Naltrexone for Weight Loss: How Contrave Works

12 MIN READ • BY The BodySpec Team • Nov 25, 2025

A white pill lies on a light wooden surface in the foreground, with a bowl of vibrant green salad, including lettuce, tomatoes, cucumbers, and red onion, blurred in the background. The scene suggests a combination of medication and healthy eating for wellness.

Naltrexone for Weight Loss: How Contrave Works (2025)

Curious about naltrexone for weight loss? Here’s the short version: Contrave (naltrexone/bupropion ER) is an oral, FDA‑approved option that helps many adults lose about 5–10% of their body weight in a year when paired with healthy habits. It’s not as potent as GLP‑1s on average, but it’s a pill, widely used, and may be a fit if you prefer non‑injection options or can’t access GLP‑1s.

Quick note: Contrave is the only FDA‑approved way naltrexone is used for chronic weight management; it combines naltrexone (an opioid receptor blocker) with bupropion (an antidepressant/smoking‑cessation medicine). It’s prescribed alongside nutrition, activity, and behavior change—not as a standalone fix (Cleveland Clinic, 2024; MedlinePlus, 2024).

Key takeaways

What it is: Contrave (naltrexone/bupropion ER) is an oral, FDA‑approved weight‑management medicine used with lifestyle changes.
Expected results: Typical loss is about 5–10% of body weight over 6–12 months in trials; real‑world averages are closer to ~4% at 6 months (Pharmacy & Therapeutics, 2016; Clinical Obesity, 2024).
How it compares: Average loss is smaller than GLP‑1s (e.g., one NMA: ~4.6% with NB vs ~13.7% with semaglutide), but it’s a pill and may fit better for some people (JMCP, 2023; Endotext/NCBI, 2024).
Safety snapshot: Avoid with seizure disorders, uncontrolled hypertension, active eating disorders, chronic opioid use, or within 14 days of MAOIs. Take exactly as prescribed; avoid high‑fat meals to reduce seizure risk (MedlinePlus, 2024; Medscape, 2025; Cleveland Clinic, 2024).
Maximizing results: Pair with a structured plan and track fat vs muscle with DEXA so you’re losing fat—not muscle. Start here: Why body composition beats scale weight and DEXA for visceral fat: accuracy, cost, results.

How naltrexone/bupropion helps with weight loss

An illustration of a see-saw with a brain balancing in the middle. On the left, an upward arrow and the text 'ENERGY UP'. On the right, a downward arrow and the text 'CRAVINGS DOWN'.

Think of appetite control as a push‑pull system:

Bupropion “pushes the gas” on POMC neurons in the hypothalamus—curbing appetite and nudging up energy expenditure.
Naltrexone “releases the brake” by blocking opioid receptors that normally dampen those POMC signals—reducing cravings from the brain’s reward circuits.

Together, they can reduce hunger and food‑seeking behavior more than either alone (Pharmacy & Therapeutics, 2016).

Can you take naltrexone alone for weight loss?

Evidence for naltrexone monotherapy in obesity is limited and inconsistent; the strongest evidence for weight loss is with the fixed‑dose combination with bupropion (Obesity Reviews, 2021).

What the evidence says (and what to expect)

Clinical trials: Across four pivotal phase 3 trials, Contrave produced significant weight loss vs placebo over 56 weeks; lifestyle coaching amplified results (Pharmacy & Therapeutics, 2016).
Real‑world data: A 6‑month clinic study found an average ~4% loss, with 42.5% reaching ≥5% loss; slower titration and adherence likely explain gaps vs RCTs (Clinical Obesity, 2024).
Mood considerations: In adults with obesity and mild‑to‑moderate depression, NB led to ~5.7% loss at 56 weeks without worsening depression vs placebo (Healio, 2025).

How it stacks up to GLP‑1s: Network meta‑analysis suggests average loss with bupropion/naltrexone is smaller than semaglutide or tirzepatide. But the oral route, different side‑effect profile, and potential insurance access can make it the right fit for some patients (JMCP, 2023; Endotext/NCBI, 2024). For a broader overview of non‑GLP‑1 options, see Ozempic alternatives: complete 2025 guide.

Who is (and isn’t) a good candidate

FDA indication: Adjunct to a reduced‑calorie diet and increased physical activity for adults with BMI ≥30, or BMI ≥27 with a weight‑related condition (e.g., hypertension, dyslipidemia, type 2 diabetes) (MedlinePlus, 2024).

Do not use if you:

Have a seizure disorder or history of seizures
Have uncontrolled high blood pressure
Have bulimia or anorexia nervosa
Use chronic opioids or are in acute opioid withdrawal
Used an MAOI within 14 days
Are pregnant

Use caution and discuss risks if you have a history of bipolar disorder, significant head injury, stroke, liver disease, narrow‑angle glaucoma, or if you’re reducing alcohol or sedative use. Monitor blood pressure, mood, sleep, and blood sugar if diabetic (MedlinePlus, 2024; Medscape, 2025; Cleveland Clinic, 2024).

Good‑fit scenarios to discuss with your clinician:

You prefer an oral option or cannot access GLP‑1s
You already take bupropion for depression/smoking cessation and want a weight‑centric plan
You experience strong cravings/reward‑driven eating patterns

Dosing: a safe, step‑up titration

To reduce side effects and seizure risk, Contrave uses a 4‑week titration. Avoid high‑fat meals. Do not exceed the max daily dose of 32 mg naltrexone/360 mg bupropion (2 tablets twice daily). Always follow your prescriber’s instructions (MedlinePlus, 2024; Medscape, 2025).

Week	Morning	Evening
1	1 tablet (8 mg/90 mg)	—
2	1 tablet	1 tablet
3	2 tablets	1 tablet
4+ (target)	2 tablets	2 tablets

Dose limits (examples; your prescriber will personalize):

Moderate/severe renal impairment or moderate hepatic impairment: Do not exceed two tablets daily (one in the morning and one in the evening) (Medscape, 2025).
With strong CYP2B6 inhibitors: Max 1 tablet twice daily (Medscape, 2025).

When to reassess: If you haven’t lost ≥5% of starting weight by 12–16 weeks at maintenance dose, most guidelines recommend stopping and considering alternatives (Pharmacy & Therapeutics, 2016; MedlinePlus, 2024).

An illustration showing a half-blue, half-white capsule pill next to a hamburger and french fries with a red 'X' over them, signifying not to combine the two. The food is within a light green circle background, contrasting with the pill on a plain white background.

Side effects and safety watch‑outs

Common effects: nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea (MedlinePlus, 2024; Cleveland Clinic, 2024).

A woman with short, curly dark hair sits on a beige couch, holding her stomach with both hands and looking down with a pained expression. She appears to be experiencing stomach discomfort, possibly nausea. A glass of water is visible on a small round table next to her.

Serious risks to discuss and monitor:

Seizures (dose‑related; respect titration and meal guidance)
Increases in blood pressure and heart rate
Mood changes or suicidal thoughts (bupropion has an antidepressant class warning)
Hepatotoxicity symptoms (e.g., right‑upper quadrant pain, dark urine, jaundice)
Acute angle‑closure glaucoma
Opioid interactions and overdose risk if trying to “override” blockade after stopping

Seek urgent care for signs of severe allergic reactions or severe skin reactions (e.g., blistering rash) (MedlinePlus, 2024; Cleveland Clinic, 2024; Medscape, 2025).

Alcohol: Avoid heavy drinking and abrupt cessation while on therapy; both can increase seizure risk (Cleveland Clinic, 2024).

Antidepressants: NB can be used with certain antidepressants but requires careful dose management and monitoring for neuropsychiatric effects (see interactions in Medscape, 2025). If you have depression or anxiety, review a monitoring plan with your clinician; a 2025 analysis did not show worsening depression on NB vs placebo in mild‑to‑moderate cases (Healio, 2025).

How to make results stick (and protect your muscle)

A happy, smiling interracial couple walking on a path in a sunny park with green trees and grass, looking active and healthy.

Medication can make calorie and craving control easier—but sustainable change still comes from consistent habits. Two tips to maximize outcomes:

Pair NB with structured nutrition, movement, and behavior supports. If insulin resistance is part of your picture, this guide can help: Insulin resistance and weight loss.
Track more than scale weight. Use DEXA to see how fat mass, lean mass, and visceral fat change as you lose weight. Preserving muscle supports your metabolism and long‑term maintenance. Learn more: The most accurate body composition tests and How to prevent lean mass loss on weight‑loss meds.

Consider this: Book periodic scans to calibrate your plan—if lean mass drops too quickly, increase protein, adjust training, and review dosing/timing with your clinician.

Key discussion points for your doctor

An illustration of a clipboard with a checklist for health monitoring. The checklist includes icons for heart health, brain health, and weight, each with a green checkmark indicating completion.

Screen: BMI criteria, comorbidities, seizure risk, BP control, mood history, opioid use, eating disorders, glaucoma risk
Plan: 4‑week titration; avoid high‑fat meals; set a 12–16 week response checkpoint (≥5% loss)
Monitor: BP/HR, mood/sleep, adverse effects, blood glucose (if T2D), and body composition (lean mass preservation)
Support: Nutrition, resistance training, sleep, and behavior strategies; consider DEXA at baseline and intervals to quantify fat vs muscle change (DEXA for visceral fat)