BackgroundStudies have shown that N-methyl-D-aspartate receptor (NMIDA) plays an essential role in postoperative pain. It seems that use of NMDA receptor antagonists such as Dextromethorphan intensifies the analgesic effects of opioids.ObjectivesIn this study, we evaluated the effect of preoperative administration of Dextromethorphan on postoperative pain reduction.Patients and MethodsThis double blind randomized clinical trial was conducted on arthroscopic surgery candidates. Participants were randomly allocated to interventions and assigned to two groups of Dextromethorphan and placebo. In Dextromethorphan group, the patients received 1 mg/kg Dextromethorphan orally the night before the operation. Pain severity based on the visual analog scale (VAS) up to 16 hours postoperation, use of opioids, and the first request for analgesics were recorded postoperatively.ResultsA total of 112 patients in the Dextromethorphan (n = 54) and placebo groups (n = 58) were evaluated. No significant difference was detected between the two groups for age, sex or ASA. The mean amount of opioid consumption was significantly lower in patients who received Dextromethorphan (10.7 ± 5.6 mg) compared to the placebo group (13.1 ± 5.6 mg), (P = 0.03). The mean time until the first opioid request in patients who received Dextromethorphan was longer than that in the placebo group (P = 0.01).ConclusionsThe study results demonstrated that preemptive use of Dextromethorphan reduced postoperative pain and opioid consumption.