Is naltrexone an opioid agonist?

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Last updated: February 14, 2026View editorial policy

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Naltrexone is an opioid antagonist, not an agonist. 1

Mechanism of Action

Naltrexone functions as a pure competitive opioid receptor antagonist that blocks opioid receptors rather than activating them 1. Specifically:

  • Naltrexone competitively binds to mu, kappa, and delta opioid receptors, preventing opioid agonists from binding and producing their effects 2
  • The drug markedly attenuates or completely blocks the subjective effects of intravenously administered opioids through reversible competitive binding 1
  • This antagonist action is analogous to competitive enzyme inhibition, where naltrexone occupies receptor sites without activating them 1

Clinical Implications of Antagonist Properties

The antagonist nature of naltrexone has critical clinical consequences:

  • Naltrexone blocks the euphoric effects of opioids by preventing opioid agonists from activating reward pathways 3
  • In patients physically dependent on opioids, naltrexone will precipitate withdrawal symptoms because it displaces opioid agonists from receptors 1
  • The medication cannot be used in patients requiring opioid analgesics because it blocks pain relief from opioid agonist medications 3
  • 50 mg of naltrexone blocks the pharmacologic effects of 25 mg of intravenously administered heroin for up to 24 hours, demonstrating potent antagonist activity 1

Common Pitfall to Avoid

Do not confuse naltrexone with opioid agonists like methadone or partial agonists like buprenorphine—naltrexone has no agonist properties and produces no opioid-like effects 1. The drug has few, if any, intrinsic actions besides its opioid blocking properties and is not associated with the development of tolerance or dependence 1.

References

Guideline

Opioid Antagonist Pharmacology and Clinical Applications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Naltrexone Treatment for Opioid and Alcohol Dependence

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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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