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

Summary

Nitrous oxide (N2O) produces dissociative and psychosis-like effects comparable to those of ketamine in healthy volunteers, making it a practical alternative for modeling these experiences outside clinical settings. Analysis of data from three previous studies found that the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) capture largely non-overlapping subjective experiences during N2O inhalation. A three-factor model of dissociation was confirmed, though a two-factor model may be more parsimonious. Psychosis-like symptoms were represented by two negative and two positive symptom factors. The findings suggest both measures should be used together to comprehensively assess anomalous states from dissociative NMDAR antagonists.

Study at a glance

Abstract

A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) — like ketamine, a dissociative anaesthetic and NMDAR antagonist — has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.