, as well as confusion, hallucinations, blurry vision, and severe diarrhea or vomiting. 

For the combination of naltrexone/bupropion, additional serious risks may include seizures, chest pain, high blood pressure, suicidal thoughts, and a rare eye condition called angle-closure glaucoma. 

If you experience any severe side effects, contact your healthcare provider immediately and seek emergency medical attention. Before starting naltrexone or Contrave, be sure to discuss your medical history, current medications, and supplements with them to help prevent unwanted side effects or interactions.

While naltrexone can be effective for some people, it’s not safe for everyone. Certain conditions and medications may increase the risk of side effects. A healthcare provider can help determine when to avoid naltrexone completely vs take it with caution.

You should avoid naltrexone if you:

• Are taking opioid painkillers or anticipate needing painkillers (think: after an operation)

• Have recently stopped using opioids

• Are experiencing opioid withdrawal

• Have had a positive urine test for opioids 

• Have failed a naloxone challenge test (used to check for opioid dependence)

Naltrexone is also not recommended if you are allergic to it or any of its ingredients.

Certain conditions also require extra caution with naltrexone, so it’s important to talk with your healthcare provider if you:

• Have liver disease

• Have kidney disease

• Are pregnant or breastfeeding

• Are under 18 (the safety of naltrexone hasn’t been studied in this age group)

The combination medication, Contrave, has additional warnings and considerations. You should avoid it if you:

• Have a history of seizures

• Have uncontrolled high blood pressure

• Have a substance use disorder

• Have a history of eating disorders, such as bulimia or anorexia nervosa

• Have taken monoamine oxidase inhibitors (MAOIs) in the last 14 days

• Use opioid pain medications

• Are in the process of discontinuing alcohol, benzodiazepines, barbiturates, and/or anti-seizure medications

• Are using other forms of bupropion 

Contrave may not be recommended if you have suicidal thoughts, heart disease, liver issues, or type 2 diabetes (due to a possible risk of low blood sugar). If you have any doubts, speak to a healthcare provider.

Most studies of naltrexone for weight loss use the naltrexone/bupropion combination, Contrave. It comes as an extended-release oral tablet that contains 8 mg of naltrexone and 90 mg of bupropion. You may see the dose written as “8 mg/90 mg.” The usual starting dosage is one tablet daily, with a gradual increase each week until you reach the target dosage of two tablets taken twice daily. The table below shows the typical starting dosage schedule for Contrave.

For weight loss, naltrexone is often prescribed off-label as an oral tablet, available in one strength of 50 mg. 

For naltrexone alone, the dosing is often tailored based on what it’s being used to treat. For example, naltrexone doses for treating alcohol use disorder range from 50 mg daily to 100 mg daily. Since naltrexone isn’t approved by itself for weight loss, there’s no official dosage for this purpose and no “best” dose of naltrexone for weight loss. 

There’s also no best time of day to take naltrexone. But consider taking it around the same time daily to help make it part of your routine. If you take Contrave, you’ll likely take it once in the morning and once in the evening. Be sure to follow your prescriber’s directions.

Both naltrexone and Contrave can be taken with or without food, but taking the medications with food can help prevent nausea and stomach discomfort. As explained above, avoid taking the medications alongside high-fat food as it can increase the side effects. Swallow each tablet whole with water, and avoid cutting, crushing, or chewing them, as this can alter how the medication is absorbed.

Curious about whether it’s okay to drink alcohol while taking naltrexone/bupropion? Alcohol can make side effects, like nausea and high blood pressure, worse when combined with these medications. Check with your healthcare provider to see if they recommend limiting or avoiding alcohol. 

When comparing naltrexone to Contrave, we’ve already covered several similarities and differences. Here’s a recap of the key differences:

• Naltrexone contains one ingredient that may play a role in reducing cravings. But research shows minimal weight loss effects with naltrexone alone. 

• Most studies demonstrate that the combination of two active ingredients—naltrexone and bupropion—offers more substantial weight loss results than either drug alone. The combination is available as the brand-name drug Contrave. 

• Contrave is FDA-approved for weight management. Studies show that many people lose at least 5% of their body weight while taking the drug.

Naltrexone is available as a generic, which makes it more affordable. Contrave, however, is only available as a brand medication and tends to be more expensive. A one-month supply of Contrave at major pharmacies generally costs between $650 and $660 without insurance, whereas generic naltrexone is much less, around $35 to $45. These estimates are from SingleCare and may vary based on factors such as location and preferred pharmacy.

You might be able to cut costs by signing up for Contrave’s savings offering, the CurAccess Program, which offers the medication for $99 or less (eligibility restrictions apply).

As is the case with all prescription medications—and treatments in general, for that matter—naltrexone/buproprion may not be right for everyone. The good news? There are several other weight loss medications available that may be worth considering and discussing with your healthcare provider. Here’s a brief overview of some common alternatives that are FDA-approved for weight loss in certain people, along with some pros and cons to consider for each one.

Phentermine

Phentermine is an appetite suppressant and is typically prescribed for short-term use, generally for a few weeks to a few months.

• Pros: Phentermine can be effective for short-term weight loss and can be particularly helpful for jumpstarting weight loss efforts. It’s generally affordable, especially in generic form.

• Cons: Phentermine is a stimulant and can cause side effects such as increased heart rate, insomnia, and anxiety. It’s also not recommended for long-term use due to the risk of misuse, dependence, and cardiovascular side effects.

Qsymia

Qsymia is a combination of phentermine and topiramate that can help reduce appetite and increase feelings of fullness. It is FDA-approved for long-term weight management and is usually more effective than phentermine alone.

• Pros: Qsymia can provide more sustained weight loss than phentermine alone. It’s also approved for longer-term use.

• Cons: Qsymia can cause side effects such as dry mouth, constipation, and a tingling sensation in the hands or feet. It isn’t currently available as a generic.

Xenical 

Xenical (orlistat) is a prescription medication that works by blocking the absorption of fat in the digestive system. It’s also available over-the-counter (OTC) in a lower dose as Alli.

• Pros: Xenical is a non-stimulant option and can be used for long-term weight loss. It may also support improved cholesterol levels by reducing fat absorption.

• Cons: The side effects of Xenical are primarily gastrointestinal, including gas, oily stools, and frequent bowel movements, which can be uncomfortable. Additionally, it may not be effective unless paired with a reduced-fat diet.

Wegovy 

Wegovy contains the active ingredient semaglutide, a medication originally developed to manage type 2 diabetes. As a GLP-1 agonist, it works by mimicking a hormone that helps control appetite and blood sugar. Semaglutide is also found in Ozempic, Rybelsus, and compounded medications.

• Pros: Wegovy has been proven highly effective for weight loss and long-term weight maintenance, with clinical trials demonstrating 9.6–16% weight loss after 68 weeks of treatment. The drug can also reduce cardiovascular risks in people with heart disease and obesity or overweight.

• Cons: Common side effects include nausea, vomiting, and diarrhea. Additionally, it can be quite expensive and not covered by all insurance plans. 

Saxenda 

Saxenda (liraglutide) is another injectable medication used for weight loss, and it also works by mimicking a hormone that controls appetite. Like Wegovy, Saxenda was initially developed for managing diabetes.

• Pros: Saxenda can effectively support long-term weight loss and is generally well-tolerated. Clinical trial results for Saxenda show weight loss of 4.9–7.4% after 56 weeks of treatment.

• Cons: Saxenda must be injected daily, which can be inconvenient. Side effects are similar to Wegovy and include nausea, vomiting, and potential gastrointestinal discomfort. It can also be expensive and may not be covered by insurance.

Zepbound 

Zepbound (tirzepatide) is a newer medication that can help you feel full longer. It mimics the effects of two appetite-regulating hormones, GLP-1 and GIP, making it unique compared to similar injectable weight loss medications. 

• Pros: Zepbound is highly effective for weight loss, with studies showing weight loss of 12.8–20.9% after 72 weeks of treatment. It’s injected once a week.

• Cons: As a newer drug, Zepbound can be expensive, and insurance may not cover it. Common side effects include gastrointestinal issues such as nausea and diarrhea.

When naltrexone is combined with bupropion (Contrave), it can help some people lose weight. By itself, naltrexone isn’t a top choice recommendation for weight management. Schedule an appointment with a healthcare provider to see if Contrave or another weight loss medication may be a good fit for you.

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About the medical reviewers

Beverly Tchang, MD

Beverly Tchang, MD, is an Obesity Medicine Advisor for Ro. She is also an assistant professor of Clinical Medicine at Weill Cornell Medicine in New York and triple board-certified in Internal Medicine, Endocrinology, and Obesity Medicine.

Raagini Yedidi, MD

Raagini Yedidi, MD, is an internal medicine resident and medical reviewer for Ro.