Ibogaine as a Treatment For Alcohol Use Disorder: a Preclinical Investigation

Substance use disorders are a debilitating psychiatric condition which contribute to significant personal, legal and economic problems worldwide. Current treatment options, such as pharmaceutical interventions or behavioural therapy, are not always utilised or effective at reducing symptoms. Ibogaine, a psychedelic compound deriving from root bark of the Tabernanthe iboga plant, has shown potential efficacy in treating symptoms associated with a range of substance use disorders. Ibogaine has also been associated with a range of cardiotoxic side effects and fatalities. Further investigation is necessary to understand both the therapeutic efficacy and side effects associated with ibogaine at different doses. The aim of this thesis is to determine whether a single administration of ibogaine reduces ethanol drinking behaviours, and whether it is associated with any significant cardiovascular side effects, in Sprague Dawley rats.

The Intermittent Two Bottle Access Paradigm (I2BAC) was used to induce ethanol drinking behaviour in the animals over an eight week period. Animals were then administered one of two active doses of ibogaine (20 or 40mg/kg), or saline. Ethanol drinking continued for another five days to investigate any long-term changes. Ibogaine’s side effects were investigated in a separate experiment whereby the rats were surgically implanted with Telemetry devices designed to record the ECG. Recordings occurred at baseline, during saline administration, during ibogaine administration (20 or 40mg/kg), 24 hours post- treatment, 48 hours post-treatment, and 1 week post-treatment. Particular parameters of interest were heart rate and QT interval.

Results of the ethanol drinking experiment provide some evidence of a weak dose- dependent effect of ibogaine on ethanol drinking during its’ acute effects, but do not indicate any significant reductions in ethanol drinking long-term. Results of the side effect experiment indicate a significant effect of ibogaine on both QT interval and heart rate during its acute effects. In light of these results, this thesis also discusses new directions and critical methodological factors for future investigations to consider.