The primary outcome is a change from baseline of total ESAS TSDS at day 14. Clinically significant change is determined to be an improvement of the TSDS of ≥6.

The ESAS is a 9 item inventory rated on a 11 point scale anchored at 1 (no problem) to 10 (worst problem). It assesses both physical and psychological symptoms, plus general wellbeing. It has been validated in the assessment of symptoms in cancer patients [13].

Secondary Outcomes include:

1. Patient determined effective dose of CBD formulation, defined as the dose that achieves symptom relief with acceptable side-effects.
2. ESAS TSDS at days 7, 21 and 28.
3. Physical and emotional ESAS scores at each time point.
   • Physical scores will be measured by The Australia modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups- Activities of Daily Living Scale (RUG-ADL). The AKPS is a validated variant of the Karnofsky Performance Status. The Australian version can be applied to both in and outpatients and is sensitive to changes in function over time [14]. The RUG-ADL is an instrument developed for the measurement of nursing dependency. The ADL scale measures patients’ needs for assistance in activities of daily living (eating, bed mobility, transferring and toileting) [17].
4. Individual symptom scores (descriptive analysis only).
5. Oral morphine equivalent (OME), average use at baseline and weekly.
6. SLUMS score baseline and day 14.
   • A person’s capacity to understand the study will be measured using the St Louis University Mental Status Examination. This tool is more sensitive than the Mini Mental Status Examination, and takes school education into account in the score. A score of 23 out of 30 will be considered an appropriate score to assess the ability to complete the study assessments [16].
7. Patient Global Impression of Change (PGIC), days 7 and 14, 21 and 28
   • This is a subjective measure of symptom change done by the patient themselves [18].
8. Clinical Global Impressions (CGI) Scale, days 7 and 14, 21 and 28
   • This is a subjective measure of symptom change done by the investigating clinician [18].
9. DASS-21 score baseline, days 14 and 28
   • DASS-21 is a self-reported 21-item scale, 7 questions per sub-item questionnaire measuring depression, anxiety and stress. The DASS-21 will be used for assessment at baseline (day 0), days 7, 14 and 28 ¹⁹ EORTC score QoL baseline, days 14 and 28 [19, 20].
   • This is a QoL measure found valid for use in a wide variety of cancer populations. To reduce patient burden, we will use the 15 question subset commonly used for the palliative care population.
10. NCI common terminology for adverse events V4.03, day 2, 4, 7, 9, 11, 14, 16, 18, 21, 23, 25 and 28 [21].
    • The NCI CTCAE is a severity grading system for adverse events. Adverse events relate to an unfavourable or unintended sign, symptom or disease temporarily associated with a medical treatment or a procedure which may not be related to the medical treatment or procedure. The CTCAE has a grading of 1 (Mild) to 5 (Death). The known common adverse events associated with cannabinoids are: confusion, somnolence, paranoia, anxiety, mood changes, psychosis, hypertension, tachycardia, hyperhidrosis, nausea, vomiting and abdominal pain [21].

The study will assess adverse events (AE) and serious adverse events (SAE) using the criteria of the NCI, CTCAE V4 [21]. The known common AEs associated with CBD will be specifically addressed at each time point, including dry mouth, diarrhoea, light headedness and drowsiness, nausea, vomiting and abdominal pain). Finally, a detailed concurrent medication list is to be updated and recorded at baseline (day 0), days 7, 14, 21 and 28. This is to include over the counter medications, prescribed medications, complementary and antiemetic medication.