Concentration-related effects of morphine on cognition and motor control in human subjects

Morphine and other opioid analgesics may interfere with normal cognition and motor function when the drugs are used for long-term treatment of pain. We used individually tailored steady-state drug infusions to identify the nature and extent of cognitive and motor effects of the mu-receptor-selective opioid morphine in healthy volunteers. The tailored infusions allowed evaluation of cognitive and motor effects at three sequential, constant plasma concentrations of morphine in each subject. Compared with functional assessments obtained in a separate saline infusion day, infusions of morphine to plasma concentrations in the usual therapeutic range for analgesia caused significant impairments of some but not all elements of cognitive and motor function. The time needed to encode and process serially presented verbal information increased and the ability to maintain low consistent levels of force decreased during the morphine infusion. We also assessed verbal recall 3 hours after the morphine and saline infusions. Delayed recall of information presented during the morphine infusion was significantly impaired. Our results demonstrate that morphine can interfere with cognitive and motor performance at plasma drug concentrations within the usual therapeutic range.