Physostigmine reduces the plasma cortisol response to methylphenidate in normal subjects.

Six healthy male subjects were studied to determine whether the reduced plasma cortisol response to methylphenidate observed in depressed patients could be reproduced in normal subjects by pretreatment with physostigmine. Indeed, physostigmine was found to mimic this effect. The finding raises the possibility that increased cholinergic rather than decreased adrenergic activity could explain the blunted cortisol response to stimulants reported in depressed patients. Physostigmine also enhanced the growth hormone rise and prolactin decline, and limited the increase in heart rate following methylphenidate administration.