Repetitive negative thinking as a risk factor for alcohol use disorders and exploring mechanisms of ketamine as a novel treatment

Abstract

Alcohol use disorder (AUD) is associated with detrimental physical and mental health consequences, as well as societal costs. Repetitive negative thinking (RNT), characterised by recurrent, uncontrollable thoughts on negative themes, is proposed to contribute to AUD by amplifying negative mood which triggers alcohol consumption as a coping mechanism. However, the acute effects of alcohol consumption on RNT have not been empirically examined. Moreover, little is known about the nature of RNT among people with AUD. The first aim of this thesis was to examine the reciprocal relationship between RNT and alcohol consumption. In Chapter 2, I report the acute effects of low or high dose alcohol consumption on state rumination compared to placebo among hazardous and harmful drinkers. These findings indicated that low dose alcohol intake may temporarily terminate ruminative thinking patterns by improving negative mood. In Chapter 3, I explore the subjective experiences of rumination among individuals with AUD. This revealed a self-perpetuating cycle between drinking and rumination, potentially mediated by alcohol focused rumination, negative mood and feelings of shame associated with drinking. Following from this, I examine ketamine combined with psychological therapy as a novel treatment for AUD, and explore potential mechanisms of this treatment. In Chapter 4, I present a systematic review on the evidence base for ketamine treatment for mental health and substance use disorders. This demonstrated that ketamine has the strongest evidence base in depressive disorders, with some evidence of short term decreases in craving and substance use, and increases in abstinence in alcohol and substance use disorders. In Chapter 5, I examine the potential mechanisms of ketamine’s therapeutic effects in AUD, using data from the Ketamine for the Reduction of Alcoholic Relapse (KARE) trial. The results did not support RNT nor the acute subjective effects of ketamine as mediators of treatment effects on abstinence from alcohol. Following from this, in Chapter 6, I present qualitative data from subjective reports of participants from the KARE trial. This indicated a potential role for ketamine induced dissociation and feelings of connectedness in changing their relationship with alcohol. In Chapter 7, I discuss the interpretation and implications of the findings, as well as strengths and limitations of the thesis and suggestions for future research.