The CANBACK Trial: a Randomised, Controlled Clinical Trial of Oral Cannabidiol for People Presenting to the Emergency Department with Acute Low Back Pain
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Research The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain Bronwyn Bebee1, David M Taylor1,2 , Elyssia Bourke1, Kimberley Pollack1, Lian Foster1, Michael Ching1, Anselm Wong1,2,3,4 Abstract The known: Low back pain is common among patients presenting to emergency departments. The short and long term efficacy of Objective: To assess the analgesic efficacy and safety of single- standard pharmaceutical interventions (paracetamol, non- steroidal dose oral cannabidiol (CBD) as an adjunct to standard care for anti- inflammatory drugs, opioids) is poor. Cannabidiol has anti- patients presenting to an emergency department with acute low inflammatory and analgesic properties, but its effect on acute low back pain. back pain has not been investigated. Design: Randomised, double blinded, placebo- controlled clinical trial. The new: Single- dose oral cannabidiol (400 mg) did not reduce pain scores in patients who presented to an emergency Setting: The tertiary emergency department of Austin Hospital, department with acute, non- traumatic low back pain. Melbourne. The implications: Cannabidiol does not reduce pain or hospital Participants: Patients who presented with acute, non- traumatic length of stay for people seeking help at a hospital emergency low back pain between 21 May 2018 and 13 June 2019. department for acute low back pain. Intervention: One hundred eligible patients were randomised to receiving 400 mg CBD or placebo in addition to standard emergency department analgesic medication. ow back pain is the most common musculoskeletal symp- Main outcome measures: Pain score two hours after tom among people visiting emergency departments, and administration of study agent, on a verbal numerical pain scale it is one of the top five most frequent complaints in emer- (range, 0‒ 10). Secondary outcomes were length of stay, need for L 1 gency medicine. A systematic review of 21 studies under- rescue analgesia, and adverse events. taken during 2000– 2016 in 12 countries found that low back Results: The median age of the 100 participants was 47 years (IQR, pain was consistently among the most frequent complaints in 34‒ 60 years); 44 were women. Mean pain scores at two hours were emergency medicine.2 Despite numerous studies and recom- similar for the CBD (6.2 points; 95% CI, 5.5– 6.9 points) and placebo mendations, a recent systematic review found that the utility groups (5.8 points; 95% CI, 5.1– 6.6 points; absolute difference, – 0.3 of standard pharmacological treatments for acute back pain points; 95% CI, – 1.3 to 0.6 points). The median length of stay was is limited.3 Accepted class II evidence indicates that patient 9.0 hours (IQR, 7.4‒ 12 hours) for the CBD group and 8.5 hours (IQR, 6.5‒ 21 hours) for the placebo group. Oxycodone use during the four education, superficial heat, paracetamol, non- steroidal anti- hours preceding and the four hours after receiving CBD or placebo inflammatory drugs, and the limited use of skeletal muscle was similar for the two groups, as were reported side effects. relaxants and opioids can be beneficial.1 It is reported that Conclusion: CBD was not superior to placebo as an adjunct emergency physicians often choose opioid therapy, includ- 4 medication for relieving acute non- traumatic low back pain in the ing 61% in a large American national sample and 70% in an emergency department. Australian study.5 However, medical therapy for low back pain Trial registration: Australian New Zealand Clinical Trials Registry, is of modest benefit. ACTRN12618000487213 (prospective). Cannabidiol (CBD) is the major non- psychotropic phytocan- nabinoid in Cannabis sativa (up to 40% of extracted alkaloids).6 Unlike most cannabinoids, including tetrahydrocannabinol Methods (THC), CBD does not have psychomotor or cognitive effects, and 6 its safety profile is good. CBD has attracted increasing medical The CANBACK trial was a single centre, randomised, double interest because of its anxiolytic, anti- inflammatory, anti- emetic, blinded, placebo- controlled clinical trial. Adults with acute, non- 6- 9 anti- epileptic, and anti- psychotic effects. It has been approved traumatic low back pain who presented to the Austin Hospital 10 in several countries for the treatment of neuropathic pain. The emergency department (Melbourne) during 21 May 2018 – 13 most frequently reported side effects of acute ingestion of CBD June 2019 were recruited. The Austin Hospital tertiary emer- are dizziness or drowsiness, itching or rash, headache, abdomi- gency department treats 90 000 patients each year, and offers a 9,11 nal discomfort, nausea, and vomiting or diarrhoea. Although wide range of clinical services. The trial was registered with the CBD and its analogues may be beneficial for reducing pain Australian New Zealand Clinical Trials Registry on 4 April 2018 caused by inflammation, its utility for treating acute low back (ACTRN12618000487213). pain has not been assessed.11 Participants 3 May 2021 The objective of our study was to compare the analgesic effect ▪ ) 8 and safety of single oral administration of CBD as an adjunct to Patients with acute low back pain were identified by the study ( standard care for patients who presented to an emergency de- investigators and clinical staff (medical and nursing) working in 214 partment with acute, non- traumatic low back pain, with those the triage and fast track areas of the emergency department, and MJA of a placebo. were managed in the short stay unit. Participants were provided 370 1 Austin Health, Melbourne, VIC. 2 University of Melbourne, Melbourne, VIC. 3 Victorian Poisons Information Centre, Austin Hospital, Melbourne, VIC. 4 Monash University, Melbourne, VIC. [email protected] ▪ doi: 10.5694/mja2.51014 ▪ See Editorial (Hayes). Research with a brief verbal description of the study and asked for written informed consent prior to enrolment. 1 CONSORT flow diagram of the CANBACK trial of oral cannabidiol for Analgesic medications used during the 24 hours people presenting to the emergency department with acute low back preceding presentation, as reported by participants, pain were recorded in our data sheet. We included people aged 18 years or more who pre- sented with acute non- traumatic low back pain — that is, pain and discomfort localised below the cos- tal margin and above the inferior gluteal folds, as assessed by the treating physician — of less than 30 days’ duration. This definition included people with histories of low back pain. We excluded people who reported using cannabis or CBD in the preceding seven days, those with abnormal neurological ex- amination findings (apart from subjective sensory changes), fever (exceeding 37.6°C), a history of malig- nancy, or a non- musculoskeletal cause of back pain, and women who were pregnant (urinary β- human chorionic gonadotropin testing of all women under 60 years of age). Intervention Most participants received standard emergency department drug treatment for low back pain; that is, 1000 mg paracetamol and 400 mg ibuprofen per os. However, treatment could be varied according to the that there were no serious adverse events, and that its phar- patient’s recent drug use and their tolerance of non- steroidal macokinetic properties were not significantly affected by anti- inflammatory drugs. Patients then received either the co- administration with fentanyl; peak clinical effect was ob- placebo (control group) or CBD (intervention group) (online served 1– 2 hours after administration of 400 mg CBD, and Supporting Information). CBD (> 99.9% synthetic) and pla- plasma concentrations were similar at two hours for both dose cebo were purchased as colour- matched medications from GD levels.9 We therefore expected that 400 mg CBD would have a Pharma (South Australia). The hospital pharmacy supplied measurable effect. 400 mg CBD in 4 mL medium chain triglyceride [MCT] oil) and placebo (4 mL MCT oil) as single oral syringe doses. Primary and secondary outcomes Pain scores — on a verbal numerical rating scale, ranging from The primary outcome measure was verbal numerical pain score 0 (no pain) to 10 (worst pain ever) — were recorded at triage, at (range, 0– 10) two hours after administration of CBD or placebo. 0, 30, 60, 90, and 120 minutes after drug administration, and at Secondary outcome measures were emergency department discharge from the emergency department. length of stay (including in the short stay unit), need for rescue analgesia, and any adverse event. Oxycodone (5 mg every 6 hours) was administered after 120 min- utes if pain was not adequately managed, and the emergency de- partment doctor could administer rescue analgesia (oxycodone) 2 Baseline demographic and clinical characteristics of at any time if they deemed it clinically indicated. participants in the CANBACK trial Patients were monitored in the emergency department short stay Cannabidiol unit for at least three hours after administration of the study group Placebo group agent and until pain was adequately controlled (ie, they could move safely, with oral analgesic medication as needed). Number of participants 50 50 Age (years), median (IQR) 52 (41– 59) 42 (31– 60) Data were collected on paper forms and transferred to a secured electronic Excel spreadsheet (Microsoft). Basic demographic in- Sex (women) 22 22 formation was extracted from the electronic hospital database Pain score at triage, mean (SD) 7.1 (2.5) 7.4 (2.1) (Cerner). Pain duration before presentation