Table 1 Table of all primary and secondary outcome measures included in study

Basic

Demographics

7 Questions: basic demographics including: age, gender, sexuality, Aboriginal and Torres Strait Islander background, education level, employment status, relationship status and living situation. Categorical data, excluding age which is discrete numeric

Research Interview: Week 1 (baseline) Day 1

Cannabis Use

Modified Time Line Follow Back (TLFB) [64]

Cannabis free days, self-reported using a modified timeline follow back (TLFB). Week 1 and 25 interviews will ask about cannabis use in the preceding 4-weeks; week 4, 7, 10 and 13 interviews will ask about the preceding 3-weeks. Bounded count; number of days abstinence (out of 84)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Diagnostic & Statistical Manual of Mental Disorders (DSM-V) [65]

Severity of Cannabis Use Disorder in the prior 12-weeks using the modified (DSM-5 criteria) MINI scale. Number of DSM-5 CUD criteria met out of 11 (Mild CUD: 2–3; Moderate CUD: 4–5; Severe CUD: 6 +)

Bounded count, number of DSM-5 CUD criteria met (out of 11)

Research Interview/ Clinical review: Week 1 (baseline), 13 and 25

Cannabis Use History

7 semi-structured questions exploring: history and frequency of cannabis use and any previous attempts at reducing cannabis use. Continuous

Research Interview/ Clinical review: Week 1 (baseline)

The Substance Use Goals Questionnaire (SUG)

Bespoke scale developed by addiction medicine specialists involved in the CBD-CUD Study. Participants goal towards their cannabis use. Measured using a self-reported substance use goals questionnaire: 2 items with 5 response categories. 5-level ordinal

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Rates of Abstinence

The proportion of participants who achieve pre-identified levels of abstinence from cannabis use (weekly rates), and a 50% reduction in cannabis use days compared to the pre-treatment 4-week period. Binary categorical (non-abstinent vs abstinent)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Cannabis Withdrawal Scale (CWS) [51]

19 items on a 10-point Likert Scale, with 0 = Not at all to 10 = Extremely. The CWS is used as a diagnostic instrument to assess severity of cannabis withdrawal symptoms. Self-report over the last 24 h in 8 domains; irritability, depression, anxiety, cannabis cravings, physical symptoms, sleep difficulty, restlessness and appetite. Continuous (average item score as a 0–10 range, converted to a z-score)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Marijuana Craving Questionnaire – short form (MCQ) [66]

12 items on a 7-point Likert scale, with 1 = strongly disagree to 7 = strongly agree. The MCQ is a self-report instrument that assesses marijuana craving along 4 dimensions; compulsivity, emotionality, expectancy and purposefulness. Continuous (average item score as a 0–10 range, converted to a z-score)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Marijuana Problems Scale (MPS) [67, 68]

19-item MPS measuring potential negative effects of marijuana on social relationships, self-esteem, motivation and productivity, work and finances, physical health, memory impairment and legal problems on a 3-point Likert scale, with 0 = no problem, 1 = minor problem or 2 = serious problem. Continuous (total count of problems (0–19) or as a summed total of severity rating (0–38)

Research Interview: Week 1 (baseline), 13 and 25

Urine Drug Screen

Urinary Drug Screen (UDS) collected to analyse for quantitative creatinine adjusted THC-COOH and CBD-COOH. Continuous (ng/ MoL)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Other Substance Use

Australian Treatment Outcomes Profile (ATOP) [69]

3-Part Questionnaire:

1. Substance use; items refer to substance use over the last 4-weeks, in particular: alcohol, amphetamines, benzodiazepines, heroin, other opioids, cocaine, other substances and tobacco

2. Injecting risk behaviour; 2-items exploring injecting behaviour in the last 4-weeks

3. Health and Well-being; 11-items investigating the participants’ accommodation arrangements, psychological and physical health and quality of life

Bounded count (days of use/ abstinence in previous 28-days)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Fagerstom Test for Nicotine Dependence (FTND) [70]

6-item questionnaire that measures nicotine dependency, with a total available score of 10. Continuous (range 0–10, converted to z-score)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Mental and Physical Health

Psychotomimetic States Inventory (PSIa) [71]

48-item questionnaire with subscales in delusional thinking, perceptual distortions cognitive disorganisation, anhedonia, mania, and paranoia. Continuous (range 0–48, total and subscale scores each converted to z-scores)

Research Interview: Week 1 (baseline), 7, 13, and 25

PCL-5 for Post Traumatic Stress Disorder (PTSD) [72]

20-item self-report measure of the 20 DSM-5 symptoms of PTSD. The four domains consist of: Re-experiencing, Avoidance, Negative alteration in cognition and mood and Hyper-arousal. Continuous (range 0–80)

Research Interview: Week 1 (baseline), 13 and 25

Patient Reported Outcomes Measurement Information System (PROMIS-29) v2.1 [58]

29-item self-report measure assessing the past 7-days. The seven domains include: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference and intensity. A 5-point Likert scale (range 1–5) to measure symptom severity or frequency. Continuous (total and subscale scores converted to a z-scores)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Social/ Other

Treatment Satisfaction Questionnaire for Medication (TSQM) [73]

14-item questionnaire across four domains focusing on drug effectiveness, side effects, convenience and global satisfaction of the medication. Continuous (range 0–100)

Research Interview: Week 4, 7, 10, 13 and 25

Drug Effects Questionnaire-5 (DEQ-5) [74]

5-item questionnaire assessing consumer ratings of drug effects. Continuous (range 0–7)

Research Interview: Week 4, 7, 10, 13 and 25

Testing the Blind

2-questions exploring the participants’ subjective opinion of study drug allocation. Binary categorical (placebo vs CBD) and continuous (% confidence)

Research Interview: Week 1 (baseline), 4, 7, 10, 13 and 25

Safety Adverse Events

Adverse events assessed with study clinician to assess for any side effects of study drug. Unbounded count

Research Interview: Week 1 (baseline), 4, 7, 10 and 13

Treatment Retention

Calculated from treatment records and participant withdrawal/ completion form. Discrete numeric (week of dropout)

Clinical review: week 13

Modified Everyday Discrimination Scale (m-EDS) [75]

10-item instruments based on the Discrimination/ Racism in Everyday Life and 6-item instrument based on Discrimination/ Racism in Healthcare adapted to a diverse Aboriginal and Torres Strait Islander context. Participants are asked to report the extent to which they experience discrimination in different settings, with the response options of ‘not at all’, ‘a little bit, ‘a fair bit’ and ‘a lot’. Continuous

Research Interview: Week 1 (baseline)

Qualitative research interviews

Qualitative research interviews will be conducted with Indigenous Australian participants who consent to participate. Qualitative methods will collect data on how participants’ experience of racial discrimination, identification with culture and community, and how their social and cultural networks (peers, family and local community) impact on attempts to change their cannabis use, as well as how participants perceive their cannabis use and identify their treatment goals and how participants engage with the study treatment procedures (medication, counselling and the role of Aboriginal Health Workers at study sites

1 interview during weeks 7–13 (flexible)

Cognitive Assessment

National Adult Reading Test 17-word version (NART17) [76]

The NART is a prevalent tool used in clinical scenarios to predict an individual’s prior level of intelligence, often crucial in neuropsychological studies and practices. The NART-17 consists of 17 written words in British English which all have irregular spellings. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline)

Rey Auditory Verbal Learning Task (RAVLT) [77]

Test of verbal learning and memory. Retention of a 15-item word list presented on 5 occasions. Number of words recalled on each presentation, following presentation of a novel list of 15 words; and then after brief and long delays recorded. Recognition of target stimuli also assessed. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline) and 13

Eriksen Arrow Flankers (with no-go) [78]

Speed of response to target stimuli flanked with either neutral, congruent or incongruent stimuli (24 each). Random 10% (n = 8) trials require with-holding of response (no-go). Reaction time: errors and false alarms recorded. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline) and 13

N-Back [79]

N-back is a continuous performance task to measure verbal working memory and is dependent on the integration of the frontal and temporal regions, two areas particularly affected by THC. Participants are instructed to monitor a series of stimuli and to respond whenever a stimulus is presented that is the same as the one presented n trials previously. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline) and 13

Digit Span Task [80]

Task evaluates working memory. The test consists of two-parts: (1) ‘Digits Forward’, requires the participant to repeat sequences of number in the order given; (2) ‘Digits Backward’, requires participant to recite the numbers in reverse order. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline) and 13

Trail Making Test (TMT) [81]

The TMT is a tool used to gauge an individual’s attention, processing speed and cognitive flexibility. It has two parts, in which the participant is instructed to connect a set of 25 dots as quickly as possible while maintaining accuracy. Continuous (scales converted to a z-score)

Research Interview: Week 1 (baseline) and 13