Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD).

Purpose: To determine whether cannabidiol (CBD) oil can improve symptom distress in patients with advanced cancer receiving palliative care. Methods: Participants were adults with advanced cancer and symptom distress (Edmonton Symptom Assessment Scale [ESAS] total score of >/= 10/90) who received titrated CBD oil 100 mg/mL, 0.5 mL once daily to 2 mL three times a day, or matched placebo for 28 days. The primary outcome was ESAS total symptom distress score (TSDS) at day 14. Response was defined as a decrease in TSDS by >/= 6 at day 14. Secondary outcomes were ESAS TSDS over time, individual symptom scores, patient-determined effective dose, opioid use, Global Impression of Change, depression, anxiety, quality of life, and adverse events. Results: Of the 144 patients randomly assigned, the planned sample size of 58 participants on CBD and 63 on placebo reached the primary analysis point (day 14). The unadjusted change in TSDS from baseline to day 14 was -6.2 (standard deviation, 14.5) for placebo and -3.0 (standard deviation, 15.2) for CBD with no significant difference between arms (P = .24). Similarly, there was no detected difference in proportion of responders (placebo: 37 of 63 [58.7%], Cbd: 26 of 58 [44.8%], P = .13). All components of ESAS improved (fell) over time with no difference between arms. The median dose of participant-selected CBD was 400 mg per day with no correlation with opioid dose. There was no detectable effect of CBD on quality of life, depression, or anxiety. Adverse events did not differ significantly between arms apart from dyspnea that was more common with CBD. Most participants reported feeling better or much better at days 14 (53% CBD and 65% placebo) and 28 (70% CBD and 64% placebo). Conclusion: CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.