Naltrexone and Bupropion (Contrave)

Taking Wellbutrin and naltrexone separately is off-label and barely studied

Contrave is one tablet with fixed amounts of two drugs. Generic naltrexone and generic bupropion are sold as separate products in other strengths, for other uses.^1-3

A single 50 mg naltrexone tablet holds more naltrexone than Contrave's full daily amount of 32 mg, and Contrave splits its dose into extended-release tablets taken twice a day. Two separate prescriptions don't reproduce those doses.^1,3

The studies of separate or study-made tablets are small and short:

A methamphetamine trial (ADAPT-2) used the Vivitrol shot with bupropion, not Contrave or tablets.⁸ None of these compared separate tablets with Contrave. The warnings below come from the two ingredients, and the Wellbutrin XL and naltrexone labels carry their own seizure, alcohol and opioid rules.^1-3

Already on naltrexone or Wellbutrin? Don't add Contrave

Bupropion raises seizure risk, and the risk climbs with dose. In Contrave's trials, about 0.1% of people had a seizure, against none on placebo.¹ Two bupropion products at once add up to a higher bupropion dose. If two clinicians prescribe these drugs, make sure each knows about the other's prescription. The full list of naltrexone brand names and forms shows which products contain naltrexone.

Alcohol and Contrave: keep it low, and don't stop heavy drinking abruptly

Contrave must not be used by people who "drink a lot of alcohol and abruptly stop drinking." The same applies to stopping benzodiazepines, barbiturates or seizure medicines suddenly. All of these raise the chance of a seizure, and so does heavy drinking itself.¹ Wellbutrin XL carries the same contraindication and the same advice to minimize or avoid alcohol.²

While on Contrave, alcohol "should be minimized or avoided." Since bupropion went on sale, people who drank while taking it have rarely reported mental or nerve-related reactions, or a lower tolerance for alcohol.¹

If you drink heavily and want to stop, plan it with a clinician before starting either drug. For drinking, naltrexone alone is one of three FDA-approved medicines, at 50 mg a day; see naltrexone for alcohol use disorder, drinking on naltrexone and, for online programs, where to get naltrexone online.^3,9

Contrave is a fixed-dose tablet approved for weight management

FDA approved Contrave on September 10, 2014.¹⁰ It is meant to be used with a lower-calorie diet and more exercise. Its trials enrolled adults with a BMI of 30 or more, or 27 or more with high blood pressure or abnormal blood fats; one trial enrolled people with type 2 diabetes.¹ The label says its effect on heart attacks, strokes and deaths has not been established.¹

The dose goes up one tablet a week¹:

Doses above 2 tablets twice a day are not recommended. The label also says not to take it with a high-fat meal, which raises blood levels of both drugs and with them the seizure risk. After 12 weeks on the full dose, anyone who has not lost at least 5% of their starting weight should stop, because further loss is unlikely.¹ The same check appears on how long naltrexone takes to work, and the naltrexone dose comparison is on naltrexone dosage.

In year-long trials, Contrave beat placebo by 2 to 4 points of body weight

All four trials lasted 56 weeks and paired the drug with diet and exercise advice.¹ The figures below are from the current label, which counts everyone randomized.

Sources: Contrave label, Table 6 and Figures 1 to 3.¹

In the published papers, COR-I and COR-BMOD counted only people with a weight check while still on the drug: −6.1% vs −1.3%, and −9.3% vs −5.1%.^11,12 COR-Diabetes reported −5.0% vs −1.8% in a modified intention-to-treat group.¹³ COR-II, which is not in the label's table, reported −6.4% vs −1.2% at 56 weeks.¹⁴

Across the four trials, 45% of the placebo group and 46% of the Contrave group withdrew before week 56, most within the first 12 weeks. Side effects made 24% of people on Contrave stop, against 12% on placebo.¹

Naltrexone alone did not beat placebo for weight in small trials

Naltrexone by itself is not approved for weight loss, so using it that way is off-label.³ Two small 8-week trials from the 1980s tested it:

• 60 people with obesity took 0, 50 or 100 mg a day. Neither dose produced significant weight loss compared with placebo. Women lost 1.7 kg in a subgroup analysis, and six people had abnormal liver tests.¹⁵
• Men with obesity who also had diet counseling took 300 mg a day. Naltrexone showed no advantage over placebo, and it was linked to liver injury at that dose.¹⁶

The naltrexone tablet label describes a placebo-controlled study in people with obesity at 300 mg a day: 19% (5 of 26) developed raised liver enzymes, against none of 24 on placebo.³ There is no labeled weight-loss dose for naltrexone alone.³ Low-dose naltrexone (LDN) is a separate off-label use; see low-dose naltrexone.

Nausea is the most common side effect, and bupropion carries a boxed warning

In the pooled trials, the most common side effects on Contrave compared with placebo were¹:

• Nausea: 32.5% vs 6.7%
• Constipation: 19.2% vs 7.2%
• Headache: 17.6% vs 10.4%
• Vomiting: 10.7% vs 2.9%
• Dizziness: 9.9% vs 3.4%
• Trouble sleeping: 9.2% vs 5.9% (more on sleep: does naltrexone make you sleepy?)

Boxed warning. Bupropion is also sold as an antidepressant. In short-term trials, antidepressants raised suicidal thoughts and behavior in children, teens and young adults. People of any age starting Contrave should be watched closely for worsening mood or suicidal thoughts, and it is not approved for children.¹

Blood pressure and pulse. Contrave can raise both, and the risk may be greater in the first 3 months. At weeks 4 and 8, average heart rate was about 2 beats a minute higher than on placebo.¹

Heart safety is unsettled. A heart-outcomes trial in 8,910 people ended early after the sponsor publicly released confidential interim results. Its authors concluded that cardiovascular safety "remains uncertain" and needs a new trial.¹⁷

Naltrexone's own side effects, including liver warnings, are on naltrexone side effects.

Opioids and Contrave don't mix

Contrave is contraindicated with long-term opioid use, including methadone or buprenorphine, and during opioid withdrawal. People need to be off all opioids for 7 to 10 days before the first dose.¹ While on it, opioid painkillers, cough medicines and diarrhea medicines may not work fully.¹ After stopping, a dose of opioids someone used to take can cause a fatal overdose; the details are in the opioid and overdose warnings.

No generic Contrave can be sold yet

FDA gave a generic version (Actavis, ANDA 208043) tentative approval on November 29, 2022. Tentative approval does not allow sales, and as of FDA's October 16, 2026 data it had not become a final approval.^10,18 The status of every naltrexone brand is in the table on naltrexone brand names.

Share your experience

Have you taken naltrexone with bupropion, or switched between them and Contrave? Tell us what happened, or read other people's naltrexone reviews.

How we checked

• Sources: current DailyMed labels for Contrave and Wellbutrin XL (November 2025) and naltrexone tablets (May 2026); Drugs@FDA and FDA's tentative-approval letter; PubMed abstracts; ADAPT-2 in full; the DEA's controlled substances list.^{1-3,8,10,18,19}
• Separate-tablet studies come from 8 PubMed and 5 ClinicalTrials.gov searches on October 17, 2026. The weight table uses the label's figures.
• Not used: three binge-eating trials whose abstracts don't say which tablets were used.