Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of cannabidiol (CBD)

Abstract

BackgroundDespite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.Methods and designThis study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians.DiscussionA major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms.Trial registration numberALCTRN12618001220257 Registered 20/07/2018.

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

“…Medicinal cannabis and its secondary metabolites have garnered significant attention in recent years, and have been subject to extensive research and scrutiny [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. From a medicinal and pharmaceutical standpoint, nonpsychoactive phytocannabinoids—such as cannabidiol (CBD)—are the most potentially beneficial components of cannabis’ chemical space [ 2 , 8 ].…”

Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies

“…A double-blind, placebo-controlled, randomized clinical phase I trial has proven its safety and capability to relieve tumor-related adverse effects at a CBD concentration of 100 mg/mL, within a dose range of 50 mg to 600 mg per day, in 2 weeks. CBD improves both physical and psychological symptoms in patients with advanced cancer [ 138 ]. Another study focused on therapy for severe cancer-related side effects associated with chemotherapy, in which 177 patients were included who were experiencing unsatisfactory analgesic effects even during a standard chronic opioid titration phase.…”

Living with Metastatic Cancer: A Roadmap for Future Research

“…Ongoing research efforts are also exploring new opportunities for medical management of cancer-related distress and symptom burden. For example, emerging evidence suggests that a single high dose of psilocybin may produce lasting improvement in depression and anxiety in patients with terminal cancer [ 162 ], and cannabinoids are under investigation to reduce overall symptom burden among patients with advanced cancer [ 163 ]. Other studies mostly grounded in cognitive-behavioral therapy have sought to directly improve PROs including distress [ 164 , 165 , 166 , 167 , 168 , 169 ], quality of life [ 170 , 171 , 172 , 173 , 174 , 175 ], and side effects of metastatic cancer and its treatments [ 176 , 177 , 178 , 179 , 180 ].…”