NMDA-receptor blockage to Prevent Trauma Induced Symptomatology

Intrusive memories are common in the aftermath of psychological trauma. The
number of intrusions experienced within days after traumatic events are
associated with acute post-traumatic stress symptoms and predict the
developoment of posttraumatic stress disorder (PTSD). Although there are widely
implemented evidence-based treatments for PTSD, these methods focus on
mitigating stress-related symptoms due to repeated and distressing memory
intrusions over a longer period of time. In contrast, the field so far lacks
interventions to hinder the initial build-up of intrusions.

In this project, pharmacotherapy will be used to target the molecular basis of
memory consolidation in the acute trauma phase to prevent the intrusive aspects
of traumatic memories from forming. An excellent candidate to pharmacologically
manipulate memory consolidation during the acute trauma phase is the
N-methyl-D-aspartate (NMDA) receptor antagonist, esketamine. It is hypothesize
that blocking the NMDA-receptor with a low-dose esketamine will result in less
intrusive memories when administered 1 hour after trauma during memory
consolidation.

The study is a between-subjects design. Participants will receive the study
medication using a nasal spray with either esketamine or the active-comparator
(midazolam) one hour post viewing a car accident in virtual reality (VR).
Participants will experience an incidence of stress induction before this.

Participants receive 1x estketamine (28mg; 14mg per 100mL spray) or 1x the
active-comparator (midazolam; 1.25mg per dosis).

Participants will complete mental health screening questionnaires, provide
saliva samples (3 x sampling), a hair sample (1 sample), 1 blood sample
(7.5ml) for BDNF analysis, blood pressure recordings (3 measurements), and
measures of cognitive functioning. The second lab visit will consist of
exposure to a stress manipulation followed by watching the VR car-accident
scenario and taking the study treatment (esketamine or active-comparator).
Intrusive memories will also be assessed outside the laboratory setting using
the free smartphone app (https://m-path.io) during the subsequent 7 days.
Participants will be invited for an online session one week and one month later
to discuss diary compliance, to fill-out the impact of Event Scale to assess
intrusion, avoidance, and hyperarousal as PTSD related symptoms. These one week
and one month follow-up sessions are also to check how the participant is doing.

The stress manipulation has been shown to be well tolerated (ECP-77-3-01-2009-
2). The VR scenario has been developed for educational purposes for young
drivers by the Leicestershire Fire and Rescue Service. Most important
additional precautions are: determining the absence any mental or physical
disorder and use of any medication. In addition, esketamine and midazolam are
well tolerated when taken 1x intranasal. If there are any side effects, these
are mild and of short-lasting nature.

In case they experience medical complaints, the medical supervisor will be
contacted. If participants feel discomfort after participating, they can
contact an independent clinical psychiatrist (dr. Sjacko Sobczak).