MorphiDex (MS:DM), a 1:1 (weight:weight) ratio of morphine sulfate (MS) to dextromethorphan hydrobromide (DM), is under clinical development for the treatment of moderate to severe pain. The enhancement of MS analgesia by DM is due to a pharmacodynamic interaction, not an effect on MS blood levels or a pharmacokinetic interaction between MS and DM, or their metabolites. Peak blood levels were achieved at approximately 1 hour, similar to MS in solution, resulting in a rapid onset of effect. As the dose was increased, dose-proportionality was linear. Food reduced the peak concentration in blood (Cmax) but not the extent of the absorption. Single-dose, double-blind, placebo-controlled studies in patients suffering from moderate to severe postoperative pain after third-molar oral surgery or orthopedic surgery demonstrated a significantly greater analgesic effect for MS:DM over MS alone with an 8-hour duration of effect. MS:DM is an effective treatment of moderate to severe pain.