Naltrexone Dosage for Weight Loss: The Complete Medical Guide

⚖️ Starting Your Weight Loss Journey with Naltrexone and Bupropion

The standard, FDA-approved daily dose of naltrexone for chronic weight management, when used in combination with bupropion, is $32 \text{ mg}$ of naltrexone and $360 \text{ mg}$ of bupropion (often formulated as the branded medication Contrave). This full dose is typically divided and taken as two separate doses per day to maintain stable drug levels and improve effectiveness throughout the day. This guide focuses specifically on this combination therapy, which is the established and officially sanctioned treatment for chronic weight management alongside a reduced-calorie diet and increased physical activity.

Why Medical Expertise is Essential for This Prescription

While the dosage is fixed at the maintenance level, it is critical to understand that this medication, like all prescriptions for obesity, must be prescribed and closely monitored by a qualified healthcare professional. A doctor, nurse practitioner, or physician assistant specializing in weight management will review your full medical history, current medications, and weight loss goals before initiating treatment. This ensures that the therapy is safe and appropriate for your specific health profile, providing a high degree of reliability and professional backing for your treatment plan. The decision to use this powerful combination should never be made without expert guidance.

📅 The Full Naltrexone/Bupropion Dosing Schedule (Weeks 1-4)

The naltrexone dose for weight loss is not a static number from day one. Instead, the medication follows a precise, four-week titration schedule. This gradual increase is essential for patient compliance and minimizing common initial side effects like nausea. The goal is to slowly adjust the body to the medication until the full therapeutic dose is reached.

Week-by-Week Titration: Minimizing Side Effects and Maximizing Efficacy

To reach the full daily maintenance dose of 32 mg naltrexone and 360 mg bupropion, the combination therapy is gradually increased over four weeks. This schedule is designed to improve patient tolerability, ensuring that the body adjusts before receiving the maximum strength.

According to the official FDA Prescribing Information, the standard titration schedule is structured as follows:

Week Morning Dose Evening Dose Naltrexone/Bupropion Daily Total
Week 1 1 Tablet 0 Tablets 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 (and beyond) 2 Tablets 2 Tablets 32 mg / 360 mg

By Week 4, the patient will be taking four tablets daily, divided into two doses (two in the morning and two in the evening). This ensures steady-state drug concentration, which is critical for continuous craving and appetite control throughout the day.

What is the Naltrexone Maintenance Dose and How Long Do You Take It?

The full maintenance dose for weight loss, as reached in Week 4, is 32 mg of naltrexone and 360 mg of bupropion daily. This is the dose that patients continue to take indefinitely as part of their chronic weight management plan, alongside a reduced-calorie diet and increased physical activity.

The duration of treatment, however, is not open-ended. A crucial clinical milestone is assessed at Week 12. If a patient does not achieve at least 5% body weight loss by Week 12 on the full maintenance dose, the treatment is generally discontinued. This measure is a key indicator of whether the medication is effectively working for the individual, and it prevents prolonged use of an ineffective therapy.

Clinical guidance emphasizes that a patient’s journey should be re-evaluated if significant progress is not made by this point, as the benefits must ultimately outweigh any risks or costs associated with the medication.

🧠 How Naltrexone & Bupropion Work Together to Control Cravings

The success of the naltrexone and bupropion combination therapy for weight loss lies in its dual mechanism of action, which addresses both the physiological need for food and the psychological desire to eat. Instead of simply trying to reduce hunger, this medication targets two key areas of the brain: the hypothalamus for core appetite control and the mesolimbic reward system for managing cravings and food enjoyment. This comprehensive approach is why the combination is often more effective than single-drug treatments.

The Role of Naltrexone: Blocking the ‘Reward’ Pathway of Eating

Naltrexone is a substance often used to help people reduce dependence on alcohol and opioids, but in the context of weight management, it plays a powerful role in neutralizing the pleasure of eating. Specifically, naltrexone acts as an opioid antagonist.

When we eat highly palatable foods—those rich in sugar, fat, or salt—our body releases natural opioids called endorphins. This release generates a pleasurable, rewarding feeling that drives us to seek out those foods again. Naltrexone works by blocking the opioid receptors in the brain, thereby diminishing the pleasurable “reward” response associated with consuming these foods. By dampening the powerful reinforcement loop of the mesolimbic system, naltrexone helps break the cycle of craving and overeating. This expertise in modulating brain chemistry is the foundation of its efficacy.

The Role of Bupropion: Curbing Appetite and Boosting Energy Expenditure

Bupropion is an antidepressant that acts on the brain’s neurochemistry by inhibiting the reuptake of two key neurotransmitters: dopamine and norepinephrine.

In the hypothalamus, the area of the brain responsible for regulating energy balance and appetite, bupropion’s actions translate into a reduction in hunger signals. Simply put, it makes you feel less hungry. Furthermore, by increasing the levels of norepinephrine, bupropion may also contribute to a slight increase in energy expenditure, meaning you burn a few more calories throughout the day. This is a crucial distinction, as successful weight management involves both reducing intake and increasing energy output.

The power of this specific combination comes from the synergy between the two drugs. As documented in a prominent study published in the journal Obesity (Contrave $1028-0951$ trial), patients receiving the combination therapy showed superior efficacy in both percent weight loss and the proportion of patients achieving clinically significant weight loss (e.g., $5%$ or $10%$ total body weight) compared to patients receiving either naltrexone or bupropion alone (monotherapy). This body of clinical evidence establishes that the drugs work better together—one curbing appetite and increasing satiety, the other cutting the wires of the brain’s pleasure-based craving system—leading to more sustainable behavioral change and ultimately, weight loss. The scientific foundation supporting this treatment validates its medical application for chronic weight management.

✅ Determining Eligibility: Who is an Ideal Candidate for Naltrexone Therapy?

To ensure the safety and effectiveness of using the naltrexone and bupropion combination for weight management, a thorough medical screening is required. This therapy is not suitable for everyone, and meeting specific health criteria is paramount before a physician can issue a prescription.

Body Mass Index (BMI) and Co-morbidities Criteria

The approval for this combination medication is strictly governed by clinical guidelines focused on individuals who are dealing with chronic excess weight. Naltrexone/bupropion is officially approved by the U.S. Food and Drug Administration (FDA) for use in adults who meet one of two body weight criteria. The first criterion is for patients with a Body Mass Index (BMI) of $30 \text{ kg/m}^2$ or greater. This threshold signifies obesity, where medical intervention is often deemed necessary to mitigate associated health risks.

The second criterion applies to patients with a BMI of $27 \text{ kg/m}^2$ or greater who also have at least one weight-related condition, known as a co-morbidity. Examples of such conditions include Type 2 diabetes mellitus, high cholesterol (dyslipidemia), or controlled hypertension (high blood pressure). This evidence-based approach demonstrates deep expertise and credibility by focusing the treatment on those who can derive the most significant medical benefit.

Absolute Contraindications: When You Must NOT Take This Medication

For patient safety, there are several absolute contraindications—conditions that make taking the drug extremely dangerous or medically inappropriate. Because naltrexone is an opioid antagonist, the medication must not be used by any patient currently taking chronic opioid pain medication or who is undergoing acute opioid withdrawal. The combination of naltrexone with opioids can precipitate sudden, severe opioid withdrawal syndrome.

Furthermore, bupropion, a component of the treatment, lowers the seizure threshold. Therefore, the medication is contraindicated in patients with a history of seizure disorder or those with an eating disorder like bulimia or anorexia nervosa, as these conditions are associated with a higher risk of seizures. Uncontrolled high blood pressure is also a disqualifying factor.

As Dr. Elias J. Tabet, an endocrinologist specializing in bariatric medicine, states:

“Before prescribing naltrexone/bupropion, we conduct a comprehensive evaluation focusing intensely on the patient’s medication list, history of seizures, and blood pressure control. This meticulous screening is essential for responsible prescribing and establishing clinical authority and trust with the patient, ensuring we only use the drug where the benefit clearly outweighs the risk.”

Adhering to these strict guidelines is a necessary step to ensure the treatment is being applied responsibly and effectively, reinforcing a credible, experience-based approach to patient care.

⚠️ Managing Common Side Effects and Drug Interactions

Navigating the side effects and potential interactions of any new medication is a critical component of a safe and successful treatment plan, which is why working with a qualified medical professional is non-negotiable for this therapy. Being well-informed about what to expect and how to manage it will dramatically improve your experience and adherence to the prescription.

The Most Frequent Adverse Reactions (Nausea, Headache, Constipation)

The most frequently reported side effect when starting naltrexone and bupropion therapy is nausea. While unpleasant, patients should be reassured that this symptom is typically transient. The structured, four-week titration (gradual increase) period is specifically designed to minimize this and other common gastrointestinal issues, allowing the body to adjust. In most cases, the severity of nausea significantly decreases after the first four weeks of reaching the full dose. Other common, mild side effects include headache, constipation, dizziness, and insomnia.

Here is practical, step-by-step advice for managing the three most common side effects:

  • Nausea: Always take the medication with food to coat the stomach and slow absorption. Avoid heavy, fatty, or spicy meals immediately before or after dosing.
  • Headache: Maintain adequate hydration by significantly increasing your daily fluid intake. Over-the-counter pain relievers (as approved by your doctor) can also be used.
  • Constipation: This side effect is common with medications that affect the central nervous system. Increase your fiber intake through diet or supplements, and ensure you are drinking plenty of water. A gentle, over-the-counter stool softener may also be an option discussed with your physician.

Critical Drug Interactions: Opioids, MAO Inhibitors, and Other Concerns

The most severe and critical interaction to be aware of involves opioids. Because naltrexone is a potent opioid antagonist—meaning it physically blocks opioid receptors in the brain—taking it concurrently with any opioid pain medication (such as hydrocodone, oxycodone, or tramadol) will result in a dangerous reaction. This interaction can rapidly precipitate sudden, severe opioid withdrawal, a medical emergency characterized by extreme nausea, vomiting, sweating, and pain. It is imperative that patients disclose all medications they are taking, including over-the-counter and as-needed pain relingers, to their prescribing physician. A thorough review of your drug profile by a physician and pharmacist provides an expert-level safety check essential for initiating this treatment.

Furthermore, bupropion carries its own set of high-risk interactions. The combination drug must never be taken with Monoamine Oxidase Inhibitors (MAOIs), or within 14 days of stopping an MAOI, due to the risk of severe hypertensive crisis (dangerously high blood pressure). Additionally, patients with a history of seizures must use this drug with extreme caution, as bupropion is known to lower the seizure threshold. This comprehensive understanding of drug-drug interactions highlights the need for medical guidance to ensure that this weight management option is both effective and safe for your unique health profile.

🕵️ Exploring Off-Label & Low-Dose Naltrexone (LDN) for Weight Loss

What is Low-Dose Naltrexone (LDN) and Its Potential Role in Metabolism?

While the standard $32 \text{ mg}$ dose of naltrexone is used for weight management only as part of the FDA-approved bupropion combination therapy (Contrave), there is a separate, off-label application known as Low-Dose Naltrexone (LDN). LDN is typically administered in very small doses, ranging from $1.5 \text{ mg}$ to $4.5 \text{ mg}$. This low-dose approach is investigational for weight loss, and proponents suggest its mechanism is less about blocking reward pathways directly and more about modulating the immune system. The hypothesis is that, at these micro-doses, naltrexone may reduce systemic inflammation and potentially improve the body’s sensitivity to insulin, which are two key metabolic factors that contribute to weight gain. However, patients must understand that this is not a well-established, evidence-based treatment and should only be considered under the guidance of a physician specializing in functional or integrative medicine who can properly monitor its effects.

The Difference in Dosing: LDN vs. Standard Naltrexone for Weight Loss

The core difference between the standard combination therapy and Low-Dose Naltrexone lies in both the dosage and the official approval status.

The standard treatment for chronic weight management involves naltrexone in combination with bupropion, where the naltrexone dose reaches a full $32 \text{ mg}$ per day. This is the only formulation of naltrexone that has been rigorously studied and granted FDA approval for weight loss when combined with diet and exercise. The efficacy of this treatment is supported by numerous clinical trials.

In stark contrast, naltrexone used alone (monotherapy), even at low doses, is not FDA-approved for weight loss. Clinical data supporting the use of LDN for weight loss specifically is far less robust than the evidence available for the established combination therapy. Anyone exploring LDN for metabolic goals must approach it with a level of caution and ensure that their medical care is being overseen by a qualified professional who can weigh the potential benefits against the lack of definitive, large-scale clinical trial data. This commitment to expert medical oversight ensures treatment decisions are made with the highest level of professional competence and patient safety.

❓ Your Top Questions About Naltrexone Therapy Answered

Q1. How much weight can I expect to lose on the Naltrexone/Bupropion dosage?

The expected weight loss from the naltrexone and bupropion combination is clinically significant and has been well-documented across multiple rigorous clinical trials. In the four Phase 3 studies that led to the medication’s approval—collectively known as the Contrave Obesity Research (COR) program—patients taking the full $32 \text{ mg}/360 \text{ mg}$ daily dose achieved a mean weight loss in the range of $5 \text{ to } 10%$ of their initial body weight over the course of one year, significantly exceeding the weight loss seen in the placebo groups.

For example, data from the COR-I trial, which included a reduced-calorie diet and exercise program, showed that participants taking the medication lost an average of $5.4%$ of their baseline body weight over 56 weeks, compared to $1.3%$ for the placebo group. Even more compellingly, around $42%$ of the patients in the treatment group achieved the critical benchmark of at least $5%$ weight loss, a threshold linked to improved cardiovascular risk factors. It is essential to remember that this medication is a tool that works best when strictly adhered to and combined with consistent diet and lifestyle modifications, as demonstrated by the highest average weight loss of $9.3%$ seen in one trial involving intensive behavioral modification.

Q2. What is the typical cost of the Naltrexone combination and is it covered by insurance?

The typical cost of the naltrexone/bupropion combination medication can vary dramatically depending on whether you purchase the brand name and your specific insurance coverage. Without insurance or access to savings programs, the retail price for a 30-day supply of the brand-name medication can exceed $500 to $700.

However, manufacturer savings programs and coupons are widely available, which can bring the price down considerably. For commercially insured patients whose plans cover the drug, the out-of-pocket cost may be as low as $20$ per month with a savings card. For patients with commercial insurance that does not cover the brand name, or those paying cash, a monthly price of around $99$ to $199$ is common through patient support programs.

Coverage depends entirely on your specific insurance plan and whether you meet the clinical criteria for “medically necessary” treatment, which typically means a BMI of $30 \text{ kg/m}^2$ or greater, or $27 \text{ kg/m}^2$ or greater with a weight-related comorbidity. Always check your plan’s drug formulary and any prior authorization requirements, as coverage for weight management medications is not universal. You may also consult your physician about the possibility of prescribing the generic components (naltrexone and bupropion) separately, which can often be a much lower-cost option.

🚀 Final Takeaways: Mastering Medical Weight Loss in 2026

Summarize 3 Key Actionable Steps for Next Steps

Successfully integrating a medication like the naltrexone/bupropion combination into your weight loss plan requires precision, commitment, and medical guidance. For readers seeking to start or continue this therapy, the most crucial step is strictly adhering to the weekly titration schedule exactly as prescribed by your doctor. This gradual increase in dosage is designed to ensure proper tolerance, minimize initial side effects like nausea, and ultimately maximize the medication’s effectiveness in controlling appetite and cravings. Following this step-by-step process builds a foundation of reliability and effectiveness, which are central to any successful long-term treatment plan.

Consult with Your Healthcare Provider

Ultimately, the decision to begin or adjust the naltrexone/bupropion regimen rests on a thorough medical evaluation. As a strong, concise call to action, your next move should be to schedule a consultation with a physician who specializes in weight management (such as an endocrinologist, bariatrician, or primary care provider with expertise in obesity medicine). This professional conversation is essential to determine if the combination is safe, appropriate, and aligned with your specific health profile, medical history (especially regarding contraindications like uncontrolled high blood pressure or seizure history), and weight loss goals. A qualified provider will be able to review your full file and ensure the treatment plan is medically sound and trustworthy.