2026 ECNP Congress

PS03-3260

Administration of 50%-nitrous oxide during memory encoding increases intrusive memory detachment and impairs voluntary recall in healthy volunteers

Ursule Taujanskaite — S.K. Kamboj · University College London, Clinical Psychopharmacology Unit, London, United Kingdom

2026 ECNP Congress

Background

Post-traumatic stress disorder (PTSD) can be conceptualised as a disorder of memory. Intrusive memories are a central symptom in PTSD, contributing to the maintenance of the disorder, and represent an important target for intervention. Nitrous oxide (N2O), an N-methyl-D-aspartate (NMDA) receptor antagonist, has previously been shown to accelerate the decay of intrusive memories when administered following an experimental analogue of psychological trauma, consistent with a consolidation-disruption mechanism [1]. However, it remains unclear whether N2O exerts similar effects when administered during memory encoding. N2O is known to elicit pronounced dissociative states [2], and peri-traumatic dissociation has previously been shown to be significant predictor of later PTSD symptom severity [3]. The present study therefore investigated the effects of N2O administered during encoding on memory expression in healthy volunteers, and whether these effects were dependent on subjective dissociation produced by N2O.

Methods

The current study employed the trauma film paradigm as a model of psychological trauma [4]. Healthy volunteers (N = 120) were randomised to inhale either N2O (N = 80) or medical air (N = 40) for 40 minutes, during which they watched the trauma film. Dissociation was measured via the Clinician-Administered Dissociative States Scale (CADSS) at pre-, peri- and post-inhalation, alongside other measures of subjective state (e.g., sedation, stimulation). Following the experimental session, participants completed a seven-day diary recording the frequency, content and features of intrusive memories. Voluntary recall of the film was assessed on day 7 using a cued recall task.

Results

Compared to the control group, participants in the N2O condition reported significantly greater detachment associated with intrusive memories at follow-up, alongside a trend-level increase in intrusion frequency. In addition, N2O administration was associated with significantly impaired voluntary recall of the film content on day 7. Mediation analyses indicated that peri-inhalation dissociation significantly mediated both increased detachment of intrusive memories and reduced voluntary recall performance.

Discussion

In contrast to previous findings of post-encoding N2O reducing intrusive memory persistence, N2O administration during memory encoding did not attenuate intrusions, and instead appeared to worsen aspects of their presentation, particularly subjective detachment, while at the same time producing impaired voluntary recall. The effects of N2O on both voluntary and involuntary memory were mediated by peri-inhalation dissociative state. The current findings are consistent with the Dual Representation Theory account of PTSD [5] and suggest that N2O-induced dissociation during encoding may have biased the memory encoding towards the processing of sensory-perceptual details at the expense of higher-order, contextual information. This imbalance may underlie the observed pattern of greater intrusive memory detachment and reduced accessibility for voluntary recall. Overall, these results highlight the importance of both the timing of N2O administration and individual sensitivity to its subjective effects, in determining its impact on trauma memory formation and expression.

References

  1. Das, R. K., Tamman, A., Nikolova, V., Freeman, T. P., Bisby, J. A., Lazzarino, A. I., & Kamboj, S. K. (2016). Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma. Psychological medicine, 46(8), 1749-1759.
  2. Piazza, G. G., Iskandar, G., Hennessy, V., Zhao, H., Walsh, K., McDonnell, J., … & Kamboj, S. K. (2022). Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide (‘laughing gas’)-induced anomalous states. Psychopharmacology, 239(7), 2317-2329.
  3. Briere, J., Scott, C., & Weathers, F. (2005). Peritraumatic and persistent dissociation in the presumed etiology of PTSD. American Journal of Psychiatry, 162(12), 2295-2301.
  4. James, E. L., Lau-Zhu, A., Clark, I. A., Visser, R. M., Hagenaars, M. A., & Holmes, E. A. (2016). The trauma film paradigm as an experimental psychopathology model of psychological trauma: Intrusive memories and beyond. Clinical psychology review, 47, 106-142.
  5. Brewin, C. R., Gregory, J. D., Lipton, M., & Burgess, N. (2010). Intrusive images in psychological disorders: characteristics, neural mechanisms, and treatment implications. Psychological review, 117(1), 210.