To the Editor.— The article by Judd et al, "Naloxone-Induced Behavioral and Physiological Effects in Normal and Manic Subjects" (Archives1980; 37:583-586), states that lethargy is the main behavioral effect of naloxone hydrochloride in manic patients and normal controls. The finding is in agreement with the observation in ex-addicts reported by Jasinski et al 1 and with animal studies. Naloxone also elicits a slight decrease of the average alpha frequency. 2 This shift may be a physiological substrate of the lethargic state. The interesting findings reported by Judd et al raise several questions. What is the mechanism of action of naloxone? The authors hypothesize that "excess and deficiency in opiate receptor activity" may be "responsible for mania and depression respectively." The hypothesis, in addition to its simplicity, has the advantage of fitting the historical evidence of therapeutic efficacy of opioids in depression, as well as the recently reported improvement of