Contrave is an FDA-approved oral combination of naltrexone and bupropion that produces 5 to 9 percent body weight loss at one year. It works by reducing appetite and food cravings through hypothalamic POMC neurons and reward pathways. It is approved for adults with a BMI of 30 or higher, or 27 or higher with a weight-related condition. Common side effects are nausea, constipation, headache, and insomnia.
What Contrave Is
Contrave is a fixed-dose extended-release tablet containing:
- Naltrexone 8 mg — a mu-opioid receptor antagonist used at higher doses for alcohol and opioid use disorder.
- Bupropion 90 mg — a norepinephrine-dopamine reuptake inhibitor used as an antidepressant (Wellbutrin) and smoking cessation aid (Zyban).
The FDA approved Contrave in September 2014 for chronic weight management. It is manufactured by Currax Pharmaceuticals (formerly Orexigen and Nalpropion).
Who Qualifies
Contrave is indicated for adults who, alongside a reduced-calorie diet and increased physical activity, have one of:
- BMI of 30 kg/m² or higher
- BMI of 27 kg/m² or higher with at least one weight-related condition (hypertension, type 2 diabetes, dyslipidemia, sleep apnea)
It is not approved for use in children or adolescents.
How It Works
Bupropion stimulates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. POMC firing reduces appetite. However, POMC neurons secrete beta-endorphin, which feeds back to inhibit their own firing — a negative loop that normally limits how much appetite suppression bupropion can produce. Naltrexone blocks that feedback at mu-opioid receptors, allowing bupropion’s POMC stimulation to persist longer. The combined effect is greater than either drug alone.
The two ingredients also act in mesolimbic reward circuits, potentially reducing reward-driven and emotional eating.
Dosing Schedule
Contrave is titrated up over 4 weeks to reduce nausea.
| Week | Morning | Evening | Total Daily Dose |
|---|---|---|---|
| 1 | 1 tablet | — | 8/90 mg |
| 2 | 1 tablet | 1 tablet | 16/180 mg |
| 3 | 2 tablets | 1 tablet | 24/270 mg |
| 4+ | 2 tablets | 2 tablets | 32/360 mg (maintenance) |
Tablets are taken with food but not with high-fat meals (which substantially increase bupropion absorption and may trigger seizures). Tablets must be swallowed whole — crushing increases peak levels and seizure risk.
Evaluate response at 12 weeks on the maintenance dose. If less than 5 percent body weight loss has been achieved, discontinue — continued benefit is unlikely.
Expected Weight Loss
Four pivotal trials (COR-I, COR-II, COR-BMOD, COR-Diabetes) supported approval.
| Trial | Population | Mean Weight Loss at 1 Year | ≥5% Loss |
|---|---|---|---|
| COR-I | BMI 30-45 (or 27+ with comorbidity) | 6.1% (Contrave) vs 1.3% (placebo) | 48% |
| COR-II | Similar to COR-I | 6.4% vs 1.2% | 50% |
| COR-BMOD | Plus intensive behavior therapy | 9.3% vs 5.1% | 66% |
| COR-Diabetes | Adults with T2D | 5.0% vs 1.8% | 44% |
Patients on Contrave also saw improvements in HDL, triglycerides, waist circumference, fasting insulin, and (in COR-Diabetes) HbA1c.
Common Side Effects
The most frequent adverse effects, especially during titration, are:
- Nausea — 32% (most common reason for discontinuation)
- Constipation — 19%
- Headache — 18%
- Vomiting — 11%
- Dizziness — 10%
- Insomnia — 9%
- Dry mouth — 8%
- Diarrhea — 7%
Nausea usually peaks at week 3 to 4 and improves over time. Taking each dose with a small low-fat meal helps. Slower titration is an option for sensitive patients.
Serious Risks
- Suicidal thoughts and behavior — bupropion class boxed warning, primarily for patients up to age 24. Monitor mood, especially in the first months.
- Seizures — bupropion lowers seizure threshold. Risk roughly 0.1% at the recommended dose; higher with predisposing factors.
- Acute opioid withdrawal — patients who use opioids regularly will go into withdrawal because of naltrexone. Stop opioids at least 7 to 10 days before starting Contrave.
- Blood pressure and heart rate — small increases possible. Recheck after initiation.
- Hepatotoxicity — rare; stop for jaundice, abdominal pain, or transaminase elevation.
- Angle-closure glaucoma — bupropion can precipitate in susceptible eyes.
- Hypoglycemia — when combined with insulin or sulfonylureas, dose adjustments may be needed.
Contraindications
- Uncontrolled hypertension
- Seizure disorder or history of seizures
- Bulimia or anorexia nervosa
- Chronic opioid use, opioid agonist treatment (methadone, buprenorphine), or acute opioid withdrawal
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptics
- MAOI use within 14 days
- Pregnancy
- Hypersensitivity to either component
How Contrave Compares
| Medication | Class | Average Weight Loss (1 yr) | Notable Considerations |
|---|---|---|---|
| Contrave | Naltrexone + bupropion | ~5-9% | Helps reward-driven eating; not stimulant |
| Qsymia | Phentermine + topiramate | ~8-10% | More effective; stimulating; teratogenic |
| Phentermine alone | Sympathomimetic | ~5-8% | Cheap; short-term label |
| Orlistat | Lipase inhibitor | ~3-4% | GI side effects; OTC available |
| Wegovy | GLP-1 RA | ~15% | Injectable; more effective |
| Zepbound | GIP/GLP-1 | ~21% | Injectable; most effective |
Cardiovascular Outcomes — the LIGHT Trial Controversy
The LIGHT trial was a post-marketing cardiovascular outcomes study mandated by the FDA. It was terminated early after the manufacturer released interim results without authorization. The full data did not demonstrate major adverse cardiovascular events at rates different from placebo, but the early termination left the cardiovascular safety question incompletely answered. Clinicians often avoid Contrave in patients with high cardiovascular risk; modest blood pressure and heart rate effects support monitoring.
Cost and Access
Contrave is brand-only. Cash retail price is roughly $700 per month, but a manufacturer direct-to-consumer program runs about $99 per month. Many insurance plans cover with prior authorization. Medicare Part D historically excludes anti-obesity drugs.
Practical Considerations
- Take with food, but avoid high-fat meals.
- Swallow tablets whole — no crushing, splitting, or chewing.
- Tolerance to nausea typically develops by week 5 to 6.
- If you take opioids for any reason (chronic pain, post-surgical), Contrave is not appropriate during opioid use.
- Plan for blood pressure rechecks early in treatment.
- Combine with diet, exercise, and behavioral support — medication alone underperforms its trial numbers.
Related Reading
For broader context, see our anti-obesity medications overview, our guides on Qsymia and Plenity, and our pillar on treatment options.
The Bottom Line
Contrave is a twice-daily oral combination of naltrexone and bupropion that produces 5 to 9 percent body weight loss at one year by reducing appetite and food cravings. It is approved for adults with BMI 30 or higher, or 27 or higher with a weight-related condition. Common side effects are nausea, constipation, headache, and insomnia; serious concerns include seizure risk, opioid incompatibility, and a boxed warning for suicidality in younger adults. Talk to your doctor about your full medical history and medication list before starting, and combine Contrave with sustained lifestyle change to maximize long-term results.
