To determine whether cannabidiol (CBD) oil can improve symptom distress in patients with advanced cancer receiving palliative care.

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.

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).

CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.

CONTEXT

Key Objective

The use of cannabis for therapeutic benefit has risen exponentially over the past few years with strong public belief in its benefit. This is despite very limited evidence of benefit and no clear guidance around which cannabinoid or combination to use for which indication and at what dose. This trial aimed to determine whether cannabidiol (CBD), a key component of cannabis, resulted in better symptom control in patients with advanced cancer than standard palliative care.

Knowledge Generated

CBD was not better than placebo in reducing symptom burden in patients with cancer receiving standard palliative care. Although well tolerated, it did not improve individual symptoms, depression/anxiety, and quality of life or reduce opioid requirements.

Relevance (S.B. Wheeler)

Given the large amount of public focus and funds increasingly spent on CBD products, CBD may not add value in reducing symptoms for patients with advanced cancer beyond standard palliative care.*

*Relevance section written by JCO Associate Editor Stephanie B. Wheeler, PhD, MPH.

Presented at the Australia New Zealand Society of Palliative Medicine (ANZSPM), Canberra ACT, Australia, September 2022.

Supported by the Commonwealth of Australia—Medical Research Future Fund—Grant No. APP1152232—commencing June 2018.

Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN 126180001220257, prospective registration July 20, 2018.

Individual non-reidentifiable participant data collected during the trial (including data dictionaries), the study protocol, statistical analysis plan, analytic code, and clinical study report will be available immediately following publication with no end date, on request to lead authors by researchers whose proposed use of the data has been approved by the DSMC overseeing the Mater Cannabis Research program to achieve the aims of a Mater Research DSMC–approved proposal and to the company supplying the trial product (as per agreed contract), but no other for-profit organization.

Conception and design: Janet Hardy, Phillip Good

Administrative support: Georgie Huggett

Collection and assembly of data: Janet Hardy, Georgie Huggett, Alison Kearney, Taylan Gurgenci, Phillip Good

Data analysis and interpretation: Janet Hardy, Ristan Greer, Taylan Gurgenci, Phillip Good

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Janet Hardy

Research Funding: GD Pharma Ltd (Inst)

Phillip Good

Research Funding: GD Pharma (Inst)

No other potential conflicts of interest were reported.