A randomized, double-blind controlled trial of medicinal cannabis vs placebo for symptom management in patients with advanced cancer receiving palliative care.

12020 Background: Medicinal cannabis remains very popular amongst cancer patients. In our previous study (JCO 2023; 41(7):1444-1452), cannabidiol (CBD) did not improve symptom management above that provided by standard palliative care alone. This study utilized the same design to test whether the addition of tetrahydrocannabinol(THC) to CBD resulted in improved symptom control. Methods: Patients with advanced cancer and a total symptom distress score (TSDS) of ≥10/90 as measured by the Edmonton Symptom Assessment Scale (ESAS) who were receiving palliative care were randomised to a 10mg/ml THC:10mg/ml CBD combination oil (MC) or matched placebo. The dose was escalated according to tolerance and perceived efficacy from 2.5 to 30mg/day over 14 days and continued at that dose to day 28. The primary outcome was the change in TSDS from baseline at day 14. Secondary outcomes included change in individual symptoms, patient-selected dose, global impression of change, anxiety/depression, opioid use, quality of life and toxicity. Results: Of the 144 randomized from Sept 2019 to July 2023 (72 to MC, 72 to placebo), 56 and 65 participants reached the primary analysis point at 14 days, and 33 and 50 to day 28. The most common cancers were breast, lung and gynecological. Most participants were of reasonable performance status (AKPS 70%) and were taking opioids at baseline. Mean baseline TSDS scores were 37.6/90 (MC) and 36.5/90 (placebo). Mean TSDS scores fell over time with no difference between arms at day 14 (-6.3 (SD 12.3) MC and -6.98 (SD 12.6), p = 0.76) or day 28 (-9.24 (SD 15.3) and 8.42 (SD 13.6), p = 0.8). Adjusted for baseline, there was a significant improvement in pain score from baseline in favor of MC (-1.41 (2.15) vs -0.46 (2.82), p = 0.04) and in overall wellbeing in favor of placebo (-0.48 (2.78) and -1.29 (2.74), p = 0.02) at day 14. The median (range) patient selected dose of oil at day 14 was 1.5ml (0.5-3.0) (equivalent to a dose of 15mgTHC/15mg CBD) and 3.0ml (0.5-3.0) for placebo. Side-effects were generally mild. More participants on MC reported confusion (26/69 and 12/72, p = 0.005), feeling high (21/69 and 10/72, p = 0.02) and an exaggerated sense of well-being (10/69 and 2/72, p = 0.01) as worse than baseline. Those on MC reported an improved global impression of change over time but this lost significance when considering those who exited early. Conclusions: Although showing no advantage over placebo with respect to improving total symptom distress, a 1:1 THC:CBD medicinal cannabis oil resulted in a statistically significant improvement in cancer-related pain at the expense of increased psychomimetic toxicity. Trial registration: ACTRN 12619000037101. Sponsor: Australian Government Medical Research Future Fund. Clinical trial information: ACTRN12619000037101.