a1 Clinical Psychopharmacology Unit, UCL, London, UK
a2 London School of Hygiene & Tropical Medicine, London, UK
a3 Department of Epidemiology and Public Health, UCL, London, UK
a4 Institute of Cognitive Neuroscience, UCL, London, UK
Background Post-traumatic stress disorder (PTSD) involves maladaptive long-term memory formation which underlies involuntary intrusive thoughts about the trauma. Preventing the development of such maladaptive memory is a key aim in preventing the development of PTSD. We examined whether the N-methyl d-aspartate receptor (NMDAR) antagonist gas nitrous oxide (N2O) could reduce the frequency of intrusive memories by inhibiting NMDAR-dependent memory consolidation in a laboratory analogue of psychological trauma.
Method Participants were randomized to inhale N2O (N = 25) or medical air (N = 25) after viewing a negatively valenced emotional film clip (‘trauma film’). Participants subsequently completed a daily diary assessing frequency of intrusive thoughts relating to the film clip. A week later, participants completed an explicit memory recall task related to the film.
Results Post-encoding N2O sped the reduction in intrusive memory frequency, with a significant reduction by the next day in the N2O group compared to 4 days later in the air group. N2O also interacted with post-film dissociation, producing increased intrusion frequency in those who were highly dissociated at baseline. Sleep length and quality the night after viewing the film did not differ between the groups.
Conclusion N2O speeds the reduction of intrusive analogue trauma memory in a time-dependent manner, consistent with sleep-dependent long-term consolidation disruption. Further research with this drug is warranted to determine its potential to inoculate against enduring effects of psychological trauma; however, caution is also urged in dissociated individuals where N2O may aggravate PTSD-like symptomatology.
(Received October 13 2015)
(Revised January 06 2016)
(Accepted January 20 2016)
(Online publication March 04 2016)