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Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials
  1. Aidan Leonard McParland1,
  2. Anuj Bhatia2,3,
  3. John Matelski4,
  4. Chenchen Tian3,
  5. Calvin Diep3,
  6. Hance Clarke2,3,
  7. Daniel Kapustin5,
  8. Aditya Triveda6,
  9. Richard Brull2,3 and
  10. Mandeep Singh2,3
  1. 1Department of Emergency Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
  2. 2Department of Anesthesia and Pain Management, University Health Network, Toronto, Ontario, Canada
  3. 3Department of Anesthesiology and Pain Management, University of Toronto, Toronto, Ontario, Canada
  4. 4Biostatistics Research Unit, University Health Network, Toronto, Ontario, Canada
  5. 5Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  6. 6School of Graduate Studies, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Mandeep Singh, Anesthesiology and Pain Management, Toronto Western Hospital, Toronto, Canada; mandeep.singh{at}


Background Chronic neuropathic pain is often debilitating and can have a significant impact on sleep health and quality of life. There is limited information on the impact of cannabinoids on sleep health when treating neuropathic pain.

Objective The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain intensity, and patient impression of treatment efficacy in patients with neuropathic pain.

Evidence review Nine available medical literature databases were searched for randomized controlled trials comparing synthetic and natural cannabinoids to placebo in patients with neuropathic pain syndromes. Data on validated tools for sleep quality, pain intensity, patients’ global impression of change (PGIC), and incidence of adverse effects of cannabinoids were extracted and synthesized.

Findings Of the 3491 studies screened, eight randomized controlled trials satisfied the inclusion criteria for this review. Analyses were performed using R -4.1.2. using the metafor package and are interpreted using alpha=0.05 as the threshold for statistical significance. Validated measures for sleep health were not used in most studies. Meta-analysis of data from six studies showed that cannabinoids were associated with a significant improvement in sleep quality (standardized mean difference (SMD): 0.40; 95% CI: 0.19 to −0.61, 95% prediction interval (PI): −0.12 to 0.88, p-value=0.002, I2=55.26, τ2=0.05, Q-statistic=16.72, GRADE: moderate certainty). Meta-analysis of data from eight studies showed a significant reduction in daily pain scores in the cannabinoid (CB) group (SMD: −0.55, 95% CI:−0.69 to −0.19, 95% PI: −1.51 to 0.39, p=0.003, I2=82.49, τ2=0.20, Q-statistic=47.69, GRADE: moderate certainty). However, sleep health and analgesic benefits were associated with a higher likelihood of experiencing daytime somnolence, nausea, and dizziness.

Conclusions Cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and PGIC. More research is needed to comprehensively evaluate the impact of cannabinoids on sleep health and analgesic efficacy.

PROSPERO registration number CRD42017074255.

  • pain management
  • chronic pain
  • clinical pain
  • neuralgia
  • peripheral nerve injuries

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  • Twitter @DrAnujBhatia, @calvdiep, @drhaclarke

  • Contributors ALM, AB, DK, AT, MS reviewed the literature, designed the protocol, performed overview of data collection, synthesized literature, and wrote the manuscript. HC, CD, RB, JM reviewed the literature, and wrote the manuscript. JM, MS, and ALM performed statistical analysis. All authors had a significant role in reviewing and formatting the manuscript.

  • Funding Departmental funds were used for the conducted for this study. MS, AB, RB, and HC are supported by the Merit Awards program of Department of Anesthesia and Pain Medicine, University of Toronto. MS is also supported by the Canadian Anesthesiologists' Society Career Scientist Award. CD is supported by the Clinician Investigator Program, Department of Anesthesia and Pain Medicine, University of Toronto.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.