Contrave combines naltrexone (an opioid-receptor antagonist) with bupropion (a dopamine/noradrenaline reuptake inhibitor). Together they act on the brain's appetite and reward pathways to reduce hunger and food cravings. Its average weight loss is modest — below the GLP-1 drugs — and it is contraindicated in seizure disorders and in people using opioids.
Obesity Medication Library entry. Section accent: family --teal.
DRUG FACT PANEL
| Generic | Naltrexone / bupropion extended-release |
| Brand | Contrave |
| Class | Fixed combination: opioid-receptor antagonist (naltrexone) + dopamine/noradrenaline reuptake inhibitor (bupropion) |
| Mechanism (1 line) | Acts on brain appetite and reward circuits (hypothalamic and mesolimbic) to reduce hunger and food cravings |
| FDA indication | Chronic weight management in adults with obesity, or overweight with a weight-related condition |
| Who it's for | Adults with reward- or craving-driven eating; those who also benefit from bupropion's effects; not for people with seizure disorders or on opioids |
| Route/formulation | Oral tablet, taken daily (titrated up over weeks) |
| Titration concept | Started at a low dose and stepped up over about a month to limit nausea — individual dosing is set by a clinician, not this page |
| Expected effect | Modest — roughly ~5–6% total body-weight loss (about ~4.8% placebo-subtracted) over ~1 year in the COR trials, with lifestyle; below the GLP-1 drugs and below Qsymia |
| Evidence level (obesity) | Grade A 🟢 — RCTs (COR program) + guideline support; modest efficacy |
What Contrave is
Contrave is a fixed oral combination of two existing drugs: bupropion (used for depression and smoking cessation) and naltrexone (used for alcohol and opioid dependence). Neither was a weight-loss drug alone, but together they act on the brain circuits that govern appetite and the rewarding, craving quality of eating — which makes Contrave a distinctive option for people whose eating is driven more by reward and cravings than by simple hunger. → Food Noise
How it works
The combination targets two linked brain systems:
- Bupropion stimulates POMC neurons in the hypothalamus (an appetite-regulating hub) and raises dopamine/noradrenaline signalling.
- Naltrexone blocks an opioid-mediated feedback loop that would otherwise switch those POMC neurons off, so the appetite effect is sustained; it also dampens the reward value of food in mesolimbic circuits.
The net effect is reduced hunger and fewer cravings. This is a different mechanism from the incretin drugs and from stimulant appetite suppression — closer to the "reward and food-noise" side of eating behaviour. → Mental Health & Obesity
What the trials actually show
Contrave's approval rests on the randomised COR program (Contrave Obesity Research), which showed weight loss greater than placebo over about a year, often paired with behavioural support. Across the COR trials (about a year, with behavioural support), average loss was on the order of ~5–6% of total body weight — roughly ~4.8% after subtracting placebo. In the efficacy ranking of approved drugs, Contrave is in the modest tier — below semaglutide and tirzepatide, and generally below Qsymia. Some patients respond well, particularly when craving-driven eating is the main driver, but that figure is a trial average, not a personal prediction. → Semaglutide
Side effects
Common: nausea (the most frequent, hence slow titration), constipation, headache, dizziness, insomnia, dry mouth, and increased blood pressure or heart rate.
Less common / serious: - Seizure risk — bupropion lowers the seizure threshold; this is a central safety concern. - Neuropsychiatric effects — bupropion carries a boxed warning regarding mood, behaviour and suicidal thoughts, particularly relevant in younger patients; mood should be monitored. - Blood-pressure elevation, and rare hepatotoxicity considerations with naltrexone at higher doses.
Contraindications & cautions
- Seizure disorder (or conditions/medications that lower the seizure threshold) — contraindicated.
- Chronic opioid use, or opioid dependence / acute opioid withdrawal — contraindicated; naltrexone blocks opioid analgesia and can precipitate withdrawal.
- Uncontrolled hypertension — caution/contraindicated.
- Eating disorders (bulimia or anorexia nervosa) — bupropion is contraindicated (higher seizure risk).
- Recent/concurrent MAO inhibitors — contraindicated.
- Pregnancy — not recommended (see below).
Monitoring, pregnancy and surgery
- Monitoring: blood pressure and heart rate; mood and behaviour (neuropsychiatric boxed warning); seizure risk factors; response and GI tolerance.
- Pregnancy/lactation: not recommended in pregnancy; discontinue if pregnancy is planned or confirmed. → Women's Health & Obesity
- Perioperative: if opioid analgesia will be needed for surgery, the naltrexone component is a critical consideration — coordinate with the surgical/anaesthesia and pain teams in advance.
Long-term considerations, discontinuation and weight regain
Contrave treats a chronic condition, and its benefit depends on continued use — stopping is typically followed by regain, as with every effective obesity drug. A common clinical rule is to reassess early: if a patient has not achieved a meaningful response after an adequate trial, continuing is usually not worthwhile. Because of the bupropion component, mood should be monitored around both starting and stopping. Maintenance should be planned before starting. → Weight Regain & Maintenance
Unanswered questions
- Which patients (by eating behaviour or psychology) respond best.
- Long-term cardiovascular safety profile.
- Its place relative to incretins for craving-predominant eating.
Questions patients ask
How does Contrave work?
It combines naltrexone and bupropion to act on the brain's appetite and reward circuits, reducing hunger and food cravings — a different mechanism from GLP-1 drugs or stimulants. Grade A 🟢 → Food Noise
How much weight will I lose on Contrave?
On average, modest — below the GLP-1 drugs and generally below Qsymia. Some people with craving-driven eating respond better than the average suggests. Grade A 🟢
Who shouldn't take it?
People with a seizure disorder, those using opioids, uncontrolled hypertension, or bulimia/anorexia — all contraindications, mainly because bupropion lowers the seizure threshold. Grade A 🟢
Can I take Contrave if I take pain medication?
Not if that includes opioids — naltrexone blocks opioid effects and can precipitate withdrawal. Tell every clinician you take it, especially before surgery. Grade A 🟢
Does it affect mood?
It can — the bupropion component carries a boxed warning about mood, behaviour and suicidal thoughts, so mood should be monitored, especially in younger patients. Grade A 🟢 → Mental Health & Obesity
Will I regain weight if I stop?
Usually yes — it treats a chronic disease, so stopping is typically followed by regain. Clinicians also reassess early and stop it if there's no meaningful response. Grade A 🟢 → Weight Regain & Maintenance
KEEP READING
- Obesity Medication Library — where Contrave ranks among all approved options.
- Food Noise — the reward-and-craving biology Contrave targets.
- Mental Health & Obesity — eating behaviour, mood and medication choice.
- Semaglutide — the higher-efficacy incretin comparison.
- Weight Regain & Maintenance — the "forever" question, for any obesity drug.
Written by Darius A. Schneider, MD, PhD · Board-Certified Endocrinologist (ECNU) · Last updated: 2026-08-10 · References: Contrave FDA prescribing information; COR (Contrave Obesity Research) program; bupropion neuropsychiatric labeling. Not individualized medical advice.
