A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Propranolol; Placebo
Intervention description: 0.67 mg/kg short-acting propranolol combined with 1 mg/kg long-acting propranolol; Placebo (matching propranolol) short-acting and long-acting capsules
Intervention MeSH terms: Propranolol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: stress disorders; post-traumatic; memory; propranolol; psychophysiology

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.
    

Eligibility criteria:

        Inclusion Criteria: Afghanistan and Iraq War veterans who have been diagnosed as having
        combat-related PTSD

        Exclusion Criteria:

          1. PTSD Checklist (PCL) score (administered at the referring site) ≤ 50;

          2. Current, co-existing PTSD of non-combat origin

          3. Resting systolic blood pressure <100 mm Hg

          4. Medical condition that contraindicates the administration of propranolol

          5. Previous adverse reaction to, or non-compliance with, a β-adrenergic blocker

          6. Presence of drugs of abuse

          7. Pregnancy

          8. Contraindicating psychiatric condition

          9. Initiation of, or change in, psychotropic medication within the two months prior to
             recruitment

         10. Current use of medication that may involve potentially dangerous interactions with
             propranolol

         11. Inability to understand the study's procedures, risks, and side effects, or to
             otherwise give informed consent for participation

         12. Does not understand English