Abstract:
Methadone has been used as a pharmacotherapy for the treatment of opiate dependence since the mid-1960s. It elicits its pharmacodynamic effects by binding to mu opiate receptors as do other opiates. It has been consistently demonstrated that that chronic exposure to opiates can have a negative impact on cognitive function, which might in turn affect normal daily activities and compromise treatment outcomes. Unfortunately, the effects of methadone maintenance treatment (MMT) on cognitive function are poorly described in the scientific literature. Some report a complete absence of deficits while others report a variety of cognitive impairments. The aim of this thesis is to investigate the effects of MMT on the cognitive function of opiate dependent people by conducting three cross-sectional observational experiments with patients undertaking MMT (n=32), opiate-dependent subjects not undertaking MMT (n=17), and healthy volunteers (n=25). The MMT and opiate user groups were found to be well matched on demographic and history drug use variables. The inclusion of a group of people actively using opiates was to assist with differentiating of the effects of MMT from other opiate use on cognitive function. It also helped to control for the possibility of improved cognitive function following prolonged abstinence from illicit opiates and the confounding effects associated with comorbid substance abuse. The first experiment investigated group differences in neuropsychological functioning using a computerised neuropsychological test battery that measured pre-morbid IQ, memory, sensorymotor function, attention, information processing, verbal function, executive function and social cognition. While significant impairments in attention (F (2, 66) =8.79, p=0.001) and executive function (F (2, 64) =5.43, p=0.007) were present in those dependent on illicit opiates, many of these deficits were absent in those undertaking MMT. The second experiment investigated group differences using resting state electroencephalography (EEG) as a measure of neural processing under resting states. The resting EEG spectrum of beta (14.5-30 Hz), alpha (8-13 Hz), theta (4-7.5Hz) and delta (1.5-3.5 Hz) rhythms were recorded. The results showed the resting EEG measures of patients undertaking MMT fell between that of the opiate users and healthy control subjects, and did not differ significantly from that of the healthy controls on most measures. In contrast, those still using illicit opiates exhibited a significant increase in power of the alpha and beta rhythms relative to healthy control subjects. The last experiment examined group differences using event related potentials (ERPs) elicited using a two-tone stimulus auditory oddball paradigm. Compared with healthy control subjects, the MMT and opiate user groups both showed increased P200 amplitude in response to target stimuli. The opiate user group also exhibited a decreased N200 amplitude (F (2, 66) =4.81, p=0.01) and a greater number of task-related errors than healthy control subjects. The P200 represents an initial differentiation of target stimuli from standard stimuli, inhibiting irrelevant information competing for attention, while the N200 is related to stimulus identification and distinction, and reflects the efficiency of pre-conscious sensory processing. Taken together, these findings suggest that cognitive impairment associated with illicit opiate use may be reduced following MMT. The work presented in this thesis provides further support for MMT in the treatment of opiate dependence, suggesting the potential positive effects of substitute treatment on cognitive function. It also demonstrates the benefit of adding neurophysiological measures to cognitive task performance measures for characterising drug effects.