LAUSR

This journal recently published a paper by Horsted et al. (2022) entitled ‘Safety and Efficacy of Cannabinoids to Danish Patients with Treatment Refractory Chronic Pain— A Retrospective Observational Realworld Study’. Eight hundred and twentysix patients with ‘refractory’ chronic pain, were prescribed oral cannabinoids consisting of either delta9tetrahydrocannabinol 14 (THC), cannabidiol (CBD) or their combination. Data on adverse effects, pain reduction, sleep quality and quality of life were collected roughly 2 and 4 months (median) following treatment initiation. Nearly twothirds of the patients were included in the first followup analyses and only a quarter in the second. An intentiontotreat (ITT) analysis of 826 eligible patients revealed clinically relevant pain reduction (NRS ≥30%) in 17% and 10% at the two followups or in 32% and 45% of 529 and 214 analysed patients, respectively, according to a perprotocol (PP) analysis. Perprotocol analyses also revealed improvement in sleep quality and in quality of life in ~50%. Adverse events were reported by 42% and 34% of the patients at the two followup time points and were mild to moderate in general. Although the medicinal use of cannabinoids continues to expand, ongoing attempts fail to provide clear evidence of their effectiveness and safety for pain. A considerable number of randomized controlled trials (RCTs) and subsequent systematic reviews and metaanalysis (SRMA) have not been translated into solid clinical evidence or practice guidance on cannabinoids for chronic pain (Eisenberg et al., 2022). To increase the foundation of evidence in such circumstances, GRADE (Grading of Recommendations Assessment, Development and Evaluation) allows to consider realworld observational studies if pointing to consistent and large effects. Indeed, several longterm observational studies on cannabinoids in chronic pain have been published and six of them were even included in a recent SRMA (Bialas et al., 2022). It concluded that: ‘within the context of observational studies— which should be regarded with caution— cannabisbased medications had positive effects on multiple symptoms for some chronic pain patients and were generally well tolerated and safe’. The percentage of patients achieving 30% pain relief in the Horsted et al. (2022) study, which ranges between 32%– 45% in the PP analysis and 10– 17% in the ITT, seems congruent with previous reports. For example, Bialas et al. (2022) reported of 38.3% of patients achieving the 30% target in all six included studies, and 20.5% after removing four studies for which an imputation method was used to calculate responder rates. The same is probably true for the improvement in secondary outcomes such as sleep and qualityoflife, and for the rates and types of reported adverse events. Hence, the authors concluded that ‘oral cannabinoid therapy seems to be safe and mildly effective in patients with chronic pain’ (Horsted et al., 2022) may strengthen what is already known, but is marginal in terms of added value. An additional major drawback of this and most other realworld observational studies