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Contrave is a prescription extended-release tablet that combines two older drugs, naltrexone and bupropion. The FDA approved it on September 10, 2014, for long-term weight management in adults with obesity, or with overweight plus at least one weight-related health condition, used together with a reduced-calorie diet and more physical activity. It carries a boxed warning about suicidal thoughts and behaviors because it contains the antidepressant bupropion. In COR-I, the first of the label’s 56-week trials, average weight loss was 5.4% with Contrave and 1.3% with placebo. It is not approved for anyone under 18.
Peptide Labs does not sell Contrave or any prescription drug. This article is general information, not medical advice. Whether Contrave suits a person is a decision for a licensed prescriber.
Key Takeaways
- Contrave combines naltrexone, an opioid blocker, with bupropion, an antidepressant also used to help people quit smoking.
- It was approved in September 2014 for long-term weight management in adults; the current label was revised in November 2025.
- In the three 56-week trials reported on the label, average weight loss ranged from 3.7% to 8.1% on Contrave vs 1.7% to 4.9% on placebo, and almost half of participants dropped out.
- The most common Contrave side effects are nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea.
- It must not be used with uncontrolled high blood pressure, seizures, eating disorders, regular opioid use or MAOI antidepressants.
- The label says to stop it if a person has not lost at least 5% of body weight after 12 weeks on the full maintenance level.
What is Contrave?
What is Contrave made of? Each tablet contains naltrexone, an opioid antagonist that blocks the effects of opioid drugs, and bupropion, which acts on the brain chemicals dopamine and norepinephrine. On their own, NIDDK notes, naltrexone is used for alcohol and drug dependence, and bupropion for depression or to help people stop smoking. Contrave itself is approved only for weight management. The label says it must not be combined with other bupropion products, such as Wellbutrin or Zyban, and that combining it with other naltrexone products is not recommended.
| Contrave at a glance | Label facts (revised November 2025) |
|---|---|
| Ingredients | Naltrexone and bupropion, extended-release |
| First U.S. approval | September 10, 2014 |
| Approved use | Long-term weight management with diet and physical activity |
| Who it is for | Adults with obesity, or overweight plus a weight-related condition |
| How it is taken | Tablets by mouth in the morning and evening, increased gradually |
| Boxed warning | Suicidal thoughts and behaviors (bupropion) |
| Children | Not recommended under 18 |
| Pregnancy | Stop when pregnancy is recognized |
| Heart outcomes | Effect on heart disease and death not established |
How naltrexone bupropion works
According to the label, studies in cells and animals suggest the two drugs act on two brain areas involved in eating: the hypothalamus, which regulates appetite, and the mesolimbic dopamine circuit, part of the brain’s reward system. Together they increased the firing of appetite-regulating POMC nerve cells in lab experiments. The label adds that the exact effects leading to weight loss “are not fully understood”. NIDDK summarizes it more simply: Contrave may make people feel less hungry or full sooner. Our guide to hunger hormones explains the body signals involved.
Contrave results in the COR trials
Contrave was approved on the CONTRAVE Obesity Research (COR) program: four 56-week, placebo-controlled trials in 4,536 adults with a BMI of 30 or more, or 27 or more with high blood pressure, high cholesterol or type 2 diabetes. Participants were mostly women (83%), with an average age of 46, and everyone also received diet and exercise advice. The label reports these results:
| Trial (56 weeks) | Average weight change | Lost at least 5% | Lost at least 10% |
|---|---|---|---|
| COR-I (standard lifestyle advice) | -5.4% vs -1.3% | 42% vs 17% | 21% vs 7% |
| COR-BMOD (intensive behavior program) | -8.1% vs -4.9% | 57% vs 43% | 35% vs 21% |
| COR-Diabetes (type 2 diabetes) | -3.7% vs -1.7% | 36% vs 18% | 15% vs 5% |
COR-I, published in The Lancet in 2010, enrolled 1,742 adults at 34 U.S. sites and was funded by Orexigen Therapeutics, the company that developed Contrave; its published analysis reported -6.1% vs -1.3%. COR-II, a fourth trial of 1,496 adults, reported -6.4% vs -1.2% at 56 weeks. In COR-Diabetes, HbA1c fell by 0.6 points vs 0.1 on placebo. One important caveat: 45% of the placebo group and 46% of the Contrave group left the trials before the 56 weeks were up, most of them within the first 12 weeks, and 24% of people on Contrave stopped because of side effects, twice the placebo rate.
The 12-week check on the label
Contrave is started low and increased gradually over the first weeks, taken in the morning and evening. The label says the tablets should not be cut, chewed or crushed, and should not be taken with a high-fat meal, because that significantly raises the amount of both drugs in the blood and with it the risk of seizures. The label also builds in a checkpoint: response should be judged after 12 weeks on the full maintenance level, and if a person has not lost at least 5% of starting body weight, Contrave should be stopped, because meaningful weight loss is then unlikely.
Contrave side effects
These are the most common Contrave side effects in the label’s placebo-controlled trials (2,545 people on Contrave, 1,515 on placebo):
| Side effect | Contrave | Placebo |
|---|---|---|
| Nausea | 32.5% | 6.7% |
| Constipation | 19.2% | 7.2% |
| Headache | 17.6% | 10.4% |
| Vomiting | 10.7% | 2.9% |
| Dizziness | 9.9% | 3.4% |
| Insomnia | 9.2% | 5.9% |
| Dry mouth | 8.1% | 2.3% |
| Diarrhea | 7.1% | 5.2% |
Nausea was the side effect that most often led people to stop (6.3%). In the one-year trials, sleep, mood and anxiety complaints together were reported by 22.2% on Contrave vs 15.5% on placebo, and people 65 and older reported them more often.
Boxed warning and other serious warnings
- Suicidal thoughts and behaviors (boxed warning): antidepressants such as bupropion raised this risk in children, teens and young adults in short-term trials. In Contrave’s obesity trials up to 56 weeks there were no suicides or attempts; suicidal thoughts were reported by 1 of 3,239 people on Contrave and 3 of 1,515 on placebo. Anyone starting it should be watched for new or worsening depression or unusual changes in mood or behavior.
- Seizures: bupropion can cause seizures; they occurred in about 0.1% of people on Contrave in trials vs none on placebo.
- Blood pressure and heart rate: both can rise, with the largest differences in the first 12 weeks, so they should be checked before and during use.
- Opioids: naltrexone blocks opioid pain medicines. Trying to overcome the block with large amounts of opioids can cause a fatal overdose, and people may be more sensitive to opioids after stopping Contrave.
- Liver injury linked to naltrexone, mania in people at risk of bipolar disorder, angle-closure glaucoma, serious allergic and skin reactions, and low blood sugar in people with type 2 diabetes on insulin or sulfonylureas.
Who should not take Contrave
- Uncontrolled high blood pressure.
- A seizure disorder or history of seizures, or a current or past diagnosis of anorexia or bulimia.
- Regular use of opioids, including methadone or buprenorphine, or opioid withdrawal.
- Suddenly stopping alcohol, benzodiazepines, barbiturates or seizure medicines.
- Use of an MAOI antidepressant now or in the past 14 days, or of linezolid or intravenous methylene blue.
- Use of any other bupropion product, or an allergy to any ingredient.
The label says weight loss offers no benefit during pregnancy and may harm the baby, so Contrave should be stopped when a pregnancy is recognized. Both drugs pass into breast milk.
Interactions and alcohol
Bupropion slows the breakdown of drugs handled by the liver enzyme CYP2D6, including some antidepressants, antipsychotics, the beta-blocker metoprolol and some heart rhythm drugs, so their amounts may need lowering. Contrave can lower digoxin levels and can cause nervous system side effects with levodopa or amantadine. The label says alcohol should be minimized or avoided, and notes that bupropion can cause a false-positive urine screening test for amphetamines.
The heart-safety question: the LIGHT trial and after
When it approved Contrave, the FDA required a large cardiovascular outcomes trial. The first, LIGHT, enrolled 8,910 adults at higher heart risk at 266 U.S. centers. After the company publicly released confidential early results in 2015, at a point when only a quarter of the planned events had occurred, the study’s academic leaders recommended stopping it, and it was ended in May 2015. The final report in JAMA in 2016 showed that the early, favorable result shrank by the halfway point (2.0% vs 2.3% of people with a major heart event) and concluded that the drug’s cardiovascular safety “remains uncertain”.
A second trial, CONVENE, began in December 2015 and was stopped in April 2016 when U.S. rights changed hands. A third, INFORMUS, run by Currax Pharmaceuticals, started in January 2024 with about 8,600 participants and is expected to finish in 2029. Until then, the label states that Contrave’s effect on heart disease and death has not been established.
Is there a generic Contrave?
When we checked Drugs@FDA in September 2026, Contrave was the only fully approved naltrexone and bupropion extended-release tablet. One generic application received tentative approval in November 2022, which is not final approval and does not allow the product to be sold. Separate naltrexone and bupropion tablets exist, but they are different products from Contrave’s extended-release combination. A pharmacist can confirm what is currently available.
How Contrave compares with other options
Contrave is one of several medicines approved for long-term weight management. Phentermine is older but approved only for a few weeks. GLP-1 medicines such as Wegovy and Zepbound are weekly injections that produced larger average losses in their own trials; what GLP-1 is explains them and GLP-1 side effects covers their risks. Our guides to Ozempic alternatives and appetite suppressants compare the options, and semaglutide vs tirzepatide compares the two leading GLP-1 drugs.
Frequently Asked Questions
What is Contrave?
Contrave is a prescription extended-release tablet containing naltrexone and bupropion. It is FDA-approved for long-term weight management in adults with obesity, or overweight plus a weight-related condition, alongside diet and physical activity.
What are the most common Contrave side effects?
Nausea (32.5% vs 6.7% on placebo), constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea, according to the label’s pooled trials.
Why does Contrave have a boxed warning?
Because it contains bupropion, an antidepressant. Antidepressants increased suicidal thoughts and behaviors in children, teens and young adults in short-term trials, so people taking it should be monitored for mood changes.
How much weight do people lose on Contrave?
In the label’s 56-week trials, average loss was 3.7% to 8.1% on Contrave vs 1.7% to 4.9% on placebo, depending on the trial. Results vary widely between people.
Can you drink alcohol on Contrave?
The label says alcohol should be minimized or avoided, and suddenly stopping heavy drinking while starting Contrave is a contraindication because of seizure risk.
Can you take Contrave with opioid pain medicine?
No for regular opioid use: it is contraindicated. Naltrexone blocks opioids, and taking large amounts to overcome the block can be fatal.
Peptide Labs does not sell these drugs. This article is general information, not medical advice. Read the Medication Guide or patient information that comes with a prescription, and ask a pharmacist or prescriber how this information applies to you.
Last reviewed September 2026.
Related guides: Ozempic Alternatives: FDA-Approved Options, OTC Facts and What to Avoid, Appetite Suppressants: Prescription Drugs, Natural Options and the Risks, Phentermine: What It Is, Side Effects and Safety Facts.