Chronic ketamine use and psychotic symptomatology

This thesis examines the effects of chronic use of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, on subjective experience and cognition. It is important to explore the chronic effects of ketamine as the number of individuals using the drug recreationally is increasing both in the UK and worldwide. There is a paucity of research exploring the chronic effects of ketamine. Many studies have shown that acutely ketamine induces psychotic-like symptomatology and specific cognitive dysfunction in healthy, drug-naive volunteers. For this reason, a ketamine model of the psychoses has been proposed. However the few studies of the effects of chronic ketamine have provided mixed findings. Part 1 of the thesis comprises a literature review, which investigates the psychotomimetic effects of ketamine, through the synthesis of current research findings, to determine whether ketamine is a useful model of the symptomatology characteristic of the psychoses. It presents an overview of ketamine and its association with the psychoses, before providing a detailed account of the functional psychoses and drug models of the psychoses (namely the dopamine hypothesis, the serotonin hypothesis and the glutamate hypothesis). The review then synthesises the acute and chronic ketamine studies to date, highlighting which states appear to be best modelled (i.e. the pre-psychotic, acute or chronic state experienced by individuals with idiopathic psychoses). Finally, the review briefly considers the treatment implications of the ketamine model of psychoses, and the risk chronic ketamine use poses to users in terms of developing fully-manifest psychotic symptomatology. In Part 2, an investigation of the chronic effects of ketamine on subjective experiences and cognitive functioning is reported, in order to determine whether chronic ketamine models symptomatology associated with the pre-psychotic state of idiopathic psychoses (where the term idiopathic refers to psychotic symptomatology of unknown aetiology, i.e. that which occurs in the majority of the general population and is not drug-induced). This investigation was part of a joint project conducted with 2 other trainees to investigate the chronic effects of ketamine, cannabis and cocaine on subjective experiences and cognitive functioning (See Appendix 1 for details of the contribution made by each trainee). The empirical paper reports a between subjects study which compared 21 frequent ketamine users (who used ketamine daily), 20 infrequent ketamine users (who used ketamine a maximum of once or twice a week) and 20 controls (who reported no illicit drug use). On a clinical index of symptomatology (SPI-A), a 'frequency' effect was observed: frequent ketamine users were found to be higher in psychotic-like symptomatology (i.e. basic symptoms) than infrequent users, who in turn were found to be higher in symptomatology than controls. Both groups of ketamine users were also found to be higher in psychosis proneness on a general population index of psychotic-like markers (OLIFE) compared with controls. Furthermore, both groups of ketamine users demonstrated impaired episodic memory and working memory compared to controls. Group differences were found in executive functioning. Part 3 comprises a critical appraisal of the research. It includes reflections on my experience of the research process and conducting research with the ketamine using population, as well as reflections on clinically relevant observations.