An Investigation of the Acute and Chronic Effects of Ketamine on Cognition

The work presented in this thesis aimed to investigate the consequences and causes of ketamine abuse and compare them with the acute effects of the drug. Seven experimental chapters report the findings of a total of 9 studies: 5 with ketamine users, 3 administering ketamine to healthy volunteers and 1 with psychosis-prone individuals. Acute studies with volunteers demonstrated ketamine-induced impairments to item recognition, source memory, controlled semantic processing, working memory and procedural learning. There was also a suggestion of a disruption in self-monitoring but perceptual priming and executive functioning were largely preserved. Ketamine was subjectively reinforcing in healthy volunteers. Suggested chronic effects of ketamine in drug users included deficits in source memory and controlled semantic processing indicative of a degraded semantic store. Following substantial reduction in ketamine use, semantic function appeared to recover whilst episodic and attentional impairments appeared persistent. Overall, this thesis suggested that ketamine, both acutely and chronically, produces selective cognitive impairments, particularly to those functions that require integration of contextual information. The implications of this thesis are drawn out for an acute versus ‘chronic’ model of psychosis. Chronic deficits in ketamine users may reflect neurological changes associated with repeated NMDAreceptor antagonism and hence may be more similar to changes observed in the later stages of schizophrenia, whereas acute ketamine may better model the acute phase. Persisting cognitive impairments are of concern in light of the burgeoning population of ketamine users.