Medicinal cannabis for symptom control in advanced cancer: a double-blind, placebo-controlled, randomised clinical trial of 1:1 tetrahydrocannabinol and cannabidiol.

Purpose: Patients with cancer commonly access cannabis hoping to relieve their symptoms. This study assessed whether a 1:1 10 mg/ml THC:CBD combination oil could improve total symptom burden in patients with advanced cancer over that provided by palliative care alone. Methods: Participants were randomised to medicinal cannabis (MC) or placebo oil; dose escalated over 14 days according to tolerance and efficacy and continued to day 28. Symptoms assessed using the Edmonton Symptom Assessment Scale (ESAS) were summated to give a total symptom distress score (TSDS). The primary outcome measure was the change from baseline in TSDS at day 14. Secondary outcomes included individual symptom scores, opioid use, participant-selected dose, QoL, psychological symptoms, global impression of change (GIC), and adverse effects. Results: The pre-planned sample size of 120 at day 14 was reached following the randomisation of 144 patients. Mean (SD) TSDS improved over time in both arms (- 6.30 (12.3) MC, - 6.98 (12.56) placebo, p = 0.76) to day 14 with no difference between arms. A statistically significant improvement in ESAS pain scores in the MC arm (mean (SD) - 1.42 (2.15) MC and - 0.46 (2.83) placebo, p = 0.04) was at the expense of greater psychomimetic toxicity. Improvement in general well-being was greater for the placebo. GIC and the pain component of QoL both favoured Mc. Conclusions: Patients can be informed that a 1:1 THC:CBD combination cannabis oil was no better than palliative care alone in palliating symptoms in patients with advanced cancer. A small benefit in pain control was associated with greater toxicity. Trial Registration: Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12619000037101, 14/01/2019.