What is the recommended dose of naltrexone (opioid receptor antagonist) for weight loss?

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Naltrexone Dosing for Weight Loss

The recommended dose of naltrexone for weight loss is 32 mg daily (as 8 mg four times daily), administered as part of the FDA-approved combination therapy with bupropion (Contrave). 1

Dosing Protocol for Naltrexone/Bupropion (Contrave)

Naltrexone is not FDA-approved as a standalone medication for weight loss but is used in combination with bupropion. The recommended dosing schedule is:

  • Week 1: 8/90 mg (naltrexone/bupropion) once daily in the morning
  • Week 2: 8/90 mg twice daily (morning and evening)
  • Week 3: 16/180 mg in the morning, 8/90 mg in the evening
  • Week 4 and beyond: 16/180 mg twice daily (32 mg naltrexone/360 mg bupropion total daily dose) 1

Efficacy and Monitoring

  • Treatment should be discontinued if a patient has not achieved 5% weight loss at 12 weeks on the maximum dosage 1
  • Clinical trials show placebo-subtracted weight loss of 4.7% (range 3.2-5.2%) after 1 year of treatment 2
  • Patients who achieve ≥5% weight loss by week 16 are likely to maintain clinically significant weight loss at 1 year (average 11.7% weight loss) 3

Patient Selection

Naltrexone/bupropion combination is most appropriate for:

  • Patients who describe food cravings or addictive behaviors related to food
  • Patients attempting to quit smoking or reduce alcohol intake
  • Patients with concomitant depression 1

Contraindications

Do not use naltrexone/bupropion in patients with:

  • Uncontrolled hypertension
  • Uncontrolled pain
  • Recent MAOI use
  • History of seizures
  • Conditions that predispose to seizures (anorexia/bulimia nervosa, abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs) 1, 4

Common Side Effects

  • Nausea (most common)
  • Constipation
  • Headache
  • Vomiting
  • Dry mouth
  • Anxiety 1, 5

Serious Adverse Effects

  • Increased blood pressure and heart rate (requires regular monitoring, especially in first 12 weeks)
  • Neuropsychiatric disorders including depression and suicidal ideation
  • Seizures (particularly in predisposed individuals) 4, 5

Important Monitoring Parameters

  • Blood pressure and heart rate should be monitored regularly, especially during the first 12 weeks of treatment
  • Assess weight loss at 12 weeks; discontinue if <5% weight loss achieved
  • Monitor for neuropsychiatric symptoms, particularly in patients with history of depression or anxiety 1, 4

Special Considerations

  • Naltrexone is an opioid receptor antagonist and will block the effects of opioid pain medications
  • The medication is contraindicated in women who are or may become pregnant
  • Women of reproductive age must use reliable contraception 1

Remember that naltrexone as monotherapy is not FDA-approved for weight loss, and the evidence supports its use only in combination with bupropion for this indication.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Antidepressant Combination Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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