A rationale for opiate withdrawal symptomatology.

The discovery of opioid peptide transmitters and the delineation of their interactions with the noradrenergic locus ceruleus (LC) has led to our proposing that opiate effects on mood and physiological responses result from the opiate-induced inhibition of the LC. Withdrawal of opiates removes this "tonic" inhibition of the LC and could readily result in a piperoxane-like release from inhibition. The hypothesis that noradrenergic hyperactivity underlies the physiologic and affective changes seen in opiate withdrawal and spontaneous panic seen in man can be readily tested in man by evaluating the efficacy of drugs which inhibit the LC and block piperoxane- and LC-elicited increases in specific behaviors for the treatment of opiate withdrawal and naturally occurring panic-anxiety states in man.