Volavka and Jacquet raise some issues of interest. It is true that at the inception of our studies the working hypothesis was that an excess or deficiency in opiate receptor activity might be responsible for mania and depression, respectively. This hypothesis was helpful in the beginning, but it has proved to be much too simplistic to effectively explain the potential role the opioid peptides may play in the pathophysiology of affective disorder. Therefore, we have abandoned this hypothesis.
As Volavka and Jacquet point out, were the original hypothesis to be correct, naloxone hydrochloride should accentuate depression and exogenous opiates or opioids should exacerbate mania. We have preliminary data that have bearing on this issue. We have studied eight acutely manic patients who were administered 10 mg of methadone hydrochloride intramuscularly in a crossover, double-blind study. Systematic observations of the patients' behavior before and after placebo or methadone administration revealed a