Codeine-induced memory changes: nature and relationship to opiate system

Learning and recall processes were studied in three experiments with 33 subjects, 1 and 3 h after oral administration of codeine phosphate 25 mg, 50 mg and 100 mg. Recall was measured 3 and 24 h after drug administration. Nine subjects received naloxone i.m. with the 50 mg dose of codeine. Learning and memory were assessed by using associative, serial and concept learning tasks. Flicker fusion frequency was measured to assess the general vigilance level of the subjects. Learning performance in the serial learning task was improved 3 h after administration of codeine 100 mg. Recall in the serial learning task was also improved after codeine 25 mg, but only when the material was learnt after 1 hour and was recalled 24 h after drug intake. To demonstrate the enhanced recall both learning and recall had to take place under the same drug condition. The same test showed a tendency to enhanced recall after codeine 50 mg of material learnt 1 hour after drug intake and recalled 24 h later. This effect was counteracted by naloxone. The data are consistent with the hypothesis that codeine may exert its action via opiate receptors and that this system participates in memory functions.