Naltrexone: Weight Loss Side Effects and Off-Label Uses

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Naltrexone is famously known as a harm-reduction agent, and it’s getting more popular. From 2015 to 2018, its use in alcohol use disorder (AUD) treatment in the US tripled!

But some people also tie it to weight loss.

Does that mean that patients need to avoid using the drug in their recovery journeys for fear of the side effects? Should people consider using it specifically to shed excess weight?

To answer both questions, this guide will examine naltrexone’s weight loss off-label use and side effects in-depth.

Overview of Naltrexone’s Main Use in Addiction Treatment

Before we get to the weight reduction aspect, we need to cover some basics about naltrexone. If you’re already familiar with the drug’s use in treating substance use disorders (SUDs), feel free to skip this section.

In 1963, only a couple of years after naloxone was developed, Endo Laboratories synthesized naltrexone. Both are classified as Mu opioid receptor (MOR) antagonists. However, naloxone has a much shorter half-life at 3 hours, while oral naltrexone’s half-life is around 13 hours.

At the time, the long-acting methadone was the obvious choice for treating opioid addiction. Still, as an agonist (rather than a blocker), it had some euphoric side effects and a relatively high abuse potential.

That’s why naltrexone, a pharmaceutical agent that’s both a MOR blocker and a long-acting agent, quickly became appealing to medical professionals in the SUD treatment field.

Today, naltrexone is one of the top drugs used for alcohol dependence and opioid addiction in medically assisted treatment (MAT) programs.

That’s the FDA-approved use for the drug, and you’ll find it in the form of pills or injections sold under brand names like Revia and Vivitrol. Yet, over time, people started noticing a potential off-label use based on the side effects.

Naltrexone and Weight Loss Side Effects Explained

If you take a look at the side effects listed for Revia or Vivitrol, you’ll likely notice that loss of appetite is included there.

In fact, clinical studies showed that 14% of individuals using Vivitrol 380 mg intramuscular injections experienced appetite reduction. Meanwhile, only 3% in the placebo group had the same side effect.

Now, we can look at this side effect from two perspectives:

1. MAT patients who need to use naltrexone but don’t want to lose weight.
2. Individuals who don’t suffer from SUDs but want to lose weight.

For the first group, the solution is as simple as consulting the care team. This way, they can find a diet and lifestyle that keeps patients at a healthy weight while they recover from their addiction to opioids.

But let’s focus on the second group. Is it a good idea for obese patients to use naltrexone for weight reduction?

To answer this question, we need to examine how naltrexone (a MOR antagonist) can affect appetite and what adverse effects might come with this off-label use.

Possible Mechanisms of Action

Those who believe that naltrexone helps with weight loss goals often cite its blockage of anticipatory reward.

Think of it this way: naltrexone can curb alcohol cravings by reducing the “incentive” to drink. Similarly, some people hypothesize that the drug can help patients avoid no-hunger eating habits (like emotional eating).

Additionally, naltrexone blocks the feedback autoinhibition of the hypothalamic pro-opiomelanocortin (POMC). Without digging deep into the scientific jargon, the drug increases the activity of POMC cells, which then can suppress appetite.

Problems With Using Naltrexone for Long-Term Weight Loss

Just because a couple of hypotheses show how naltrexone might reduce cravings, food intake, and appetite doesn’t mean it’s an ideal weight-loss medication.

1. The Use Isn’t FDA-Approved

The number one concern here is that naltrexone isn’t FDA-approved for weight reduction.

Remember that manufacturing companies need to do research and provide clinical data that proves that the drug is safe and effective for its intended use. Until this happens, the weight loss is just an unapproved, off-label use.

2. The Findings Aren’t Conclusive

One study shows that naltrexone could reduce reward-driven eating but isn’t good for reducing craving intensity. In fact, the study revealed that the intensity was the same for both the naltrexone and placebo groups.

Plus, in a controlled clinical trial, the group that took the drug lost an average of 3.96 lbs, while the placebo group lost around 3.3 lbs. That’s not significant enough to warrant the use of naltrexone for obese patients who don’t suffer from alcohol dependence or opioid use disorders!

Another clinical trial of sixty obese adults found that the weight-related effects of naltrexone are particularly insignificant among male patients.

3. The Side Effect Can Go Both Ways

Even if you go by the side effects noticed in SUD patients using the opioid antagonist, the evidence isn’t solid enough. Weight gain is also a possible adverse effect of drugs like Revia and Vivitrol.

So, yes, individuals could lose or gain weight while taking the drug, and there’s no way to say for sure which is going to happen.

All in all, it doesn’t seem like long-term use of naltrexone alone is good for meaningful weight loss.

Combining Naltrexone and Bupropion for Weight Loss

Although naltrexone monotherapy isn’t effective or FDA-approved for weight loss, combining it with bupropion (an antidepressant) seems promising.

In the US, you’ll find this combination medication available as extended-release tablets sold under the brand name Contrave.

Each Contrave tablet contains 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride.

How It Works

The exact mechanism behind Contrave isn’t fully understood, but there are a few hypotheses to consider.

It supposedly targets the hypothalamus and the mesolimbic dopamine reward circuit to suppress hunger and control cravings.

For reference, bupropion is a dopamine/norepinephrine reuptake inhibitor, albeit a relatively weak one. However, it’s also chemically related to amphetamines, famously known for their appetite-suppressing action.

So, you could assume that’s where the effects of bupropion on weight come from.

Its Effectiveness (Studies and Statistics)

Several studies have shown that the naltrexone/bupropion combination is more effective than using either drug alone—so much so that some experts say that naltrexone without bupropion doesn’t even have any weight loss benefits.

A systematic review of 14 articles reported that the combination is both promising and well-tolerated.

How promising? In a 56-week randomized controlled trial, subjects who only took a placebo and underwent an intensive behavior modification program (physical activity, diet changes, etc.) lost an average of 5.1% of their initial weight.

Meanwhile, using 32 mg of naltrexone with 360 mg of bupropion per day (NB32) with the behavioral modification increased the estimate to 9.3%.

Overall, 66.4% of the NB32-treated subjects lost at least 5% of the initial weight, and 29.1% lost 15% or more of their weight.

Potential Side Effects

Despite the apparent effectiveness, there are a few drawbacks. The most common side effects of using Contrave are:

• Nausea and vomiting
• Constipation/diarrhea
• Sleeping problems
• Dizziness and headache
• Dry mouth

Nausea, in particular, seems to be such a popular issue. In one study, 7% of the participants discontinued the medication because of nausea. On the other hand, only 1.2% left due to insomnia.

In the 56-week trial we cited earlier, 34.1% of the NB-treated subjects reported feeling nauseated at least once, and 4.6% discontinued the randomized study because of it.

We’ll check out some tips that can help control the adverse events a bit, but you can always consult your healthcare provider for more details.

Note that this list of effects isn’t conclusive, either.

Other side effects include tinnitus, allergic reactions, and abdominal pain. Plus, the drug could also cause suicidal thoughts, neuropsychiatric adverse effects, and increased seizure risk.

That’s why it should only be taken with care and adequate monitoring. It’s considered a prescription weight-loss medication, after all.

Who It’s Ideal For

Contrave might be a good fit for obese adults with a body mass index (BMI) of 30 kg/m² or higher. Overweight adults with a BMI of 27 kg/m² might also benefit from the drug if they have other diseases like high cholesterol, high blood pressure, or type 2 diabetes.

Currax Pharmaceuticals, the company behind Contrave, has an online assessment tool that can help you figure out your BMI. Generally speaking, if your BMI is under 27, you don’t meet the criteria for using the drug.

Who Should Avoid It

Aside from the BMI, there are some conditions and risk factors that would make Contrave a bad fit.

Here are some situations where you shouldn’t use the naltrexone/bupropion combination for treatment of obesity:

• Your blood pressure level is uncontrollably high.
• You have a history of seizures.
• You have a history of eating disorders like anorexia or bulimia.
• You’ve used an antidepressant from the monoamine oxidase inhibitors class within the last 14 days.
• You’re in opiate withdrawal or currently dependent on opioid medications (risk of overdose).
• You’re stopping alcohol, benzos, barbiturates, or antiepileptics abruptly.
• You’re taking any other medications containing bupropion.
• You’re taking any sedatives like benzos.

So, make sure to share your history with a medical professional before you start using the weight-loss drug!

Tips for Using the Naltrexone/Bupropion Combination

Healthcare professionals will provide detailed guides for how to use the medication. However, there are some general tips to consider when using Contrave.

Here are five tips that can help you control the side effects and make the most of the drug:

1. Fight the Nausea With Ginger

Since nausea is the most common adverse effect, you’ll want to prepare ahead of time.

Ginger chews and ginger tea can reduce the annoying feeling. But if they don’t cut it, ask your doctor to recommend an anti-nausea medication.

2. Drink Plenty of Water

If you’re taking Contrave, it’s also wise to stay hydrated to reduce constipation. Currax Pharmaceuticals recommends taking the tablet with 8 oz of water and drinking more water throughout the day.

Doing regular exercises might help as well.

3. Shift to a Healthy Lifestyle

Don’t rely on the drug alone. Instead, combine the medical treatment with a healthy diet and an exercise routine.

After all, some clinical studies relied on behavioral modification, not just the naltrexone/bupropion blend.

4. Don’t Eat High-Fat Meals With the Dose

No, avoiding the high-fat diet here isn’t just to aid weight loss. The fat content can actually affect the drug’s absorption rate, which could lead to a higher risk of seizures.

5. Take Your Tablets the Right Way

Your healthcare provider might tweak the dosage to suit your case, but the typical dose starts small and escalates as you progress in the treatment plan.

For instance, your doctor might start you on a single tablet daily (in the morning) for the first week. By the second week, the dosing could jump to two tables daily (one in the morning and another before dinner).

In the third week, your morning dose might increase to two tablets. A week later, you could up the dose to four tablets daily.

Either way, you should never take more than two tablets at once or a total of four tablets in a single day.

Note that if you missed a dose, you shouldn’t double the amount to compensate. Just skip this dose and get back to the schedule. Don’t forget to tell a medical professional about the mishap, too!

Other Interesting Off-Label Uses for Naltrexone

The weight-loss aspect aside, naltrexone has a few off-label uses worth mentioning.

For instance, low-dose naltrexone could be prescribed to manage chronic pain. There are also mixed results from research focused on using the drug as an adjunctive agent in treating compulsive disorders.

Final Thoughts

Naltrexone could cause either weight gain or loss and isn’t an approved treatment for weight reduction.

That said, the combination of naltrexone with the antidepressant bupropion is often more effective. So, keep that in mind if you want to discuss using medications for your weight loss journey at your next doctor’s appointment.

On the other hand, maybe you need to join a MAT program and are concerned about the effects of naltrexone therapy on your body weight. If so, get in touch with the Life Free Recovery team today to discuss the different rehab and treatment options.

FAQ

Additional Resources

• SAMHSA’s Report on the Clinical Advances in Non-agonist Therapies
• Contrave Medication Guide

CDC’s Adult BMI Calculator