Degree Name

Master of Research


School of Medicine


Impairment in cognitive functioning is a core component of opioid dependence due to its importance in the course of addiction and its role in treatment, but the effect of opioid use on cognition in individuals undergoing early stages of treatment is under examined, particularly in the Australian population. Although existing pharmacological options have demonstrated some efficacy in treating opioid dependence, they are limited in their ability to treat the cognitive dysfunction present in opioid dependent individuals. Hence, there is a need for novel treatment options that address these limitations. The commensal gut microbiota can engage in bidirectional communication with the brain and thus influence brain function, including cognition. Dysbiosis of the microbiota has been reported in several areas of addiction and concomitant cognitive impairment, and may serve as a target for potential future novel treatments. The effect of opioid use on the gut microbiota is inconclusive, however. The present thesis aimed to: a) investigate cognition in individuals with a history of chronic opioid use during the early stages of rehabilitation treatment in an Australian setting; b) examine the effect of opioid use on the gut microbiota, and; c) outline the functional potential of the gut microbiota in opioid use and how it may relate to key signalling pathways of the microbiota-gut-brain axis. In Chapter 2, Australian participants at early stages of community-based rehabilitative treatment (including treatment with methadone or buprenorphinenaloxone, BNX) underwent neurocognitive testing. Results demonstrated impaired cognitive functioning compared to the general population, but no significant differences between performance in BNX compared to methadone-treated participants. BNX treatment was associated with a longer length of stay, which could indicate greater treatment adherence. The potential influence of treatment and non-treatment related parameters were also examined. Treatment related factors (e.g., time since last dose, life-time length of treatment) had a significant relationship with cognitive performance in BNX-treated participants, but not methadone treated participants. Neurocognitive performance was also significantly influenced by non-treatment related demographics factors, such as age and BMI. Together, these findings demonstrate cognitive impairment in people undergoing residential rehabilitation for opioid addiction and highlight treatment and demographics parameters that could potentially influence cognitive outcomes and should be considered in future studies.

In Chapter 3, a systematic literature review was conducted to investigate the effect of opioids on the gut microbiota. Results demonstrated that opioid use resulted in dysbiosis of the gut microbiota, and identified specific microbes that were repeatedly dysbiotic across clinical and preclinical studies for the first time. Opioid use also resulted in alterations to key signalling pathways of the microbiota-gut-brain axis, suggesting the potential for opioid induced dysbiosis of the gut microbiota to influence cognition. These results may have significant implications for future research aiming to better understand the pathology of opioid dependence, and may inform the development of future novel treatments that improve the lives of people with opioid dependence.



Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.