Effect of Morphine on the Electroencephalogram and Other Physiological and Behavioral Parameters

A double-blind, crossover, placebo-controlled study was carried out in 10 healthy male volunteers to investigate the effects of subcutaneously administered single doses of 4 and 8 mg morphine and 2.5 and 5 mg of a new centrally acting analgesic with a benzomorphane structure. After an adaptation session, each subject received all five treatments in a random sequence at intervals of 1 week. Quantified EEG, cardiovascular and behavioral parameters, quantitative respiratory measurements, body temperature, symptom reports, pain threshold estimates, and blood drug assays were used to assess the effects of the drugs. The measurement battery was completed before injection and after 30, 60, 120, 240 and 360 min. In addition, EEG, blood samples and respiratory signals were also taken during/after the first 5, 10, 15, 20 and 25 min. As the new compound did not show any obvious advantages over morphine, only the results with the latter substance are reported here. As the main effects of morphine on the EEG a dose-dependent slowing and monorhythmization of alpha and an increase of the average frequency of fast beta activity were observed. Slow EEG waves tended to decrease. Heart rate and body temperature decreased, whereas there was no discernible effect on blood pressure. Subjects reported feelings of drowsiness, muzziness, lethargy and mental slowness. The pain threshold increased. All these effects had a maximum between min 120 and 240, although the highest blood levels of the parent drug were measured 10-25 min after drug administration. An explanation for this delay might be that the pharmacological effects are due not to free morphine but to one of its metabolites.