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> Reviewed by FormBlends Medical Team · Last updated April 2026 · 14 sources cited
Key Takeaways
- Each Contrave tablet contains exactly 8 mg naltrexone hydrochloride and 90 mg bupropion hydrochloride extended-release
- The full maintenance dose is two tablets twice daily, totaling 32 mg naltrexone and 360 mg bupropion per day
- This naltrexone dose is 84% lower than the 50 mg dose used for opioid or alcohol dependence, targeting different brain pathways
- The combination works through the hypothalamic POMC/beta-endorphin reward circuit, not through addiction-receptor blockade
Direct answer (40-60 words)
Each Contrave tablet contains 8 mg naltrexone hydrochloride combined with 90 mg bupropion hydrochloride in an extended-release formulation. At the full maintenance dose of four tablets daily (two tablets twice daily), patients receive 32 mg naltrexone total per day. This is substantially lower than the 50 to 100 mg doses used for opioid or alcohol addiction treatment.
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- The exact naltrexone content in each Contrave tablet
- Why 8 mg is the dose: the POMC neuron mechanism
- How Contrave's naltrexone dose compares to addiction treatment doses
- The full titration schedule and total daily naltrexone exposure
- What most articles get wrong about low-dose naltrexone
- The bupropion-naltrexone synergy: why neither works alone
- Clinical data on the dose-response relationship
- When the 8 mg dose causes opioid-receptor effects anyway
- Contrave vs GLP-1 medications: different mechanisms, different outcomes
- The decision tree: is Contrave's naltrexone dose right for you?
- FAQ
- Footer disclaimers
The exact naltrexone content in each Contrave tablet
Contrave is manufactured as a single fixed-dose combination tablet. Each tablet contains:
- 8 mg naltrexone hydrochloride
- 90 mg bupropion hydrochloride
- Extended-release formulation (12-hour release profile)
The tablet is not scored and cannot be split. There is no half-strength or double-strength version. The 8 mg/90 mg ratio is the only formulation approved by the FDA.
At the full maintenance dose, patients take:
- Morning: 2 tablets (16 mg naltrexone, 180 mg bupropion)
- Evening: 2 tablets (16 mg naltrexone, 180 mg bupropion)
- Daily total: 32 mg naltrexone, 360 mg bupropion
The extended-release formulation means naltrexone is released gradually over 12 hours, maintaining steady plasma levels rather than the peak-and-trough pattern seen with immediate-release naltrexone.
Why 8 mg is the dose: the POMC neuron mechanism
The 8 mg naltrexone dose in Contrave was not chosen arbitrarily. It targets a specific brain circuit that has nothing to do with opioid addiction.
Here's the mechanism:
Step 1: Bupropion activates POMC neurons. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI). In the hypothalamus, it stimulates pro-opiomelanocortin (POMC) neurons. These neurons are the brain's primary appetite-regulation cells.
Step 2: POMC neurons release two signals. When activated, POMC neurons release:
- Alpha-MSH (alpha-melanocyte-stimulating hormone): This binds to MC4 receptors and suppresses appetite. This is the signal you want.
- Beta-endorphin: This is an endogenous opioid that binds to mu-opioid receptors and creates a feedback loop that turns POMC neurons back off. This is the signal you don't want.
Step 3: Naltrexone blocks the beta-endorphin feedback. At 8 mg, naltrexone blocks just enough mu-opioid receptors to prevent beta-endorphin from shutting down the POMC neurons. This keeps the alpha-MSH signal going longer, which sustains appetite suppression.
The dose is calibrated to block the autoinhibitory feedback loop without causing full opioid-receptor antagonism. At 50 mg (the addiction-treatment dose), naltrexone blocks nearly all mu-opioid receptors throughout the body. At 8 mg, it selectively modulates the hypothalamic circuit.
This mechanism was first described by Greenway et al. in the COR-I trial publication (Lancet, 2010) and confirmed in receptor-binding studies by Cowley et al. (Journal of Clinical Investigation, 2001).
How Contrave's naltrexone dose compares to addiction treatment doses
| Indication | Naltrexone dose | Receptor occupancy | Primary mechanism |
|---|---|---|---|
| Contrave (weight loss) | 8 mg twice daily (16 mg/day titration, 32 mg/day maintenance) | ~30-40% mu-opioid receptor blockade | POMC neuron disinhibition |
| Opioid use disorder | 50 mg once daily | ~95% mu-opioid receptor blockade | Complete opioid antagonism |
| Alcohol use disorder | 50 mg once daily or 380 mg monthly injection (Vivitrol) | ~95% mu-opioid receptor blockade | Reward pathway disruption |
| Low-dose naltrexone (off-label) | 1.5 to 4.5 mg once daily | ~10-20% receptor blockade | Proposed endorphin rebound effect |
The 8 mg dose in Contrave sits in a middle zone. It's higher than the "low-dose naltrexone" used off-label for autoimmune conditions but far lower than addiction-treatment doses.
Critically, the 8 mg dose does not cause precipitated withdrawal in opioid-dependent patients the way 50 mg does, but it still contraindicates Contrave in anyone taking opioid pain medication. Even partial receptor blockade will reduce opioid efficacy.
The full titration schedule and total daily naltrexone exposure
Contrave is titrated over four weeks to reduce the risk of nausea, headache, and dizziness. The FDA-approved schedule is:
| Week | Morning dose | Evening dose | Daily naltrexone total | Daily bupropion total |
|---|---|---|---|---|
| Week 1 | 1 tablet | None | 8 mg | 90 mg |
| Week 2 | 1 tablet | 1 tablet | 16 mg | 180 mg |
| Week 3 | 2 tablets | 1 tablet | 24 mg | 270 mg |
| Week 4+ | 2 tablets | 2 tablets | 32 mg | 360 mg |
Most patients reach the full maintenance dose (32 mg naltrexone daily) by week 4. Some providers hold at week 3 dosing (24 mg naltrexone daily) if side effects are bothersome, though the clinical trial data supporting efficacy is strongest at the full 32 mg dose.
The titration is driven primarily by bupropion tolerability (nausea, headache, insomnia) rather than naltrexone side effects. Naltrexone at 8 mg per tablet is generally well-tolerated from day one.
What most articles get wrong about low-dose naltrexone
Most articles conflate Contrave's 8 mg naltrexone dose with "low-dose naltrexone" (LDN), the 1.5 to 4.5 mg off-label regimen used for autoimmune conditions, fibromyalgia, and chronic pain. This is incorrect.
The error: LDN proponents theorize that very low doses (1.5 to 4.5 mg) cause a brief opioid-receptor blockade that triggers a rebound increase in endogenous endorphin production 4 to 6 hours later. This rebound effect is thought to modulate immune function and reduce inflammation.
Why Contrave is different: Contrave uses 8 mg twice daily (16 mg per dose, 32 mg daily total) in an extended-release formulation. This maintains continuous receptor blockade for 12+ hours. There is no rebound window. The mechanism is sustained POMC disinhibition, not endorphin rebound.
The two regimens target different pathways:
- LDN (1.5 to 4.5 mg): Proposed endorphin rebound, immune modulation (limited evidence, mostly case series)
- Contrave (8 mg twice daily): Sustained mu-opioid blockade in hypothalamus, appetite suppression (four Phase 3 RCTs, FDA-approved)
Calling Contrave "low-dose naltrexone" is technically true relative to 50 mg addiction doses, but it misleads patients into thinking the mechanisms are the same. They are not.
The bupropion-naltrexone synergy: why neither works alone
The 8 mg naltrexone dose only works in combination with bupropion. Neither component produces meaningful weight loss as monotherapy at these doses.
The evidence:
Bupropion alone (300 to 400 mg/day): In a 24-week trial, bupropion monotherapy produced 5.0% weight loss vs 1.8% placebo. Modest effect, not clinically significant by FDA standards (Gadde et al., Obesity Research, 2001).
Naltrexone alone (16 to 50 mg/day): In a 12-week trial, naltrexone monotherapy produced 1.2% weight loss vs 0.8% placebo. No meaningful effect (Atkinson et al., International Journal of Obesity, 1985).
Bupropion + naltrexone (360 mg/32 mg): In the COR-I trial, the combination produced 8.1% weight loss at 56 weeks vs 1.8% placebo (Greenway et al., Lancet, 2010). In COR-II, 9.3% vs 1.2% placebo (Apovian et al., Obesity, 2013).
The synergy is real and reproducible. Bupropion activates POMC neurons. Naltrexone prevents them from shutting back down. Remove either component and the circuit fails.
This is different from GLP-1 receptor agonists like semaglutide or tirzepatide, which work through a completely separate mechanism (incretin-mediated appetite suppression and delayed gastric emptying). GLP-1s do not require a second agent to function.
Clinical data on the dose-response relationship
The four phase 3 Contrave trials (COR-I, COR-II, COR-BMOD, COR-Diabetes) all used the same fixed dose: 32 mg naltrexone and 360 mg bupropion daily. There is limited published data on lower or higher naltrexone doses in combination with bupropion.
One dose-finding study (Greenway et al., Obesity, 2009) compared:
- Naltrexone 16 mg + bupropion 360 mg
- Naltrexone 32 mg + bupropion 360 mg
- Naltrexone 48 mg + bupropion 360 mg
Results at 24 weeks:
- 16 mg naltrexone: 6.1% weight loss
- 32 mg naltrexone: 8.9% weight loss
- 48 mg naltrexone: 9.2% weight loss
The 32 mg dose hit the inflection point. Increasing to 48 mg added minimal benefit but increased nausea and dizziness. The 16 mg dose (half the maintenance dose, equivalent to stopping titration at week 2) was less effective.
This data supports the current FDA-approved regimen. The 8 mg-per-tablet formulation allows titration to the optimal 32 mg daily dose without requiring patients to take more than four tablets per day.
When the 8 mg dose causes opioid-receptor effects anyway
Even at 8 mg twice daily, naltrexone in Contrave can cause clinically significant opioid-receptor blockade in specific situations:
1. Patients taking prescription opioids. Contrave is contraindicated in anyone taking opioid pain medication (oxycodone, hydrocodone, morphine, tramadol, etc.). Even 8 mg naltrexone will reduce opioid efficacy and may precipitate withdrawal in opioid-dependent patients.
2. Patients undergoing surgery or acute pain management. Contrave must be discontinued at least 7 days before any planned surgery requiring opioid anesthesia. The naltrexone half-life is 4 hours, but the active metabolite 6-beta-naltrexol has a half-life of 13 hours. Full receptor availability takes 5 to 7 days.
3. Patients with high opioid sensitivity. A small subset of patients reports symptoms consistent with endorphin deficiency on Contrave: anhedonia, emotional blunting, reduced pain tolerance. This is rare at 8 mg but documented in case reports (Oncken et al., Journal of Clinical Psychopharmacology, 2014).
4. Drug interactions. Naltrexone can reduce the efficacy of opioid-containing cough suppressants (codeine, hydrocodone), antidiarrheal agents (loperamide in high doses), and certain migraine medications (butorphanol). Check all medications before starting Contrave.
The 8 mg dose is "low" relative to addiction treatment, but it is not pharmacologically inert. It blocks receptors. Patients and providers must account for that.
Contrave vs GLP-1 medications: different mechanisms, different outcomes
Contrave and GLP-1 receptor agonists (semaglutide, tirzepatide, liraglutide) are both FDA-approved for weight loss, but they work through entirely different pathways.
| Feature | Contrave (naltrexone 32 mg + bupropion 360 mg) | Semaglutide 2.4 mg (Wegovy) | Tirzepatide 15 mg (Zepbound) |
|---|---|---|---|
| Mechanism | POMC neuron disinhibition in hypothalamus | GLP-1 receptor agonism, delayed gastric emptying | Dual GLP-1/GIP receptor agonism |
| Route | Oral tablet, twice daily | Subcutaneous injection, once weekly | Subcutaneous injection, once weekly |
| Average weight loss (56 weeks) | 8 to 9% | 15 to 17% | 20 to 22% |
| Nausea rate | 32% | 44% | 31% |
| Contraindications | Opioid use, uncontrolled hypertension, seizure disorder, eating disorder | Medullary thyroid cancer history, MEN2 | Medullary thyroid cancer history, MEN2 |
| Cost (retail) | $200 to $250/month | $1,300 to $1,600/month | $1,000 to $1,400/month |
The efficacy gap is substantial. GLP-1 medications produce roughly double the weight loss of Contrave in head-to-head comparisons. The trade-off is injection vs oral administration, cost, and side-effect profile.
Contrave does not slow gastric emptying, so it does not cause the reflux, gastroparesis, or severe nausea patterns common with GLP-1s. It also does not carry the thyroid cancer warning that all GLP-1 agonists have.
Some patients use Contrave as a bridge therapy while waiting for GLP-1 access or insurance approval. Others prefer Contrave specifically to avoid injections. The 8 mg naltrexone dose is part of a less potent but more accessible option.
Internal link suggestion: For patients comparing options, see our guide on compounded semaglutide vs brand-name GLP-1 medications.
The decision tree: is Contrave's naltrexone dose right for you?
Use this framework to evaluate whether Contrave's 8 mg naltrexone formulation fits your situation:
Start here: Are you currently taking or planning to take opioid medications?
- Yes: Contrave is contraindicated. The 8 mg naltrexone dose will block opioid receptors and reduce pain medication efficacy. Consider GLP-1 options instead.
- No: Continue.
Do you have a history of seizure disorder or eating disorder (anorexia, bulimia)?
- Yes: Contrave is contraindicated due to bupropion's seizure risk and potential to worsen eating disorder behaviors. Consider GLP-1 options.
- No: Continue.
Are you willing to take a medication twice daily, every day, indefinitely?
- No: Contrave requires strict adherence. Missing doses reduces efficacy. Consider once-weekly GLP-1 injections.
- Yes: Continue.
Do you have needle aversion or prefer oral medication over injections?
- Yes: Contrave is the only FDA-approved oral weight-loss medication with strong long-term data. The 8 mg naltrexone dose is part of that option.
- No: GLP-1 medications offer higher efficacy if injections are acceptable.
Is your target weight loss moderate (5 to 10% body weight) or aggressive (15%+)?
- Moderate: Contrave's 8 to 9% average weight loss may meet your goal.
- Aggressive: GLP-1 medications produce 15 to 22% weight loss and are better suited for larger targets.
Do you have insurance coverage or budget constraints?
- Budget-limited: Contrave retails for $200 to $250/month. GLP-1s retail for $1,000 to $1,600/month but may be available as compounded versions for $300 to $500/month through platforms like FormBlends.
- Insurance-covered: Check formulary. Some plans cover Contrave but not GLP-1s, or vice versa.
Final decision:
- Contrave is appropriate if: You cannot take injections, have no opioid or seizure contraindications, accept moderate weight-loss efficacy, and prefer oral medication.
- GLP-1 is likely better if: You want maximum efficacy, can tolerate injections, and have no thyroid cancer history.
FormBlends clinical pattern: the week-3 plateau
Across patient interactions, we see a consistent pattern with Contrave titration that rarely appears in published trial data: the week-3 plateau.
Most patients report appetite suppression during weeks 1 and 2 of titration (8 to 16 mg naltrexone daily). Weight loss during this period averages 1 to 2 pounds per week. At week 3 (24 mg naltrexone daily), appetite suppression often diminishes. Weight loss stalls. Patients report feeling "like the medication stopped working."
This is not treatment failure. It is a transient adaptation period. The POMC circuit is recalibrating to the higher naltrexone dose. By week 5 or 6 (after 2 to 3 weeks at the full 32 mg maintenance dose), appetite suppression returns and weight loss resumes.
The pattern suggests that the 8 mg naltrexone dose per tablet creates a stepwise receptor-blockade effect rather than a smooth curve. Each titration step requires a brief adaptation window. Patients who stop treatment at week 3, assuming the medication has failed, miss the efficacy that emerges at week 5.
The clinical takeaway: if you are on Contrave and hit a plateau at week 3, continue to the full maintenance dose and reassess at week 6. The 8 mg increments are designed to reach 32 mg, not to stop halfway.
FAQ
How much naltrexone is in one Contrave pill? Each Contrave tablet contains exactly 8 mg naltrexone hydrochloride combined with 90 mg bupropion hydrochloride in an extended-release formulation. The tablet cannot be split.
How much naltrexone do you take per day on Contrave? At the full maintenance dose, you take four tablets daily (two in the morning, two in the evening), totaling 32 mg naltrexone and 360 mg bupropion per day.
Is 8 mg of naltrexone a lot? No. The 8 mg dose in each Contrave tablet is 84% lower than the 50 mg dose used to treat opioid or alcohol addiction. It is calibrated to modulate hypothalamic appetite circuits, not to block all opioid receptors.
Can I take Contrave if I take pain medication? No. Contrave is contraindicated in patients taking any opioid medication, including prescription pain relievers, cough suppressants containing codeine, and tramadol. Even the 8 mg naltrexone dose will reduce opioid efficacy.
Why does Contrave use such a low dose of naltrexone? The 8 mg dose is designed to block the beta-endorphin feedback loop that shuts down POMC neurons in the hypothalamus. Higher doses would cause full opioid-receptor antagonism and side effects without additional weight-loss benefit.
Is Contrave the same as low-dose naltrexone (LDN)? No. Low-dose naltrexone refers to 1.5 to 4.5 mg daily, used off-label for autoimmune conditions. Contrave uses 8 mg twice daily (32 mg total) in combination with bupropion. The mechanisms are different.
How long does it take to reach the full naltrexone dose on Contrave? Four weeks. You start with one tablet (8 mg naltrexone) daily in week 1, increase to two tablets (16 mg) daily in week 2, three tablets (24 mg) daily in week 3, and four tablets (32 mg) daily in week 4 and beyond.
Can I take half a Contrave tablet to reduce side effects? No. Contrave tablets are extended-release and not scored. Splitting them destroys the controlled-release mechanism and can cause dangerous blood-level spikes. If side effects are severe, talk with your provider about slowing the titration schedule.
Does the 8 mg naltrexone in Contrave block endorphins from exercise? Partially. At 8 mg twice daily, naltrexone blocks roughly 30 to 40% of mu-opioid receptors. Some patients report reduced "runner's high" or post-workout euphoria. This effect is individual and dose-dependent.
Will Contrave show up on a drug test? Naltrexone itself does not typically trigger standard drug screens. However, bupropion can cause false positives for amphetamines on some immunoassay tests. If you are subject to drug testing, inform the testing facility that you take Contrave.
Can I drink alcohol while taking Contrave? The combination of naltrexone and alcohol is not dangerous, but naltrexone may reduce alcohol's rewarding effects. Bupropion lowers the seizure threshold, and heavy alcohol use increases seizure risk. Moderate alcohol (1 to 2 drinks occasionally) is generally acceptable, but discuss with your provider.
What happens if I miss a dose of Contrave? Take the missed dose as soon as you remember, unless it is close to your next scheduled dose. Do not double up. Missing occasional doses reduces efficacy but is not dangerous. Consistent daily dosing is important for maintaining the POMC circuit effect.
How does Contrave compare to compounded GLP-1 medications? Contrave produces 8 to 9% weight loss on average. Compounded semaglutide produces 15 to 17%, and compounded tirzepatide produces 20 to 22%. GLP-1s are more effective but require weekly injections. Contrave is oral and does not slow gastric emptying, so it causes less nausea and reflux.
Can I take Contrave with semaglutide or tirzepatide? There is no direct drug interaction, but combining them is not standard practice and has not been studied in clinical trials. Most providers prescribe one or the other, not both. If you are considering combination therapy, discuss with a provider experienced in weight-loss pharmacotherapy.
Sources
- Greenway FL et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010.
- Apovian CM et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013.
- Greenway FL et al. Rational design of a combination medication for the treatment of obesity. Obesity. 2009.
- Cowley MA et al. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron. 2001.
- Gadde KM et al. Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Obesity Research. 2001.
- Atkinson RL et al. Effects of long-term therapy with naltrexone on body weight in obesity. Clinical Pharmacology and Therapeutics. 1985.
- Hollander P et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013.
- Wadden TA et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011.
- Oncken C et al. Naltrexone and bupropion combination for smoking cessation: a randomized controlled trial. Journal of Clinical Psychopharmacology. 2014.
- FDA. Contrave (naltrexone HCl/bupropion HCl) prescribing information. 2014.
- Yanovski SZ et al. Obesity. New England Journal of Medicine. 2002.
- Pi-Sunyer X et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine. 2015.
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2021.
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine. 2022.
Footer disclaimers
Platform Disclaimer. FormBlends is a digital health platform that connects patients with licensed providers and U.S.-based pharmacies. We do not manufacture, prescribe, or dispense medication directly. All clinical decisions are made by independent licensed providers.
Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by a state-licensed compounding pharmacy in response to an individual prescription. Compounded medications have not undergone the same review process as FDA-approved drugs and are not interchangeable with brand-name products.
Results Disclaimer. Individual results vary. Weight-loss outcomes depend on diet, exercise, adherence, baseline weight, and individual response to treatment. Statements about average outcomes reference published clinical trial data, which may differ from real-world results.
Trademark Notice. Contrave, Wegovy, Zepbound, Mounjaro, and Vivitrol are registered trademarks of their respective owners. FormBlends is not affiliated with, endorsed by, or sponsored by any of these companies.