Phase II, Double-blind, Placebo-controlled Trial of a Single Dose of Pharmaceutical, Herbal Cannabidiol to Manage Scan-related Anxiety in Women with Breast Cancer

Abstract: Background/Significance: One in four or five adults facing cancer suffers with clinical anxiety. Few advances in the pharmacologic management of acute anxiety—cancer-related or otherwise—have emerged in a half-century. The standard of care, benzodiazepines, carries myriad risks (e.g., confusion, dementia, hypersomnia, perceptual disturbances, amnesia, addiction, ataxia) that can be amplified in adults with cancer, who may be frail, elderly and on polypharmacy. Safer, effective alternatives are critically needed. Small, randomized trials outside of oncology suggests that cannabidiol (CBD), an herbal, non-intoxicating, non-habit-forming Cannabis sativa component, may possess anxiolytic effects. This study investigated a single 400 mg oral dose of CBD oil for cancer-related anxiety management.



Methods: In this single-institution, phase II, randomized, double-blind trial, women with metastatic breast cancer and baseline clinical anxiety (N=50) were randomized 1:1 to receive oral, Federal Drug Administration-approved (for an indication of pediatric epilepsy) CBD 400 mg versus placebo within 48 hours of an imaging study to assess tumor burden. The primary endpoint was a between arm comparison of change scores on the ‘Afraid’ subscale of the Visual Analog Mood Scale (VAMS) pre- and three (+/-1) hours post-study drug ingestion. Exploratory outcomes included between arm comparisons of anxiety levels three (+/-1) hours post-study drug ingestion; between arm comparisons of change scores on other VAMS subscales; safety; and feasibility.



Results: Fifty women completed the trial. The primary endpoint of VAMS_Afraid change score, although numerically greater in the CBD arm, was not significantly different between arms (CBD: -19.1; placebo: -15.0; p=0.37). The secondary outcome directly comparing anxiety levels between arms three hours post-study drug ingestion did show significantly lower VAMS_Afraid scores for those who received CBD as compared to controls (CBD: 51.5; placebo: 58.0; p=0.02). No grade 3 or 4 toxicities were reported, and the study proved feasible.



Discussion: Use of oral CBD prior to restaging scans in patients with metastatic breast cancer was safe and feasible. The study did not meet its primary endpoint comparing pre- versus post- anxiety change scores between study arms, possibly attributable to low power. However, three hours post study drug-ingestion, anxiety levels were significantly lower in the CBD arm as compared to controls.

Conclusion: Findings from this innovative, integrative medicine clinical drug trial established feasibility and safety of CBD for anxiety in a population with advanced breast cancer; and laid groundwork for a larger, more definitive trial testing efficacy of oral CBD 400 mg in reducing anxiety in women facing advanced breast cancer. Data from this study invites completion of a longitudinal trial, incorporating anxiety score trajectories on repeated in-the-moment measures, and use of wearable devices to objectively measure anxiety phenomenon. Such a study would allow the scientific community to truly assess whether this alternative therapy, which can clearly be used safely in a medically ill population, benefits adults with cancer facing acute anxiety.

Note: After conferring with ACLP conference staff that this is a possibility, Dr. Braun (senior author) hopes to co-present with first author of the manuscript to come and an early career research, Manan Nayak, PhD.

Presentation Eligibility: This research has never been published or presented; will be submitted to the American Society of Clinical Oncology's Journal of Clinical Oncology in the coming months. Dr. Braun would derive great satisfaction in presenting this data for the first time in her home professional society of ACLP.

Diversity, Equity, and Inclusion: *Senate Majority Leader, Chuck Schumer (D-NY), explained: “Marijuana laws have been one of the biggest examples of racial injustice.” African American men are 3.6x more likely than their Caucasian counterparts to be arrested for cannabis offenses.

*With an eye to justice and inclusivity, a unique design strength was at-home study procedures which facilitated participation of a socio-demographically and culturally diverse population.

*Dr. Manan Nayak, who will co-first author the manuscript to come, is a women-of-color in the sciences.