Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies

Psychiatry Res. 2015 Jan 30;225(1-2):31-39. doi: 10.1016/j.psychres.2014.09.005. Epub 2014 Sep 16.


Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the β-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Keywords: Cycloserine; Imagery; Mifepristone; Post-traumatic; Propranolol; Psychophysiology (all MeSH terms); Stress disorders.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Arousal / drug effects
  • Combat Disorders / drug therapy*
  • Combat Disorders / psychology
  • Double-Blind Method
  • Emotions / drug effects
  • Female
  • Heart Rate / drug effects
  • Humans
  • Imagination / drug effects
  • Male
  • Mental Recall / drug effects
  • Middle Aged
  • Mifepristone / therapeutic use*
  • Propranolol / pharmacology
  • Propranolol / therapeutic use*
  • Receptors, Glucocorticoid / drug effects
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Stress Disorders, Post-Traumatic / psychology
  • Veterans / psychology*
  • Young Adult


  • Adrenergic beta-Antagonists
  • Receptors, Glucocorticoid
  • Mifepristone
  • Propranolol