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Adding ultralow-dose oral naltrexone to morphine: a double-blind, randomized clinical trial


Ultralow-dose opioid antagonists can enhance opioid analgesia and prevent tolerance in rodent nociceptive pain assays.


A randomized, double-blind controlled trial is designed to investigate whether the addition of 5 ml ultralow-dose naltrexone (1 μg in a liter of sterile water) to morphine (0.05 mg/kg) changes the total opioid requirement and side effects.


Two hundred and sixty-seven patients (18 to 45 years old) with moderate extremities trauma entered the study, Pain control measurements were evaluated every 15 minutes for the first hour, then every 30 minutes for the second and third hours and finally at the fourth hour. Efficacy was measured by the 11-point numerical pain rating scale. The following side effects were evaluated: sedation, nausea, vomiting and pruritus. We found that opioid requirements did not differ significantly between groups. The morphine + naltrexone group on average required 0.04 mg more morphine during the 4 hours than the morphine group.


The morphine + naltrexone group had a lower incidence of nausea than the morphine + placebo group. However, the incidence of vomiting, pruritus and sedation between the two groups were similar. The combination of ultralow-dose naltrexone and morphine in moderate extremities trauma did not affect opioid requirements, but it decreased the incidence of nausea.


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Correspondence to S Farahmand.

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Farahmand, S., Ahmadi, O. Adding ultralow-dose oral naltrexone to morphine: a double-blind, randomized clinical trial. Crit Care 14, P482 (2010).

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  • Morphine
  • Naltrexone
  • Opioid Analgesia
  • Pain Rating
  • Opioid Antagonist