A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol
Status:
Completed
Trial end date:
2010-08-01
Target enrollment:
Participant gender:
Summary
The consolidation of learning is enhanced by adrenalin and other stress hormones. This memory
enhancing effect is opposed by propranolol. In posttraumatic stress disorder (PTSD), a
psychologically traumatic event may overstimulate stress hormones such as adrenalin, which in
turn overly strengthen consolidation of the memory of the event, leading to an excessively
powerful and persistent memory. Administration of propranolol after a psychologically
traumatic event could reduce subsequent PTSD. Unfortunately, there exists a window of
opportunity for influencing the consolidation of a traumatic event into long-term memory. In
persons who have already developed PTSD, this would have closed months or years earlier.
However, recent developments in animal research suggest that reactivation (retrieval) of a
consolidated memory can return it to a labile state, from which it must be restabilized in
order to persist. This process, which has been termed "reconsolidation," can be reduced in
animals by propranolol.
In a preliminary study performed by the PI and colleagues in Canada, civilian participants
with PTSD described the traumatic event during a script preparation session, which served to
reactivate their traumatic memory. They then received either propranolol or placebo. A week
later, during script-driven imagery of their traumatic events, physiologic responses were
smaller in the participants who had received post-reactivation propranolol compared to
placebo, suggesting that the traumatic memory had been weakened by the propranolol. These
results suggest that that post-reactivation propranolol recapitulates its effects on
consolidation, this time by blocking reconsolidation of the traumatic memory.
Several important questions remain unanswered. First, does propranolol also weaken traumatic
memories in combat-related PTSD? Second, does this weakening effect only occur when the
propranolol is given after combat memory reactivation? If not, this would refute the
reconsolidation hypothesis and suggest that propranolol affects non-specific mechanisms.
Third, how long does the traumatic memory weakening last?
The proposed project will investigate these questions by performing an improved,
double-blind, placebo-controlled study in Iraq and Afghanistan veterans with combat-related
PTSD. Participants will be randomly assigned to one of two groups: post-reactivation
propranolol or non-reactivation propranolol. Participants in the non-reactivation propranolol
group will receive propranolol in the absence of traumatic memory reactivation. Participants
randomized to the post-reactivation propranolol group will receive matching placebo capsules.
Two days later, all participants will return for a script preparation session, at which time
they will describe the details of their traumatic event. Participants randomized to the
post-reactivation propranolol group will then receive propranolol, whereas participants
randomized to the non-reactivation propranolol group will receive placebo. Participants will
then return for psychophysiologic script-driven imagery testing one week and six months
later. We hypothesize that those who receive propranolol after reactivation of their memories
of their traumatic combat event(s) will show significantly smaller psychophysiologic
responses during script-driven imagery testing compared to participants who receive
propranolol in the absence of combat memory reactivation, supporting the inference that
post-reactivation propranolol blocks the reconsolidation of traumatic combat memories.