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Practice Rapid Recommendations

Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline

BMJ 2021; 374 doi: https://doi.org/10.1136/bmj.n2040 (Published 09 September 2021) Cite this as: BMJ 2021;374:n2040

Visual summary of recommendation

Interventions compared or Cannabis Standard care plus a trial of non-inhaled medicalcannabis or cannabinoids Standard care No trial of medical cannabisor cannaninoids
Population This recommendation applies only to people with these characteristics: All patients living with moderate to severe chronic pain Applies to people with: Cancer and non-cancer pain May or may not apply to: Paediatric populations Does not apply to: Inhaled medical cannabis Recreational cannabis Patients receiving end of life care Veterans Patients with concurrent mental illness Patients receiving disability benefits or involved in litigation Neuropathic pain, nociceptive pain, and nociplastic pain
Recommendation
Standard careCannabisorPeople living with chroniccancer or non-cancer painIf standard care is not sufficient, we suggestoffering a trial of non-inhaled medical cannabisor cannabinoidsStrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Evidence profile

Favours standard careFavours cannabisNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
Potential benefits
1 to 4 monthsEvents per 1000 peopleEvidence quality

Reduction in pain100 more520620ModerateMore

Based on data from 3939 patients in 27 studiesUse of medical cannabis or cannabinoidsprobably results in a small increase inthe proportion of patients experiencingan important reduction in painMID1cmThe “minimally important difference” forpatients was defined as an improvementof 1 cm on a 10 cm visual analogue scaleModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencySeriousPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Improved physical function40 more280320HighMore

Based on data from 2425 patients in 15 studiesUse of medical cannabis or cannabinoidsresults in a very small increase in theproportion of patients experiencing animportant improvement in physicalfunctioningMID10The “minimally important difference” forpatients was defined as an improvementof 10 points on a 0-100 point SF-36physical functioning subscaleHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Improved emotional functionNo important difference310330HighMore

Based on data from 2115 patients in 10 studiesUse of medical cannabis or cannabinoidsdoes not improve emotional functioningMID10The “minimally important difference” forpatients was defined as an improvementof 10 points on a 0-100 point SF-36emotional functioning subscaleHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
1 to 3.5 monthsEvents per 1000 peopleEvidence quality

Improved role functionNo important difference410410HighMore

Based on data from 1128 patients in 7 studiesUse of medical cannabis or cannabinoidsdoes not improve role functioningMID10The “minimally important difference” forpatients was defined as an improvementof 10 points on a 0-100 point SF-36physical role functioning subscaleHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Improved social functionNo important difference390380HighMore

Based on data from 1405 patients in 8 studiesUse of medical cannabis or cannabinoidsdoes not improve social functioningMID10The “minimally important difference” forpatients was defined as an improvementof 10 points on a 0-100 point SF-36social role functioning subscaleHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
1.3 to 3.5 monthsEvents per 1000 peopleEvidence quality

Improved sleep quality60 more480540HighMore

Based on data from 2652 patients in 9 studiesUse of medical cannabis or cannabinoidsresults in a small increase in theproportion of patients experiencingimproved sleep qualityMID1cmThe “minimally important difference” forpatients was defined as an improvementof 1 cm on a 10 cm visual analogue scaleHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
Potential short term harms
1.3 to 3.5 monthsEvents per 1000 peopleEvidence quality

Cognitive impairment20 fewer1030ModerateMore

Based on data from 1033 patients in 5 studiesUse of medical cannabis or cannabinoidsprobably results in a small increase inthe proportion of patients experiencingcognitive impairmentModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
1 to 3.5 monthsEvents per 1000 peopleEvidence quality

Drowsiness50 fewer4090ModerateMore

Based on data from 2505 patients in 15 studiesUse of medical cannabis or cannabinoidsprobably results in a small increase inthe proportion of patients experiencingdrowsinessModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
1 to 4 monthsEvents per 1000 peopleEvidence quality

Impaired attention30 fewer1040ModerateMore

Based on data from 895 patients in 7 studiesUse of medical cannabis or cannabinoidsprobably results in a small increase inthe proportion of patients experiencingimpaired attentionModerateGRADE rating,because of:Risk of biasNo serious concernsImprecisionSeriousIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes
Patient decision aids

Individual considerations

Key practical issues The weak recommendation 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 Values and preferences Cannabis Standard care Therapeutic trials should start with low dose, non-inhaled cannabidiol products, gradually increasing the dose and tetrahydrocannabinol level depending on clinical response and tolerability Prior cannabis experience should be considered, and adverse events should be carefully monitored For younger or adolescent patients, cannabidiol-predominant preparations should be preferred, because of uncertain effects of tetrahydrocannabinol on neurocognitive development Patients should avoid driving or operating machinery while starting or changing dose of medical cannabis Women contemplating pregnancy, pregnant women, or women who are breast feeding should be encouraged to discontinue use of medical cannabis in favour of alternative therapy No additional practical issues

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Disclaimer: This infographic is not a validated clinical decision aid. This information is provided without any representations, conditions or warranties that it is accurate or up to date. BMJ and its licensors assume no responsibility for any aspect of treatment administered with the aid of this information. Any reliance placed on this information is strictly at the user's own risk. For the full disclaimer wording see BMJ's terms and conditions: https://www.bmj.com/company/legal-information/

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Linked Research

Medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised clinical trials

Linked Editorial

Medical cannabis for chronic pain
  1. Jason W Busse, chiropractor, methods co-chair, associate professor1234,
  2. Patrick Vankrunkelsven, general practitioner, clinical chair56,
  3. Linan Zeng, methodologist27,
  4. Anja Fog Heen, medical resident8,
  5. Arnaud Merglen, paediatrician9,
  6. Fiona Campbell, anaesthesiologist, professor10,
  7. Lars-Petter Granan, physiatrist, associate professor11,
  8. Bert Aertgeerts, general practitioner, professor1213,
  9. Rachelle Buchbinder, rheumatologist, professor1415,
  10. Matteo Coen, general internist1617,
  11. David Juurlink, general internist, professor1819,
  12. Caroline Samer, pharmacologist, assistant professor2021,
  13. Reed A C Siemieniuk, general internist, methodologist2,
  14. Nimisha Kumar, medical student, patient representative22,
  15. Lynn Cooper, patient representative23,
  16. John Brown, patient representative4,
  17. Lyubov Lytvyn, patient liaison expert2,
  18. Dena Zeraatkar, methodologist224,
  19. Li Wang, assistant professor23,
  20. Gordon H Guyatt, general internist, distinguished professor2,
  21. Per O Vandvik, general internist, associate professor8,
  22. Thomas Agoritsas, general internist, methods co-chair, assistant professor225
  1. 1Michael G DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, ON, Canada
  2. 2Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
  3. 3Department of Anesthesia, McMaster University, Hamilton, ON, Canada
  4. 4Chronic Pain Centre of Excellence for Canadian Veterans, Hamilton, ON, Canada
  5. 5Belgian Centre for Evidence Based Medicine (CEBAM), Leuven, Belgium
  6. 6Department of Public Health and Primary Care, Katholieke Universiteiti Leuven, Leuven, Belgium
  7. 7Pharmacy Department/Evidence-based Pharmacy Centre, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
  8. 8Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway
  9. 9Division of General Pediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland
  10. 10Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada
  11. 11Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
  12. 12Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven
  13. 13CEBAM, Belgian Centre for Evidence-Based Medicine, Cochrane Belgium
  14. 14Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
  15. 15Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia
  16. 16Division of General Internal Medicine, Department of Medicine, Geneva University Hospital, Geneva, Switzerland
  17. 17Unit of Development and Research in Medical Education, Faculty of Medicine, University of Geneva, Geneva, Switzerland
  18. 18Division of Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
  19. 19Departments of Medicine and Pediatrics, University of Toronto, Toronto, ON, Canada
  20. 20Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals
  21. 21Faculty of Medicine, University of Geneva, Switzerland
  22. 22Indiana University School of Medicine, Indianapolis, IN, USA
  23. 23Canadian Injured Workers’ Alliance, Thunder Bay, ON, Canada
  24. 24Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
  25. 25Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211, Geneva, Switzerland
  1. Correspondence to: J W Busse bussejw{at}mcmaster.ca

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.

Footnotes

  • This BMJ Rapid Recommendation article is one of a series that provides clinicians with trustworthy recommendations for potentially practice changing evidence. BMJ Rapid Recommendations represent a collaborative effort between the MAGIC group (http://magicproject.org/) and The BMJ. A summary is offered here and the full version including decision aids is on the MAGICapp (https://app.magicapp.org), in multilayered formats for all devices. Those reading and using these recommendations should consider individual patient circumstances, and their values and preferences and may want to use consultation decision aids in MAGICapp to facilitate shared decision making with patients. We encourage adaptation and contextualisation of our recommendations to local or other contexts. Those considering use or adaptation of content may go to MAGICapp to link or extract its content or contact The BMJ for permission to reuse content in this article.

  • Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 2. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Personal, professional, and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions.

  • Funding: The Michael G DeGroote Centre for Medicinal Cannabis Research funded the MAGIC Evidence Ecosystem Foundation to support the creation of this Rapid Recommendation. The central operating funding for the Michael G DeGroote Centre for Medicinal Cannabis Research is from a philanthropic gift to the Michael G DeGroote Initiative for Innovation in Healthcare. The centre receives no funding from industry.

  • Transparency: JWB affirms that the manuscript is an honest, accurate, and transparent account of the recommendation being reported; that no important aspects of the recommendation have been omitted; and that any discrepancies from the recommendation as planned (and, if relevant, registered) have been explained.

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