Efficacy, tolerability and safety of cannabinoids for management of pain in adult patients with multiple sclerosis: A systematic review and meta-analysis
1Pain Management, Diagnosis and Treatment, Pharmacological, Interventional and Other Techniques, Aretaieion University Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
2Musculoskeletal Health, Ippokration General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
DOI: 10.22514/sv.2021.157 Vol.17,Issue S1,September 2021 pp.10-10
Submitted: 26 August 2021 Accepted: 06 September 2021
Published: 15 September 2021
Objective: Conduction of a systematic review and meta-analysis to determine the clinical efficacy, tolerability and safety of cannabinoids in adults patients with multiple sclerosis and intractable pain.
Methods: Our review was performed according to the PRISMA guidelines. Pubmed, Scopus, Cochrane Library databases and ClinicalTrials.gov, EudraCT registries were searched for double-blind RCTs, involving adults with any form of multiple sclerosis and intractable pain. We included studies with cannabinoids of any type, dose or route of administration versus any control group. Risk of bias was assessed with Cochrane Risk of Bias 2 tool and certainty of evidence was rated according to GRADE approach. Review Manager 5.4 computer program was used to conduct our meta-analysis.
Results: 6 trials, including 798 patients, were analyzed. Cannabinoids were superior to placebo for reducing pain intensity with statistical significance [MD = –0.48 (–0.88 to –0.08)]. Instead, overall withdrawals and frequency of adverse events showed a statistically significant increase in the cannabinoid groups [RR = 1.63, (1.05 to 2.52), ΝΝΤΗ = 19 (8 to 200) and RR = 1.32 (1.12 to 1.55), ΝΝΤΗ = 6 (3 to 16) respectively]. No statistical significant difference has been found on serious adverse events frequency. Short-term trials with small size and studies investigating THC/CBD spray (up to 120 mg/120 mg per day), showed a significant reduction in pain (0.90 and 0.86 points on NRS 0–10 scale respectively).
Conclusions: Cannabinoids have never been administered as monotherapy and always administered by titration to treat intractable pain of various types in patients with multiple sclerosis. Our findings were based on a small number of trials and patients. Therefore certainty of evidence has been rated as moderate. Oromucosal spray THC/CBD (up to 120mg/120mg daily) is most likely to be used, in patients with multiple sclerosis and pain resistant to conventional analgesics, initially for short term treatment in future clinical practice.
Liapodimitris Dimitrios,Fotakis Aris. Efficacy, tolerability and safety of cannabinoids for management of pain in adult patients with multiple sclerosis: A systematic review and meta-analysis. Signa Vitae. 2021. 17(S1);10-10.
 Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. Journal of Clinical Epidemiology. 2011; 64: 380–382.
 Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions. John Wiley & Sons: Hoboken. 2019.
 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of Clinical Epidemiology. 2009; 62: e1–e34.
 Review Manager (RevMan) [Computer program]. Version 5.4.1, The Cochrane Collaboration, 2020
 Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. British Medical Journal. 2019; 366: l4898.
 Tacconelli E. Systematic reviews: CRD's guidance for undertaking reviews in health care. The Lancet Infectious Diseases. 2010; 10: 226.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.
IndexCopernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.
Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.
Scopus: CiteScore 0.5(2021) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.
Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.