A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder

Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and five or more drinks in a day for men). This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels

Liver Function will be assessed through blood sample at baseline. We will measurement levels of enzyme gamma-glutamyl transferase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT).

Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels

Examine the cost-efficacy between NAC and placebo from both health sector and societal perspectives. Measured by Disability-Adjusted Life Years (DALYs)

As measured by the Alcohol Craving Experience Questionnaire (ACEQ). Higher scores indicate more severe craving.

Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels

Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.

Measured by cumulative scores on the DASS-21 Anxiety Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more anxiety.

Measured by cumulative scores on the DASS-21 Depression Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates greater depression.

Measured by cumulative scores on the DASS-21 Stress Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more stress.

As measured by the ISI (Insomnia Severity Index). This Index has a minimum score of 0 and a maximum score of 28. The higher the score indicates more severe insomnia.

To examine the adverse consequences a participant has experienced in their lifetime due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured using the Drinker Inventory of Consequences Lifetime Edition (DrInC-2L). Higher scores indicate more consequences.

To examine the adverse consequences a participant has experienced in the last 3 months due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured using the Drinker Inventory of Consequences Recent Edition (DrInC-2R). Higher scores indicate more consequences.

To examine the change in adverse consequences a participant has experienced across the trial due to alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. This is measured by comparing the Drinker Inventory of Consequences Recent Edition (DrInC-2R) and the Drinker Inventory of Consequences Lifetime Edition (DrInC-2L). Higher scores indicate more consequences.

Daily texts will be sent out to participants querying the amount of alcohol they have consumed. Participant responses to this will be recorded. This will be managed through SEMA software.

Measured by the Fagerstrom Test for Nicotine Dependence (FTND). This test has a minimum score of 0 and a maximum score of 10. Higher scores indicate a more intense physical dependence on nicotine.

As measured by the Suicidal Ideation Attributes Scale (SIDAS). This scale has a minimum score of 0 and a maximum score of 50. Higher scores indicate more severe suicidal thoughts.

As measured by the Caravan Spotter task of the Cognitive Impulsivity Suite (CIS). This measures information gathering through a perceptual decision making task whereby the target is initially ambiguous but progressively becomes clearer.

As measured by the Bounty Hunter task of the Cognitive Impulsivity Suite (CIS). This measures attentional control using a Go/No Go task.

As measured by the Prospectors Gamble task of the Cognitive Impulsivity Suite (CIS). This involves a probabilistic reverse learning task to measure monitoring of feedback.

As measured by the Brief Irritability Test (BITe). This test has a minimum score of 0 and a maximum score of 30. Higher scores indicate greater irritability.

To assess an individuals' health based on the previous 7 days of physical activity. This is measured by the International Physical Activity Questionnaire (IPAQ-Long). We are interested in whether across treatment, answers to this questionnaire will change.

To assess whether treatment can change quality of life as measured by the short form Health Survey (SF-36). This survey has 36 items that measure 8 domains of health, including: physical functioning, physical role limitations, bodily pain, general health perceptions, energy/vitality, social functioning, emotional role limitations and mental health. The scores are transformed to range from 0 (worst possible health) to 100 (best possible health).

As measured by the EQ-5D-5L. This instrument measures 5 different domains of life including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is assessed by one question. This instrument has a minimum score of 0 (worst possible health) and a maximum score of 1 (best possible health).

As measured by the Stroop Colour Word Test. This test measures ability to inhibit prepotent responses and processing speed. This is assessed through the time it takes for an individual to appropriately select an incongruent response. For example, selecting "black" for the word "black" that is coloured in "green". Higher scores indicate worse performance.

As measured by the Trail Making Task (TMT). This test measures the ability to an individual to process visual stimuli, as measured in time. In the TMT Part A, individuals are instructed to draw a line between numbers, 1-2-3-4-5. Higher time indicates slower processing speed. In the TMT Part B individuals are instructed to switch between drawing lines between numbers and letters, for example 1-A-2-B-3-C. Higher time indicates worse processing speed and switching ability.

As measured by the PCL-5. This self-report questionnaire lists 20-items that assess DSM-5 PTSD criteria. A higher score indicates greater severity

As measured by the Brief Health Services Use Questionnaire. This questionnaire assesses Health Service Use across the last 3 months.

Daily texts will be sent out to participants querying the hangover symptoms they are experiencing, if any. Participant responses to this will be recorded. This will be managed through SEMA software.

We will use blood samples collected at baseline to measure redox markers (GPxBC, GSHBC). At the end of treatment we will see whether these markers are predictive of treatment response

We will use blood samples collected at baseline and wk 12 to measure changes in redox markers (GPxBC, GSHBC)