Contrave Guide
Contrave is a fixed-dose oral combination of naltrexone HCl 8 mg (an opioid receptor antagonist) and bupropion HCl 90 mg (a dopamine and norepinephrine reuptake inhibitor) formulated as an extended-release tablet for chronic weight management. It was FDA-approved September 10, 2014 and is currently marketed by Currax Pharmaceuticals (the U.S. SPL labeler of record is Nalpropion Pharmaceuticals LLC, a Currax subsidiary). Contrave is not a GLP-1 receptor agonist — it acts in the brain on appetite-regulating hypothalamic neurons and on the mesolimbic dopamine reward circuit. Average weight loss in the pivotal COR trials at the 32 mg / 360 mg daily maintenance dose was roughly 4-5% body weight at 56 weeks placebo-subtracted, substantially less than GLP-1s like Wegovy (~14.9%) or Zepbound (~22.5%), positioning Contrave as a lower-cost option for patients who cannot tolerate GLP-1 gastrointestinal side effects or who have co-occurring nicotine or alcohol use disorder where bupropion or naltrexone may offer secondary benefit.
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At a Glance
| Generic Name | Naltrexone hydrochloride / Bupropion hydrochloride |
| Brand Names | Contrave |
| FDA Status | FDA-approved for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity (September 10, 2014). Originally developed by Orexigen Therapeutics; Orexigen filed Chapter 11 in 2018 and the Contrave assets were acquired by Nalpropion Pharmaceuticals (a joint venture of Pernix Therapeutics and a Highbridge-led investor group). Nalpropion was subsequently rolled up into Currax Pharmaceuticals, which now markets Contrave in the United States. Not FDA-approved for pediatric use.[1] |
| Approval Date | September 10, 2014[1] |
How Contrave Works
Bupropion stimulates hypothalamic pro-opiomelanocortin (POMC) neurons, which release alpha-MSH to reduce appetite, but POMC neurons also release beta-endorphin, which feeds back onto mu-opioid receptors on the POMC neurons themselves and shuts them off — limiting the appetite-suppressing effect. Naltrexone, by blocking those mu-opioid receptors, disables that auto-inhibitory feedback loop and allows bupropion's POMC activation to persist longer and more strongly. The two agents together also modulate the mesolimbic dopamine reward circuit (ventral tegmental area to nucleus accumbens), which is thought to reduce food cravings and the hedonic drive to eat palatable foods.[2]
Dosing Schedule
Contrave uses a gradual dose escalation to minimize side effects. Always follow your prescriber's guidance and the current FDA label[1].
Side Effects
Common (≥5% and ≥1.5× placebo in pooled phase 3 trials): nausea (~32%), constipation (~19%), headache (~17%), vomiting (~10%), dizziness (~10%), insomnia (~9%), dry mouth (~8%), diarrhea (~7%). Serious (rare): seizures (risk increases at doses above 32/360 mg daily or with high-fat meals, which raise systemic exposure), increased blood pressure and heart rate (most pronounced in the first three months), hepatotoxicity, angle-closure glaucoma, severe allergic reactions, hyponatremia/SIADH, activation of mania in bipolar patients. Boxed warning: suicidal thoughts and behaviors — bupropion is a member of the antidepressant class and carries the class-wide boxed warning for increased risk of suicidal ideation in children, adolescents, and young adults; monitor all patients for emergence or worsening of depression and suicidality, especially during initiation and dose changes. Contraindicated in patients with uncontrolled hypertension, seizure disorders, anorexia or bulimia, chronic opioid use (naltrexone will precipitate withdrawal), abrupt discontinuation of alcohol or benzodiazepines, current or recent (within 14 days) MAOI use, or pregnancy.[1][2]
This is not a complete list. Consult your healthcare provider or prescriber for full safety information. The complete adverse reaction profile is published in the current FDA prescribing information[1].
Clinical Trial Results
Contrave's FDA approval was supported by four pivotal 56-week phase 3 trials in the Contrave Obesity Research (COR) program. COR-I (Greenway FL et al., Lancet 2010, PMID 20673995; N=1,742 adults with BMI 30-45, or BMI 27-45 with dyslipidemia or hypertension) showed mean weight loss of 6.1% with naltrexone SR 32 mg / bupropion SR 360 mg versus 1.3% with placebo, and 48% of patients on the maintenance dose lost ≥5% body weight vs 16% on placebo. COR-II (Apovian CM et al., Obesity 2013, PMID 23408728; N=1,496) confirmed the COR-I efficacy in a second randomized trial of the 32/360 mg dose, with mean weight loss of 6.4% versus 1.2% placebo and 50.5% achieving ≥5% loss versus 17.1%. COR-Diabetes (Hollander P et al., Diabetes Care 2013, PMID 24144653; N=505 adults with type 2 diabetes) showed 5.0% weight loss vs 1.8% placebo plus a 0.6 percentage-point greater HbA1c reduction at 56 weeks. COR-BMOD (Wadden TA et al., Obesity 2011, PMID 20559296; N=793) tested Contrave layered onto an intensive behavior-modification program and produced 9.3% weight loss vs 5.1% with placebo plus behavior modification — the largest absolute weight-loss effect in the COR program, attributable to the added behavioral arm. Across all four trials, placebo-subtracted weight loss was approximately 4-5% body weight, substantially below the 11-15% placebo-subtracted weight loss seen in modern GLP-1 trials (STEP-1, SURMOUNT-1).[2]
Where to Get Contrave
These telehealth providers offer access to naltrexone hydrochloride / bupropion hydrochloride or compounded equivalents with online consultations and home delivery.
Editorial score · methodology
Editorial score · methodology
Enhance MD
Best for: lab-monitored compounded GLP-1 with mandatory video visit
Editorial score · methodology
Editorial score · methodology
Editorial score · methodology
Pallas Health
Best for: the most complete public disclosure of pharmacies and prescribing physicians we have found
Editorial score · methodology
Cost Comparison
Starting prices for compounded GLP-1 medications from top providers, sorted cheapest first. Compounded naltrexone hydrochloride / bupropion hydrochloride from licensed 503A and 503B pharmacies is legal under federal compounding law[3], with additional tolerances historically allowed while the molecule has appeared on the FDA Drug Shortage List[4]. Both compounded and brand-name prescriptions are generally FSA/HSA eligible under IRS Publication 502[5]. Prices may vary based on dose and promo availability.
Contrave Head-to-Head Comparisons
Short-form verdict pages comparing Contrave to other GLP-1 options with trial-anchored data, FDA-label dosing, and current manufacturer pricing.
See all drug-vs-drug verdicts.
Related Research on Contrave
Deep-dive articles from our research desk with primary-source trial data, FDA label verification, and editorial analysis.
Frequently Asked Questions
Sources & methodology — as of August 2026
- 1.FDA — Wegovy (semaglutide) Approval History via Drugs@FDA— U.S. Food & Drug Administration.
- 2.STEP 1 Trial — Once-Weekly Semaglutide in Adults with Overweight or Obesity (Wilding JPH et al.)— New England Journal of Medicine.PMID: 33567185.
- 3.FDA — Compounding and the 503A Pharmacy Framework— U.S. Food & Drug Administration.
- 4.FDA — Drug Shortages Database (current shortage listings)— U.S. Food & Drug Administration.
- 5.IRS Publication 502 — Medical and Dental Expenses (HSA/FSA eligibility)— Internal Revenue Service.