People living with chronic pain should be offered a trial of non-inhaled medical cannabis or cannabinoids if standard care is not sufficient, according to an international panel of experts. Their clinical guidelines for medical cannabis have been published in the British Medical Journal.
The panel noted that this was a “weak recommendation” because of the slim balance between benefits and harms, and the high value placed on small to very small improvements in pain relief. The researchers reviewed three dozen medical cannabis studies, as part of the BMJ’s Rapid Recommendations initiative.
The researchers are from, among others: McMaster University and the University of Toronto in Canada; Katholieke Universiteiti Leuven in Belgium; Sichuan University in China; Oslo University Hospital and the Innlandet Hospital Trust in Norway; University Hospitals of Geneva and University of Geneva in Switzerland; Monash University in Australia; and Harvard Medical School and Indiana University in the United States.
Stat reported that while medical cannabis might be a helpful therapy for some people with chronic pain, it is unlikely to benefit most. The guidelines say that there is not enough evidence that medical cannabis products help most patients suffering from chronic pain, so they should not be widely recommended.
“When we look at the overall evidence for therapeutic cannabis products, the benefits are quite modest,” said lead author Jason Busse, associate director of McMaster University’s Michael G DeGroote Centre for Medicinal Cannabis Research in Ontario.
Although medical cannabis has been legalised in most American states and many other countries, there has been little guidance for doctors regarding when and how it is appropriate to use, especially for chronic pain, continued Stat.
Busse and his team set out to fill that gap, but found a limited pool of studies that met their criteria because of federal restrictions that make it difficult to research medical uses of cannabis. The guidelines do not recommend the medical use of smoked or vaped marijuana.
In analysing the available research, Busse’s team found that only small percentages of participants reported “an important improvement” in chronic pain, physical function, or sleep quality while taking oral or topical cannabis treatments.
“So medical cannabis is not likely to be a panacea. It is not likely to work for the majority of individuals who live with chronic pain. We do have evidence that it does appear to provide important benefits for a minority of individuals,” said Busse, who is also a chiropractic doctor.
BMJ editorial
Methodological and ethical problems in the trials review limited the level of certainty in the evidence underpinning Busse and colleagues’ recommendations, said an editorial published in the BMJ, by Edeltraut Kröger and Clermont E Dionne of Hôpital St-Sacrement and Université Laval in Québec, Canada. “It may be time for more inclusive recommendations,” they wrote, and urged caution.
Still, the editorial continued later: “This new patient centred guidance can improve shared decision-making: clinicians should emphasise the harms associated with vaping or smoking cannabis and, as recommended by other guidelines, suggest products with known compositions such as nabilone or nabiximols, discourage self-medication, and pay particular attention to vulnerable populations.
“Increased pharmacovigilance of all cannabis use remains a priority, along with an ambitious programme of rigorous research on the short and long term effectiveness and safety of individual cannabis products for specific types of chronic pain.”
Study details
Medical cannabis or cannabinoids for chronic pain: A clinical practice guideline
Jason W Busse, Patrick Vankrunkelsven, Linan Zeng, Anja Fog Heen, Arnaud Merglen, Fiona Campbell, Lars-Petter Granan, Bert Aertgeerts, Rachelle Buchbinder, Matteo Coen, David Juurlink, Caroline Samer, Reed A C Siemieniuk, Nimisha Kumar, Lynn Cooper, John Brown, Lyubov Lytvyn, Dena Zeraatkar, Li Wang, Gordon H Guyatt, Per O Vandvik andThomas Agoritsas.
Author affiliations
Canada: McMaster University, University of Toronto, Chronic Pain Centre of Excellence for Canadian Veterans, Sunnybrook Health Sciences Centre and the Canadian Injured Workers’ Alliance. Belgium: Belgian Centre for Evidence Based Medicine (CEBAM) and the Katholieke Universiteiti Leuven. China: West China Second University Hospital at Sichuan University. Norway: Innlandet Hospital Trust, Gjøvik, Oslo University Hospital. Switzerland: University Hospitals of Geneva and the University of Geneva. Australia: Monash University in Melbourne. United States: Harvard Medical School and Indiana University.
Published in BMJ on 9 September 2021.
Abstract
Clinical question
What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes?
Current practice
Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries.
Recommendation
The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain.
How this guideline was created
An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective.
The evidence
This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain.
Understanding the recommendation
The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self-reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self-limited and transient harms.
Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation.
BMJ Editorial
Medical cannabis for chronic pain
Edeltraut Kröger and Clermont E Dionne
Author affiliations
Hôpital St-Sacrement and Université Laval in Québec, Canada.
Published in BMJ on 9 September 2021.
Patient centred guidance recommends a trial of treatment
Patients with persistent pain continue to search for new therapeutic options and often perceive cannabis as a worthwhile alternative. Clinicians need guidance on this option to inform shared decision-making with patients.
The linked clinical guidance by Busse and colleagues was developed for this purpose and comes from an international panel combining several disciplines, specialties, and patient groups.
The new guidance is based on a systematic review of the effectiveness of medical cannabis for chronic pain, offers an online tool, and has the potential to fill a critical gap in information for decision-making, enabling more inclusive management of chronic pain.
The guidance offers a weak recommendation for a trial of non-inhaled medical cannabis for the treatment of chronic pain. Its summary indicates moderate evidence of a clinically important decrease in pain for a small to very small proportion of patients.
The recommendation for a trial of treatment is based on two meta-analyses of randomised trials within the systematic review: first, a meta-analysis of 27 randomised controlled trials finding an increase in the proportion of patients reporting an improvement in pain of at least 1 cm on a 10 cm visual analogue scale (although a minimum reduction of 1.5 cm is considered clinically relevant); second, a meta-analysis of 10 placebo controlled trials reporting a 7% increase in the proportion of people reporting at least a 30% reduction in pain in favour of cannabis compared with placebo.
Methodological and ethical problems in these trials limited the level of certainty in the evidence underpinning Busse and colleagues’ recommendations. They include follow-up periods of less than six months (very short for chronic conditions), small sample sizes, funding by industry, and use of different outcome measures that complicate comparisons.
The new guidance adds to previous guidance by combining evidence from trials of medical cannabis and cannabinoids in patients with all types of chronic pain. This is important, since only a minority of included studies evaluated these agents in the management of chronic musculoskeletal pain, which is common, difficult to treat, increases with age, and has given rise to problematic prescribing of opiates.
Evidence on the effectiveness of medical cannabis against chronic musculoskeletal pain is rare, and several previous guidelines did not recommend cannabis for this indication. However, in its most recent edition (11th) the International Classification of Diseases defines three major types of chronic pain: neuropathic, nociplastic, and nociceptive pain.
Busse and colleagues found no significant differences in the effects of medical cannabis on neuropathic pain and the other two subtypes, and thus recommended non inhaled medical cannabis for all chronic pain, regardless of origin.
It may be time for more inclusive recommendations. However, given the high prevalence of chronic musculoskeletal pain and the frequent use of self-medication by patients, some caution may be warranted.
First, self-medication might lead to increased use of cannabis products with a worse risk-benefit profile (higher doses or a higher concentration of tetrahydrocannabinol, for example) than the products recommended by Busse and colleagues. Also, since inhalation leads to a faster and more powerful pharmacological effect than other routes of administration, patients may prefer inhaled cannabis products despite their potential for harm.
Access to optimal pain treatment is often limited, which could lead to a widespread and problematic use of cannabis. In many countries, nabilone and nabiximols are the only regulated cannabis medications. Other products available for self medication have uncertain compositions that may often vary between batches, making accurate dosing challenging.
The frontier between recreational and medical use of cannabis and cannabinoids is not always clearly drawn. Teenagers and younger adults particularly, may self medicate with recreational cannabis or consider a “medically recommended” substance as safe, potentially putting them at increased risk of neurological or psychiatric adverse events.
Although the review underpinning Busse and colleagues’ guidance found no evidence linking psychosis to the use of medical cannabis, knowledge of the effects of cannabis products on the young brain is just emerging. Researchers have observed, for example, that simultaneous use of recreational cannabis and alcohol increases the potential for addiction.
More widespread use of cannabis products for chronic pain could mean that “vulnerable populations…may experience novel toxic effects”. Finally, long term harms of new treatments often take years to emerge, including the dependency associated with use of opiates for chronic pain.
This new patient centred guidance can improve shared decision making: clinicians should emphasise the harms associated with vaping or smoking cannabis and, as recommended by other guidelines, suggest products with known compositions such as nabilone or nabiximols, discourage self medication, and pay particular attention to vulnerable populations.
Increased pharmacovigilance of all cannabis use remains a priority, along with an ambitious programme of rigorous research on the short and long term effectiveness and safety of individual cannabis products for specific types of chronic pain.
BMJ editorial – Medical cannabis for chronic pain (Open access)
See also from the MedicalBrief archives
Patients hopeful for France's medical cannabis experiment
Doctors still reluctant to prescribe medical cannabis – Canadian study
Medical cannabis in SA: Weighing the evidence
Medical cannabis provides symptom relief for a myriad of complaints
Medical cannabis cuts chronic pain in the elderly without adverse effects