Lack of efficacy of cannabidiol for relieving back pain: time to re‐set expectations?

In the absence of evidence of benefit for acute low back pain, its over‐the‐counter availability should be reconsidered

Decades of opioid overuse can teach us valuable lessons about how we should handle medicinal cannabinoids, including cannabidiol (CBD). One major lesson is that access to medicines should not move ahead of scientific evidence. Over time, evidence that context is critical has accumulated: using opioids to treat acute pain and cancer pain, in the management of opioid dependency, and in palliative care can be justified. However, the indication creep from acute to chronic non‐cancer pain was unwarranted. Consequently, clinicians are sensitive to new pain medicines being made available without evidence of benefit, and the motivations for accelerated access have been questioned.1

Access in Australia to medicinal cannabinoids has moved ahead of the evidence. The Therapeutic Goods Administration (TGA) grants more than 6000 Special Access Scheme approvals for prescribing medicinal cannabinoids each month.2 It would be helpful if the TGA reported the types of cannabinoids authorised, a breakdown of indications, and all reported toxicity.

A recent systematic review concluded that there is insufficient evidence to support or oppose the use of cannabinoids for treating pain.3 This followed an Australian systematic review of cannabinoids for treating chronic non‐cancer pain4 which found that the number needed to treat for 30% pain reduction was 24 and the number needed to harm was six.

CBD has been touted as a special case, widely perceived by non‐clinicians as relatively non‐toxic.5 However, this is not consistent with clinical experience, particularly noting the potential for CBD‐related drug interactions.6 To practise safely, more evidence is needed about indications for CBD, individualised treatment requirements, and the implications of long term therapy. Although not known to cause psychosis, CBD clearly crosses the blood–brain barrier, as evidenced by its use for treating sleep problems, anxiety, and intractable childhood epilepsy.7

Where are we now in Australia? Following a 2020 Senate inquiry,8 and a submission to the TGA,9 CBD (at up to 150 mg/day for adults) was down‐scheduled from Schedule 4 (prescription medicine) to Schedule 3 (pharmacist only medicine) in December 2020.10 Neither clinical trial data supporting its efficacy at this dose for the variety of indications for which it might be used, nor safety information were available; known side effects were deemed to be non‐serious (drug interactions excluded). CBD is administered to children with epilepsy at up to 20 mg/kg per day, but dosing for adults is not usually weight‐based; it ranges in published studies from 0.6 to 50 mg/kg per day.11 For the conditions in which it is likely to be used by adults (epilepsy, chronic pain, drug dependency), several predictable but as yet unquantified drug interactions may have untoward effects, particularly if CBD is stopped and started suddenly.12 Quality trial data for a patient group likely to consider using CBD, as reported in this issue of the Journal,13 are therefore important for guiding clinical practice.

The CANBACK study13 was a randomised, double blinded, controlled trial in which Bebee and colleagues compared the analgesic efficacy and safety of single‐dose oral CBD as an adjunct to standard care with those of placebo in patients presenting to an emergency department with acute low back pain, a relevant and representative clinical group. As CBD was used as an adjunct to standard care, the approach would be easily translatable to practice. The authors found no difference between the CBD and placebo groups with respect to the primary outcome, verbal numerical pain score (range, 0–10) two hours after administration. Further, there were no differences in secondary outcomes; median lengths of emergency department stay were similar (important from the patient flow perspective), and oxycodone use during the four hours before and the four hours after receiving CBD or placebo was similar for the two groups, as were side effect rates and types.13

The investigators noted that the verbal numerical pain scale is widely used and accepted, but is not objective. A further limitation was the lack of pharmacokinetic data that would have clarified whether therapeutic blood concentrations were achieved. However, the dose chosen was nearly three times the upper limit of the permissible over‐the‐counter CBD dose. Dosing is often difficult for cannabinoid trials, as dose–response studies have not been undertaken. Clinicians base decisions on information adapted from other conditions or from toxicity studies in childhood epilepsy trials. The 400 mg dose selected was based on safety and toxicology data for humans,14 and on CBD studies assessing its therapeutic properties in children and adults that suggested peak blood concentration were reached at 1–2 hours, appropriate for emergency department care.

In conclusion, CANBACK is the largest clinical trial to have investigated CBD for treating acute low back pain. The rigorously designed study reflected real world management of this condition in the emergency department, and its findings provide helpful guidance for doctors, particularly as we have no quality evidence base for the efficacy and safety of CBD in the range of conditions for which its use is requested. The over‐the‐counter availability of CBD will make it difficult to restrict its use for treating acute low back pain, even though it is now known to be ineffective for this condition. We must acknowledge these data and reflect upon the perils of overly focusing on drugs for the treatment of pain.