The cognitive and psychomotor effects of morphine in healthy subjects: a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo.

Ten healthy subjects (four male) of mean age 31 years (range 25-40) took part in a randomized double-blind four-way crossover study to examine the cognitive and psychomotor effects of repeated oral doses of dextropropoxyphene and morphine. Four treatments were compared: dextropropoxyphene napsylate 100 mg, morphine sulphate 10 mg, lorazepam 0.5 mg and placebo. Four doses of each drug were given at 4-h intervals to each subject on four separate study days at least 1 week apart. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam impaired the speed of responding on all tasks in which speed was recorded (except digit vigilance) and increased subjective ratings of calmness. Morphine had one major effect, which was to increase the accuracy of responding on the choice reaction time task, at every assessment. Morphine produced some sporadic effects in other tests and an increase in subjective calmness. Dextropropoxyphene impaired performance on choice reaction time and picture recognition. These data show that oral morphine may enhance performance in some measures of cognitive function, whereas dextropropoxyphene (in usual therapeutic doses) seems more likely to cause impairment. Neither opioid has substantial effects on cognition and psychomotor function compared with lorazepam.