Opioid antagonists for pain

Expert Opin Investig Drugs. 2013 Apr;22(4):517-25. doi: 10.1517/13543784.2013.778973.


Introduction: Opioid receptor antagonists are well known for their ability to attenuate or reverse the effects of opioid agonists. This property has made them useful in mitigating opioid side effects, overdose and abuse. Paradoxically, opioid antagonists have been reported to produce analgesia or enhance analgesia of opioid agonists. The authors review the current state of the clinical use of opioid antagonists as analgesics.

Areas covered: Published clinical trials, case reports and other sources were reviewed to determine the effectiveness and safety of opioid antagonists for use in relieving pain. The results are summarized. Postulated mechanisms for how opioid antagonists might exert an analgesic effect are also briefly summarized.

Expert opinion: Since the comprehensive review by Leavitt in 2009, few new studies on the use of opioid antagonists for pain have been published. The few clinical trials generally consist of small populations. However, there does appear to be a trend of effectiveness of low doses (higher doses antagonize opioid agonist effects). How opioid antagonists can elicit an analgesic effect is still unclear, but a number of possibilities have been suggested. Although the data do not yet support recommendation of widespread application of this off-label use of opioid antagonists, further study appears worthwhile.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Naloxone / therapeutic use
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / therapeutic use*
  • Pain / drug therapy*


  • Narcotic Antagonists
  • Naloxone
  • Naltrexone